WorldWideScience

Sample records for rat aortic vascular

  1. A new iridoid and effect on the rat aortic vascular smooth muscle cell proliferation of isolated compounds from Buddleja officinalis.

    Science.gov (United States)

    Tai, Bui Huu; Nhiem, Nguyen Xuan; Quang, Tran Hong; Ngan, Nguyen Thi Thanh; Tung, Nguyen Huu; Kim, Yohan; Lee, Jung-Jin; Myung, Chang-Seon; Cuong, Nguyen Manh; Kim, Young Ho

    2011-06-01

    A new iridoid, named methylscutelloside (1) together with 19 known compounds belonging to the iridoids (2-4), monoterpenoids (5), flavonoids (6-8), triterpenoids (9-14), and phenylethanoids (15-20) were isolated from the flowers of Buddleja officinalis. Their chemical structures were elucidated on the basis of physicochemical properties, and by spectroscopic methods including 1D, 2D NMR, and MS. All isolated compounds were tested in vitro for their effects on the proliferation of rat aortic vascular smooth muscle cells (VSMCs). Among them, iridoids were the main active components and showed significant inhibitory effects on PDGF-BB-induced proliferation in rat aortic VSMCs. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Vascular Response of Ruthenium Tetraamines in Aortic Ring from Normotensive Rats

    Directory of Open Access Journals (Sweden)

    Ana Gabriela Conceição-Vertamatti

    2015-03-01

    Full Text Available Background: Ruthenium (Ru tetraamines are being increasingly used as nitric oxide (NO carriers. In this context, pharmacological studies have become highly relevant to better understand the mechanism of action involved. Objective: To evaluate the vascular response of the tetraamines trans-[RuII(NH34(Py(NO]3+, trans-[RuII(Cl(NO (cyclan](PF62, and trans-[RuII(NH34(4-acPy(NO]3+. Methods: Aortic rings were contracted with noradrenaline (10−6 M. After voltage stabilization, a single concentration (10−6 M of the compounds was added to the assay medium. The responses were recorded during 120 min. Vascular integrity was assessed functionally using acetylcholine at 10−6 M and sodium nitroprusside at 10−6 M as well as by histological examination. Results: Histological analysis confirmed the presence or absence of endothelial cells in those tissues. All tetraamine complexes altered the contractile response induced by norepinephrine, resulting in increased tone followed by relaxation. In rings with endothelium, the inhibition of endothelial NO caused a reduction of the contractile effect caused by pyridine NO. No significant responses were observed in rings with endothelium after treatment with cyclan NO. In contrast, in rings without endothelium, the inhibition of guanylate cyclase significantly reduced the contractile response caused by the pyridine NO and cyclan NO complexes, and both complexes caused a relaxing effect. Conclusion: The results indicate that the vascular effect of the evaluated complexes involved a decrease in the vascular tone induced by norepinephrine (10−6 M at the end of the incubation period in aortic rings with and without endothelium, indicating the slow release of NO from these complexes and suggesting that the ligands promoted chemical stability to the molecule. Moreover, we demonstrated that the association of Ru with NO is more stable when the ligands pyridine and cyclan are used in the formulation of the compound.

  3. Vascular Response of Ruthenium Tetraamines in Aortic Ring from Normotensive Rats

    Energy Technology Data Exchange (ETDEWEB)

    Conceição-Vertamatti, Ana Gabriela; Ramos, Luiz Alberto Ferreira [Universidade Estadual de Campinas (UNICAMP), São Paulo, SP (Brazil); Calandreli, Ivy; Chiba, Aline Nunes [Universidade de São Paulo (USP), Campus Ribeirão Preto, São Paulo, SP (Brazil); Franco, Douglas Wagner [Universidade de São Paulo (USP), Campus São Carlos, São Paulo, SP (Brazil); Tfouni, Elia [Universidade de São Paulo (USP), Campus Ribeirão Preto, São Paulo, SP (Brazil); Grassi-Kassisse, Dora Maria, E-mail: doramgk@unicamp.br [Universidade Estadual de Campinas (UNICAMP), São Paulo, SP (Brazil)

    2015-03-15

    Ruthenium (Ru) tetraamines are being increasingly used as nitric oxide (NO) carriers. In this context, pharmacological studies have become highly relevant to better understand the mechanism of action involved. To evaluate the vascular response of the tetraamines trans-[Ru{sup II}(NH{sub 3}){sub 4}(Py)(NO)]{sup 3+}, trans-[Ru{sup II}(Cl)(NO) (cyclan)](PF{sub 6}){sub 2}, and trans-[Ru{sup II}(NH{sub 3}){sub 4}(4-acPy)(NO)]{sup 3+}. Aortic rings were contracted with noradrenaline (10{sup −6} M). After voltage stabilization, a single concentration (10{sup −6} M) of the compounds was added to the assay medium. The responses were recorded during 120 min. Vascular integrity was assessed functionally using acetylcholine at 10{sup −6} M and sodium nitroprusside at 10{sup −6} M as well as by histological examination. Histological analysis confirmed the presence or absence of endothelial cells in those tissues. All tetraamine complexes altered the contractile response induced by norepinephrine, resulting in increased tone followed by relaxation. In rings with endothelium, the inhibition of endothelial NO caused a reduction of the contractile effect caused by pyridine NO. No significant responses were observed in rings with endothelium after treatment with cyclan NO. In contrast, in rings without endothelium, the inhibition of guanylate cyclase significantly reduced the contractile response caused by the pyridine NO and cyclan NO complexes, and both complexes caused a relaxing effect. The results indicate that the vascular effect of the evaluated complexes involved a decrease in the vascular tone induced by norepinephrine (10{sup −6} M) at the end of the incubation period in aortic rings with and without endothelium, indicating the slow release of NO from these complexes and suggesting that the ligands promoted chemical stability to the molecule. Moreover, we demonstrated that the association of Ru with NO is more stable when the ligands pyridine and cyclan are used

  4. Vascular Reactivity Concerning Orthosiphon stamineus Benth-Mediated Antihypertensive in Aortic Rings of Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Nurul Maizan Manshor

    2013-01-01

    Full Text Available Orthosiphon stamineus Benth has been traditionally used to treat hypertension. The study aimed to investigate the vascular reactivity of water extract (WOS and water : methanolic (1 : 1 extract (WMOS of Orthosiphon stamineus Benth and AT1 receptors blocker in the mechanisms of antihypertensive mediated by α1-adrenergic receptor and EDNO and PGI2 releases in the SHR aortic rings. SHR (230–280 g were divided into four groups: control, WOS, WMOS, and losartan. After being fed orally for 14 days, the aorta was harvested and subjected to PE (10−9 to 10−5 M and ACh (10−9 to 10−5 M with and without L-NAME (100 µM and indomethacin (10 µM, respectively. WOS, WMOS, and losartan significantly reduced the contractile responses to PE intact suggesting the importance of endothelium in vasorelaxation. Losartan significantly enhanced the ACh-induced vasorelaxation. L-NAME significantly inhibited the ACh-induced relaxation in all groups. Indomethacin enhanced ACh-induced vasorelaxation in WMOS. Collectively, Orthosiphon stamineus leaves extract reduced vasoconstriction responses by the alteration of α1-adrenergic and AT1 receptors activities. The involvement of EDNO releases was clearly observed in this plant. In WOS, PGI2 releases might not participate in the ACh-induced vasorelaxation. However, in WMOS, enhancement of vasorelaxation possibly due to continuous release of PGI2.

  5. Tetramethylpyrazine Protects against Hydrogen Peroxide-Provoked Endothelial Dysfunction in Isolated Rat Aortic Rings: Implications for Antioxidant Therapy of Vascular Diseases

    Directory of Open Access Journals (Sweden)

    Xiaojia Ni

    2014-01-01

    Full Text Available Background and Objectives. Oxidative stress can initiate endothelial dysfunction and atherosclerosis. This study evaluated whether tetramethylpyrazine (TMP, the predominant active ingredient in Rhizoma Ligustici Wallichii (chuanxiong, prevents endothelial dysfunction in a rat model of oxidative stress. Methods. Isolated rat aortic rings were pretreated with various drugs before the induction of endothelial dysfunction by hydrogen peroxide (H2O2. Changes in isometric tension were then measured in acetylcholine- (ACh- relaxed rings. Endothelial nitric oxide synthase (eNOS expression was evaluated in the rings by Western blotting, and superoxide anion (O2∙- content was assessed in primary rat aortic endothelial cells by dihydroethidium- (DHE- mediated fluorescence microscopy. Results. ACh-induced endothelium-dependent relaxation (EDR was disrupted by H2O2 in endothelium-intact aortic rings. H2O2-impaired relaxation was ameliorated by acute pretreatment with low concentrations of TMP, as well as by pretreatment with catalase and the NADPH oxidase inhibitors, apocynin and diphenyleneiodonium (DPI. TMP, apocynin, and DPI also reduced O2∙- accumulation in endothelial cells,but TMP failed to alter eNOS expression in aortic rings incubated with H2O2. Conclusions. TMP safeguards against oxidative stress-induced endothelial dysfunction, suggesting that the agent might find therapeutic utility in the management of vascular diseases. However, TMP’s role in inhibiting NADPH oxidase and its vascular-protective mechanism of action requires further investigation.

  6. Effects of High Glucose on Vascular Endothelial Growth Factor Synthesis and Secretion in Aortic Vascular Smooth Muscle Cells from Obese and Lean Zucker Rats

    Directory of Open Access Journals (Sweden)

    Mariella Trovati

    2012-07-01

    Full Text Available Type 1 diabetes is characterized by insulin deficiency, type 2 by both insulin deficiency and insulin resistance: in both conditions, hyperglycaemia is accompanied by an increased cardiovascular risk, due to increased atherosclerotic plaque formation/instabilization and impaired collateral vessel formation. An important factor in these phenomena is the Vascular Endothelial Growth Factor (VEGF, a molecule produced also by Vascular Smooth Muscle Cells (VSMC. We aimed at evaluating the role of high glucose on VEGF-A164 synthesis and secretion in VSMC from lean insulin-sensitive and obese insulin-resistant Zucker rats (LZR and OZR. In cultured aortic VSMC from LZR and OZR incubated for 24 h with D-glucose (5.5, 15 and 25 mM or with the osmotic controls L-glucose and mannitol, we measured VEGF-A164 synthesis (western, blotting and secretion (western blotting and ELISA. We observed that: (i D-glucose dose-dependently increases VEGF-A164 synthesis and secretion in VSMC from LZR and OZR (n = 6, ANOVA p = 0.002–0.0001; (ii all the effects of 15 and 25 mM D-glucose are attenuated in VSMC from OZR vs. LZR (p = 0.0001; (iii L-glucose and mannitol reproduce the VEGF-A164 modulation induced by D-glucose in VSMC from both LZR and OZR. Thus, glucose increases via an osmotic mechanism VEGF synthesis and secretion in VSMC, an effect attenuated in the presence of insulin resistance.

  7. Tetramethylpyrazine Protects against Hydrogen Peroxide-Provoked Endothelial Dysfunction in Isolated Rat Aortic Rings: Implications for Antioxidant Therapy of Vascular Diseases

    National Research Council Canada - National Science Library

    Ni, Xiaojia; Wong, Siu Ling; Wong, Chi Ming; Lau, Chi Wai; Shi, Xiaogeng; Cai, Yefeng; Huang, Yu

    2014-01-01

    ...), prevents endothelial dysfunction in a rat model of oxidative stress. Methods. Isolated rat aortic rings were pretreated with various drugs before the induction of endothelial dysfunction by hydrogen peroxide (H2O2...

  8. Demonstration of the histopathological and immunohistochemical effects of a novel hemostatic agent, ankaferd blood stopper, on vascular tissue in a rat aortic bleeding model

    Directory of Open Access Journals (Sweden)

    Gul Aylin

    2010-11-01

    Full Text Available Abstract Background Ankaferd Blood Stopper® (ABS is a folkloric medicinal plant extract used as a hemostatic agent in traditional Turkish medicine. This experimental study investigated the histopathological and immunohistochemical effects of ABS on vascular tissue in a rat model of aortic bleeding. Methods Four groups of 11 Wistar albino rats were used. The abdominal aortas of the rats were wounded; an ABS-soaked tampon was applied to rats in Groups 1 and 3, and a plain gauze tampon was applied to rats in Groups 2 and 4 until the bleeding stopped. The bleeding time was recorded. Immediately following sacrificing, the arteriotomy sites from Groups 1 and 2 were removed. The abdominal incisions in Groups 3 and 4 were closed following hemostasis. On Day 7 of the study, Group 3 and 4 rats were sacrificed and the abdominal aorta arteriotomy sites were removed for histopathological and immunohistochemical evaluation. Results The mean bleeding time in 15 animals in Groups 2 and 4 was 4.9 ± 0.6 s, and in 22 animals in Groups 1 and 3 was 3.1 ± 0.6 s. Distal aortic occlusion was not observed on either Day 1 or 7 in any group. Significantly more widespread and dense endothelial nitric oxide synthase (eNOS staining was observed in Group 1 animals than Group 2. On Days 1 and 7 after application of ABS, histopathological changes, consisting of necrosis, inflammation, and endothelial cell loss, in the rat abdominal aortas did not differ between Groups 1 and 2. The basophilic discoloration in the ABS group on the operation day was a result of a foreign body reaction and hemosiderin-loaded histiocyte accumulation, which occurred on Day 7. Conclusions In this study, hemostasis was successfully achieved with ABS in rat abdominal aortas. No histopathological change was found in the rat abdominal aortas between the ABS and control groups on Days 1 and 7. Further studies on the long-term effects of foreign body reactions and hemosiderin-loaded histiocyte

  9. Inhibitory role of reactive oxygen species in the differentiation of multipotent vascular stem cells into vascular smooth muscle cells in rats: a novel aspect of traditional culture of rat aortic smooth muscle cells.

    Science.gov (United States)

    Song, Haibo; Wang, Hui; Wu, Weiwei; Qi, Lei; Shao, Lei; Wang, Fang; Lai, Yimu; Leach, Desiree; Mathis, Bryan; Janicki, Joseph S; Wang, Xing Li; Tang, Dongqi; Cui, Taixing

    2015-10-01

    Proliferative or synthetic vascular smooth muscle cells (VSMCs) are widely accepted to be mainly derived from the dedifferentiation or phenotypic modulation of mature contractile VSMCs, i.e., a phenotype switch from a normally quiescent and contractile type into a proliferative or synthetic form. However, this theory has been challenged by recent evidence that synthetic VSMCs predominantly originate instead from media-derived multipotent vascular stem cells (MVSCs). To test these hypotheses further, we re-examine whether the conventional rat aortic SMC (RASMC) culture involves the VSMC differentiation of MVSCs or the dedifferentiation of mature VSMCs and the potential mechanism for controlling the synthetic phenotype of RASMCs. We enzymatically isolated RASMCs and cultured the cells in both a regular growth medium (RGM) and a stem cell growth medium (SCGM). Regardless of culture conditions, only a small portion of freshly isolated RASMCs attaches, survives and grows slowly during the first 7 days of primary culture, while expressing both SMC- and MVSC-specific markers. RGM-cultured cells undergo a process of synthetic SMC differentiation, whereas SCGM-cultured cells can be differentiated into not only synthetic SMCs but also other somatic cells. Notably, compared with the RGM-cultured differentiated RASMCs, the SCGM-cultured undifferentiated cells exhibit the phenotype of MVSCs and generate greater amounts of reactive oxygen species (ROS) that act as a negative regulator of differentiation into synthetic VSMCs. Knockdown of phospholipase A2, group 7 (Pla2g7) suppresses ROS formation in the MVSCs while enhancing SMC differentiation of MVSCs. These results suggest that cultured synthetic VSMCs can be derived from the SMC differentiation of MVSCs with ROS as a negative regulator.

  10. Sulforaphane inhibits PDGF-induced proliferation of rat aortic vascular smooth muscle cell by up-regulation of p53 leading to G1/S cell cycle arrest.

    Science.gov (United States)

    Yoo, Su-Hyang; Lim, Yong; Kim, Seung-Jung; Yoo, Kyu-Dong; Yoo, Hwan-Soo; Hong, Jin-Tae; Lee, Mi-Yea; Yun, Yeo-Pyo

    2013-01-01

    Vascular diseases such as atherosclerosis and restenosis artery angioplasty are associated with vascular smooth muscle cell (VSMC) proliferation and intimal thickening arterial walls. In the present study, we investigated the inhibitory effects of sulforaphane, an isothiocyanate produced in cruciferous vegetables, on VSMC proliferation and neointimal formation in a rat carotid artery injury model. Sulforaphane at the concentrations of 0.5, 1.0, and 2.0 μM significantly inhibited platelet-derived growth factor (PDGF)-BB-induced VSMC proliferation in a concentration-dependent manner, determined by cell count. The IC50 value of sulforaphane-inhibited VSMC proliferation was 0.8 μM. Sulforaphane increased the cyclin-dependent kinase inhibitor p21 and p53 levels, while it decreased CDK2 and cyclin E expression. The effects of sulforaphane on vascular thickening were determined 14 days after the injury to the rat carotid artery. The angiographic mean luminary diameters of the group treated with 2 and 4 μM sulforaphane were 0.25±0.1 and 0.09±0.1 mm², respectively, while the value of the control groups was 0.40±0.1 mm², indicating that sulforaphane may inhibit neointimal formation. The expression of PCNA, maker for cell cycle arrest, was decreased, while that of p53 and p21 was increased, which showed the same pattern as one in in-vitro study. These results suggest that sulforaphane-inhibited VSMC proliferation may occur through the G1/S cell cycle arrest by up-regulation of p53 signaling pathway, and then lead to the decreased neointimal hyperplasia thickening. Thus, sulforaphane may be a promising candidate for the therapy of atherosclerosis and post-angiography restenosis. © 2013.

  11. Vascular effects of 3-carbomethoxypyridine on rabbit aortic smooth ...

    African Journals Online (AJOL)

    Background: 3-Carbomethoxypyridine (3-CMP) is a methyl nicotinate that has been isolated and characterized from one of the alkaloidal fractions of Pyrenacantha staudtii. No literature is available on its vascular action. The goal of this study was to characterize the mechanism of action of 3-CMP on rabbit aortic smooth ...

  12. Vascular effects of 3-carbomethoxypyridine on rabbit aortic smooth ...

    African Journals Online (AJOL)

    ABSTRACT. Background: 3-Carbomethoxypyridine (3-CMP) is a methyl nicotinate that has been isolated and characterized from one of the alkaloidal fractions of Pyrenacantha staudtii. No literature is available on its vascular action. The goal of this study was to characterize the mechanism of action of 3-CMP on rabbit aortic ...

  13. Role of nitric oxide in hyporeactivity to noradrenaline of isolated aortic rings in portal hypertensive rats

    NARCIS (Netherlands)

    Michielsen, P. P.; Boeckxstaens, G. E.; Sys, S. U.; Herman, A. G.; Pelckmans, P. A.

    1995-01-01

    To test the hypothesis that induction of nitric oxide synthase causes systemic vascular hyporesponsiveness to vasopressors in portal hypertension, we performed in vitro experiments on isolated thoracic aortic rings from partial portal vein ligated or sham operated rats at 3 weeks postoperatively.

  14. In vitro assessment of mouse fetal abdominal aortic vascular function.

    Science.gov (United States)

    Renshall, Lewis J; Dilworth, Mark R; Greenwood, Susan L; Sibley, Colin P; Wareing, Mark

    2014-09-15

    Fetal growth restriction (FGR) affects 3-8% of human pregnancies. Mouse models have provided important etiological data on FGR; they permit the assessment of treatment strategies on the physiological function of both mother and her developing offspring. Our study aimed to 1) develop a method to assess vascular function in fetal mice and 2) as a proof of principle ascertain whether a high dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected fetal vascular reactivity. We developed a wire myography methodology for evaluation of fetal vascular function in vitro using the placenta-specific insulin-like growth factor II (Igf2) knockout mouse (P0; a model of FGR). Vascular function was determined in abdominal aortas isolated from P0 and wild-type (WT) fetuses at embryonic day (E) 18.5 of gestation. A subset of dams received SC 0.8 mg/ml via drinking water from E12.5; data were compared with water-only controls. Using wire myography, we found that fetal aortic rings exhibited significant agonist-induced contraction, and endothelium-dependent and endothelium-independent relaxation. Sex-specific alterations in reactivity were noted in both strains. Maternal treatment with SC significantly attenuated endothelium-dependent and endothelium-independent relaxation of fetal aortic rings. Mouse fetal abdominal aortas reproducibly respond to vasoactive agents. Study of these vessels in mouse genetic models of pregnancy complications may 1) help to delineate early signs of abnormal vascular reactivity and 2) inform whether treatments given to the mother during pregnancy may impact upon fetal vascular function. Copyright © 2014 the American Physiological Society.

  15. The effects of nicotine administration on the pathophysiology of rat aortic wall.

    Science.gov (United States)

    Kugo, H; Zaima, N; Tanaka, H; Urano, T; Unno, N; Moriyama, T

    2017-01-01

    Abdominal aortic aneurysm (AAA) is the progressive dilation of the abdominal aorta. Nicotine is reported to be associated with the development and rupture of AAA, but the pathological effects of nicotine on normal rat aorta have not been determined. We investigated pathological changes in the aortic wall of rats caused by the administration of nicotine. Nicotine administration weakened the vascular wall, increased gelatinolytic activity and promoted the destruction of elastin and collagen in the rat abdominal aorta. There were no differences in the areas positive for matrix metalloproteinase (MMP)-2 and MMP-9 between the control and nicotine treated groups. The areas positive for MMP-12 in the nicotine group were significantly greater than for the control group. Gelatinolytic activity in the aortic wall was increased significantly in the nicotine group. Our findings suggest that MMP-12 is sensitive to nicotine exposure in rats.

  16. Cordyceps sinensis extracts attenuate aortic transplant arteriosclerosis in rats.

    Science.gov (United States)

    Zhang, Yan; Yang, Mei; Gong, Shuwen; Yang, Yu; Chen, Bicheng; Cai, Yong; Zheng, Shaoling; Yang, Yirong; Xia, Peng

    2012-06-01

    Transplant arteriosclerosis is a hallmark of chronic rejection and is still the major limiting factor affecting the success of long-term organ transplants. Development of transplant arteriosclerosis is refractory to conventional immunosuppressive drugs, and adequate therapy is not yet available. The aim of this study was to determine the role of Cordyceps sinensis extracts in reducing the formation of transplant arteriosclerosis in a rat aortic transplant model. Lewis rat aortic allografts were transplanted into Brown-Norway recipient rats. Recipients received 0.5, 1, 2, and 5 mg/kg of Cordyceps sinensis extracts (or control saline) daily via intragastric injection for 60 d. Grafts were harvested 60 d post-transplantation and intimal thickness determined microscopically following hematoxylin and eosin (H and E) staining and abdominal aorta protein profiles determined by Western blot analysis. Cellular localization was assessed by histology and immunohistochemistry and the serum analyzed for tumor necrosis factor alpha (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) by enzyme-linked immunosorbent assay (ELISA). C. sinensis administration resulted in a significant reduction in neointimal formation (neointimal thickness 8.27 ± 1.95 μm [0.5 mg/kg], 3.69 ± 1.43 μm [1 mg/kg], 3.69 ± 1.43 μm [1 mg/kg], 3.69 ± 1.43 μm [1 mg/kg] versus 11.42 ± 2.67 μm [control]) and in the proliferative activity of vascular smooth muscle cells. In addition, localized expression of TNF-α and ICAM-1 in transplant aortas was characterized by immunohistochemistry and immunoblot analyses demonstrating that C. sinensis treatment significantly reduced TNF-α and ICAM-1 levels compared with levels observed in controls (P arteriosclerosis in a rat aortic transplant model. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Acid-base balance in uremic rats with vascular calcification.

    Science.gov (United States)

    Peralta-Ramírez, Alan; Raya, Ana Isabel; Pineda, Carmen; Rodríguez, Mariano; Aguilera-Tejero, Escolástico; López, Ignacio

    2014-01-01

    Vascular calcification (VC), a major complication in humans and animals with chronic kidney disease (CKD), is influenced by changes in acid-base balance. The purpose of this study was to describe the acid-base balance in uremic rats with VC and to correlate the parameters that define acid-base equilibrium with VC. Twenty-two rats with CKD induced by 5/6 nephrectomy (5/6 Nx) and 10 nonuremic control rats were studied. The 5/6 Nx rats showed extensive VC as evidenced by a high aortic calcium (9.2 ± 1.7 mg/g of tissue) and phosphorus (20.6 ± 4.9 mg/g of tissue) content. Uremic rats had an increased pH level (7.57 ± 0.03) as a consequence of both respiratory (PaCO2 = 28.4 ± 2.1 mm Hg) and, to a lesser degree, metabolic (base excess = 4.1 ± 1 mmol/l) derangements. A high positive correlation between both anion gap (AG) and strong ion difference (SID) with aortic calcium (AG: r = 0.604, p = 0.02; SID: r = 0.647, p = 0.01) and with aortic phosphorus (AG: r = 0.684, p = 0.007; SID: r = 0.785, p = 0.01) was detected. In an experimental model of uremic rats, VC showed high positive correlation with AG and SID.

  18. Abnormalities associated with progressive aortic vascular dysfunction in chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Omar Z Ameer

    2015-05-01

    Full Text Available Increased stiffness of large arteries in chronic kidney disease (CKD has significant clinical implications. This study investigates the temporal development of thoracic aortic dysfunction in a rodent model of CKD, the Lewis polycystic kidney (LPK rat. Animals aged 12 and 18 weeks were studied alongside age-matched Lewis controls (total n=94. LPK rodents had elevated systolic blood pressure, left ventricular hypertrophy and progressively higher plasma creatinine and urea. Relative to Lewis controls, LPK exhibited reduced maximum aortic vasoconstriction (Rmax to noradrenaline at 12 and 18 weeks, and to K+ (12 weeks. Sensitivity to noradrenaline was greater in 18-week-old LPK versus age matched Lewis (effective concentration 50%: 24×10-9 ± 78×10-10 vs. 19×10-8 ± 49×10-9, P<0.05. Endothelium-dependent (acetylcholine and -independent (sodium nitroprusside relaxation was diminished in LPK, declining with age (12 vs. 18 weeks Rmax: 80 ± 8% vs. 57 ± 9% and 92 ± 6% vs. 70 ± 9%, P<0.05, respectively in parallel with the decline in renal function. L-Arginine restored endothelial function in LPK, and L-NAME blunted acetylcholine relaxation in all groups. Impaired nitric oxide synthase (NOS activity was recovered with L-Arginine plus L-NAME in 12, but not 18-week-old LPK. Aortic calcification was increased in LPK rats, as was collagen I/III, fibronectin and NADPH-oxidase subunit p47 (phox mRNAs. Overall, our observations indicate that the vascular abnormalities associated with CKD are progressive in nature, being characterised by impaired vascular contraction and relaxation responses, concurrent with the development of endothelial dysfunction, which is likely driven by evolving deficits in NO signalling.

  19. Camptothecin inhibits platelet-derived growth factor-BB-induced proliferation of rat aortic vascular smooth muscle cells through inhibition of PI3K/Akt signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun-Seok [Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kang, Shin-il [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of); Yoo, Kyu-dong [Hazardous Substances Analysis Division, Gwangju Regional Food and Drug Administration, Gwangju (Korea, Republic of); Lee, Mi-Yea [Department of Nursing Kyungbok University, Pocheon (Korea, Republic of); Yoo, Hwan-Soo; Hong, Jin-Tae [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of); Shin, Hwa-Sup [Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kim, Bokyung [Department of Physiology, Konkuk Medical School, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Yun, Yeo-Pyo, E-mail: ypyun@chungbuk.ac.kr [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of)

    2013-04-15

    The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial wall is a major cause of vascular disorders such as atherosclerosis and restenosis after angioplasty. In this study, we investigated not only the inhibitory effects of camptothecin (CPT) on PDGF-BB-induced VSMC proliferation, but also its molecular mechanism of this inhibition. CPT significantly inhibited proliferation with IC50 value of 0.58 μM and the DNA synthesis of PDGF-BB-stimulated VSMCs in a dose-dependent manner (0.5–2 μM ) without any cytotoxicity. CPT induced the cell cycle arrest at G0/G1 phase. Also, CPT decreased the expressions of G0/G1-specific regulatory proteins including cyclin-dependent kinase (CDK)2, cyclin D1 and PCNA in PDGF-BB-stimulated VSMCs. Pre-incubation of VSMCs with CPT significantly inhibited PDGF-BB-induced Akt activation, whereas CPT did not affect PDGF-receptor beta phosphorylation, extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and phospholipase C (PLC)-γ1 phosphorylation in PDGF-BB signaling pathway. Our data showed that CPT pre-treatment inhibited VSMC proliferation, and that the inhibitory effect of CPT was enhanced by LY294002, a PI3K inhibitor, on PDGF-BB-induced VSMC proliferation. In addition, inhibiting the PI3K/Akt pathway by LY294002 significantly enhanced the suppression of PCNA expression and Akt activation by CPT. These results suggest that the anti-proliferative activity of CPT is mediated in part by downregulating the PI3K/Akt signaling pathway. - Highlights: ► CPT inhibits proliferation of PDGF-BB-induced VSMC without cytotoxicity. ► CPT arrests the cell cycle in G0/G1 phase by downregulation of cyclin D1 and CDK2. ► CPT significantly attenuates Akt phosphorylation in PDGF-BB signaling pathway. ► LY294002 enhanced the inhibitory effect of CPT on VSMC proliferation. ► Thus, CPT is mediated by downregulating the PI3K/Akt signaling pathway.

  20. Cyclic Stretch Alters Vascular Reactivity of Mouse Aortic Segments

    Directory of Open Access Journals (Sweden)

    Arthur Leloup

    2017-10-01

    Full Text Available Large, elastic arteries buffer the pressure wave originating in the left ventricle and are constantly exposed to higher amplitudes of cyclic stretch (10% than muscular arteries (2%. As a crucial factor for endothelial and smooth muscle cell function, cyclic stretch has, however, never been studied in ex vivo aortic segments of mice. To investigate the effects of cyclic stretch on vaso-reactivity of mouse aortic segments, we used the Rodent Oscillatory Tension Set-up to study Arterial Compliance (ROTSAC. The aortic segments were clamped at frequencies of 6–600 bpm between two variable preloads, thereby mimicking dilation as upon left ventricular systole and recoiling as during diastole. The preloads corresponding to different transmural pressures were chosen to correspond to a low, normal or high amplitude of cyclic stretch. At different time intervals, cyclic stretch was interrupted, the segments were afterloaded and isometric contractions by α1-adrenergic stimulation with 2 μM phenylephrine in the absence and presence of 300 μM L-NAME (eNOS inhibitor and/or 35 μM diltiazem (blocker of voltage-gated Ca2+ channels were measured. As compared with static or cyclic stretch at low amplitude (<10 mN or low frequency (0.1 Hz, cyclic stretch at physiological amplitude (>10 mN and frequency (1–10 Hz caused better ex vivo conservation of basal NO release with time after mounting. The relaxation of PE-precontracted segments by addition of ACh to stimulate NO release was unaffected by cyclic stretch. In the absence of basal NO release (hence, presence of L-NAME, physiological in comparison with aberrant cyclic stretch decreased the baseline tension, attenuated the phasic contraction by phenylephrine in the absence of extracellular Ca2+ and shifted the smaller tonic contraction more from a voltage-gated Ca2+ channel-mediated to a non-selective cation channel-mediated. Data highlight the need of sufficient mechanical activation of endothelial and

  1. Targeting vascular remodeling in abdominal aortic aneurysm : To identify novel treatment strategies and drug candidates

    OpenAIRE

    Vorkapić, Emina

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a degenerative weakening of the aortic wall, mainly affecting elderly men with a prevalence of 4.4-7.7 %. AAA is characterized by medial and adventitial inflammatory cell infiltration associated with vascular remodeling of the extracellular matrix proteins such as collagen and elastin and with phenotypic modulation and loss of vascular smooth muscle cells (VSMCs). Although much research has been performed, the precise cellular and molecular pathways behind t...

  2. Acid-Base Balance in Uremic Rats with Vascular Calcification

    Directory of Open Access Journals (Sweden)

    Alan Peralta-Ramírez

    2014-07-01

    Full Text Available Background/Aims: Vascular calcification (VC, a major complication in humans and animals with chronic kidney disease (CKD, is influenced by changes in acid-base balance. The purpose of this study was to describe the acid-base balance in uremic rats with VC and to correlate the parameters that define acid-base equilibrium with VC. Methods: Twenty-two rats with CKD induced by 5/6 nephrectomy (5/6 Nx and 10 nonuremic control rats were studied. Results: The 5/6 Nx rats showed extensive VC as evidenced by a high aortic calcium (9.2 ± 1.7 mg/g of tissue and phosphorus (20.6 ± 4.9 mg/g of tissue content. Uremic rats had an increased pH level (7.57 ± 0.03 as a consequence of both respiratory (PaCO2 = 28.4 ± 2.1 mm Hg and, to a lesser degree, metabolic (base excess = 4.1 ± 1 mmol/l derangements. A high positive correlation between both anion gap (AG and strong ion difference (SID with aortic calcium (AG: r = 0.604, p = 0.02; SID: r = 0.647, p = 0.01 and with aortic phosphorus (AG: r = 0.684, p = 0.007; SID: r = 0.785, p = 0.01 was detected. Conclusions: In an experimental model of uremic rats, VC showed high positive correlation with AG and SID.

  3. The effect of chronic nitric oxide inhibition on vascular reactivity and blood pressure in pregnant rats

    Directory of Open Access Journals (Sweden)

    Nilton Hideto Takiuti

    1999-09-01

    Full Text Available CONTEXT: The exact mechanism involved in changes in blood pressure and peripheral vascular resistance during pregnancy is unknown. OBJECTIVE:To evaluate the importance of endothelium-derivated relaxing factor (EDRF and its main component, nitric oxide, in blood pressure and vascular reactivity in pregnant rats. DESIGN: Clinical trial in experimentation animals. SETTING: University laboratory of Pharmacology. SAMPLE: Female Wistar rats with normal blood pressure, weight (152 to 227 grams and age (90 to 116 days. INTERVENTION: The rats were divided in to four groups: pregnant rats treated with L-NAME (13 rats; pregnant control rats (8 rats; virgin rats treated with L-NAME (10 rats; virgin control rats (12 rats. The vascular preparations and caudal blood pressure were obtained at the end of pregnancy, or after the administration of L-NAME in virgin rats. MAIN MEASUREMENTS: The caudal blood pressure and the vascular response to acetylcholine in pre-contracted aortic rings, both with and without endothelium, and the effect of nitric oxide inhibition, Nw-L-nitro-arginine methyl-ester (L-NAME, in pregnant and virgin rats. The L-NAME was administered in the drinking water over a 10-day period. RESULTS: The blood pressure decreased in pregnancy. Aortic rings of pregnant rats were more sensitive to acetylcholine than those of virgin rats. After L-NAME treatment, the blood pressure increased and relaxation was blocked in both groups. The fetal-placental unit weight of the L-NAME group was lower than that of the control group. CONCLUSION: Acetylcholine-induced vasorelaxation sensitivity was greater in pregnant rats and that blood pressure increased after L-NAME administration while the acetylcholine-induced vasorelaxation response was blocked.

  4. Flaxseed oil increases aortic reactivity to phenylephrine through reactive oxygen species and the cyclooxygenase-2 pathway in rats.

    Science.gov (United States)

    Nunes, Dieli Oliveira; Almenara, Camila Cruz Pereira; Broseghini-Filho, Gilson Brás; Silva, Marito Afonso Sousa Costa; Stefanon, Ivanita; Vassallo, Dalton V; Padilha, Alessandra S

    2014-07-03

    Flaxseed oil has the highest concentration of omega-3 α-linolenic acid, which has been associated with cardiovascular benefit. However, the mechanism underlying the vascular effects induced through flaxseed oil is not well known. Thus, in the present study, we investigated the effects of flaxseed oil on vascular function in isolated rat aortic rings. Wistar rats were treated daily with flaxseed oil or a control (mineral oil) intramuscular (i.m.) for fifteen days. Isolated aortic segments were used to evaluate cyclooxygenase-2 (COX-2) protein expression, superoxide anion levels and vascular reactivity experiments. Flaxseed oil treatment increased the vasoconstrictor response of aortic rings to phenylephrine. Endothelium removal increased the response to phenylephrine in aortic segments isolated from both groups, but the effect was smaller in the treated group. L-NAME incubation similarly increased the phenylephrine response in segments from both groups. The TXA2 synthase inhibitor furegrelate, the selective COX-2 inhibitor NS 398, the TP receptor antagonist SQ 29.548, the reactive oxygen species (ROS) scavenger apocynin, the superoxide anion scavengers tiron and the phospholipase A2 inhibitor dexamethasone partially reversed the flaxseed oil-induced increase in reactivity to phenylephrine. These findings suggest that flaxseed oil treatment increased vascular reactivity to phenylephrine through an increase in ROS production and COX-2-derived TXA2 production. The results obtained in the present study provide new insight into the effects of flaxseed oil treatment (i.m.) on vascular function.

  5. Vascular calcification and aortic fibrosis: a bifunctional role for osteopontin in diabetic arteriosclerosis.

    Science.gov (United States)

    Shao, Jian-Su; Sierra, Oscar L; Cohen, Richard; Mecham, Robert P; Kovacs, Attila; Wang, James; Distelhorst, Kathryn; Behrmann, Abraham; Halstead, Linda R; Towler, Dwight A

    2011-08-01

    Calcification and fibrosis reduce vascular compliance in arteriosclerosis. To better understand the role of osteopontin (OPN), a multifunctional protein upregulated in diabetic arteries, we evaluated contributions of OPN in male low-density lipoprotein receptor (LDLR)-/- mice fed a high-fat diet. OPN had no impact on high-fat diet-induced hyperglycemia, dyslipidemia, or body composition. However, OPN-/-;LDLR-/- mice exhibited an altered time-course of aortic calcium accrual-reduced during initiation but increased with progression-versus OPN+/+;LDLR-/- controls. Collagen accumulation, chondroid metaplasia, and mural thickness were increased in aortas of OPN-/-;LDLR-/- mice. Aortic compliance was concomitantly reduced. Vascular reexpression of OPN (SM22-OPN transgene) reduced aortic Col2A1 and medial chondroid metaplasia but did not affect atherosclerotic calcification, Col1A1 expression, collagen accumulation, or arterial stiffness. Dosing with the proinflammatory OPN fragment SVVYGLR upregulated aortic Wnt and osteogenic gene expression, increased aortic β-catenin, and restored early-phase aortic calcification in OPN-/-;LDLR-/- mice. OPN exerts stage-specific roles in arteriosclerosis in LDLR-/- mice. Actions phenocopied by the OPN metabolite SVVYGLR promote osteogenic calcification processes with disease initiation. OPN limits vascular chondroid metaplasia, endochondral mineralization, and collagen accumulation with progression. Complete deficiency yields a net increase in arteriosclerotic disease, reducing aortic compliance and conduit vessel function in LDLR-/- mice.

  6. MDCT assessment of tracheomalacia in symptomatic infants with mediastinal aortic vascular anomalies: preliminary technical experience

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Edward Y. [Children' s Hospital Boston and Harvard Medical School, Departments of Radiology and Medicine, Pulmonary Division, Boston, MA (United States); Mason, Keira P. [Children' s Hospital Boston and Harvard Medical School, Department of Anesthesiology, Boston, MA (United States); Zurakowski, David [Children' s Hospital Boston and Harvard Medical School, Department of Orthopedic Surgery, Boston, MA (United States); Waltz, David A. [Children' s Hospital Boston and Harvard Medical School, Department of Medicine, Division of Respiratory Diseases, Boston, MA (United States); Ralph, Amy; Riaz, Farhana [Children' s Hospital Boston and Harvard Medical School, Department of Radiology, Boston, MA (United States); Boiselle, Phillip M. [Harvard Medical School, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA (United States)

    2008-01-15

    Mediastinal aortic vascular anomalies are relatively common causes of extrinsic central airway narrowing in infants with respiratory symptoms. Surgical correction of mediastinal aortic vascular anomalies alone might not adequately treat airway symptoms if extrinsic narrowing is accompanied by intrinsic tracheomalacia (TM), a condition that escapes detection on routine end-inspiratory imaging. Paired inspiratory-expiratory multidetector CT (MDCT) has the potential to facilitate early diagnosis and timely management of TM in symptomatic infants with mediastinal aortic vascular anomalies. To assess the technical feasibility of paired inspiratory-expiratory MDCT for evaluating TM among symptomatic infants with mediastinal aortic vascular anomalies. The study group consisted of five consecutive symptomatic infants (four male, one female; mean age 4.1 months, age range 2 weeks to 6 months) with mediastinal aortic vascular anomalies who were referred for paired inspiratory-expiratory MDCT during a 22-month period. CT angiography was concurrently performed during the end-inspiration phase of the study. Two pediatric radiologists in consensus reviewed all CT images in a randomized and blinded fashion. The end-inspiration and end-expiration CT images were reviewed for the presence and severity of tracheal narrowing. TM was defined as {>=}50% reduction in tracheal cross-sectional luminal area between end-inspiration and end-expiration. The presence of TM was compared to the bronchoscopy results when available (n = 4). Paired inspiratory-expiratory MDCT was technically successful in all five patients. Mediastinal aortic vascular anomalies included a right aortic arch with an aberrant left subclavian artery (n = 2), innominate artery compression (n = 2), and a left aortic arch with an aberrant right subclavian artery (n = 1). Three (60%) of the five patients demonstrated focal TM at the level of mediastinal aortic vascular anomalies. The CT results were concordant with the

  7. Goldenhar syndrome with right circumflex aortic arch, severe coarctation and vascular ring in a twin pregnancy

    Directory of Open Access Journals (Sweden)

    Elaheh Malakan Rad

    2014-01-01

    Full Text Available Goldenhar syndrome (GS or oculo-auriculo-vertebral dysplasia (OAVD, involves a wide variety of organ systems. Cardiovascular anomalies are among the frequent malformations. The purpose of this report is to introduce a male case of a dizygotic twin pregnancy with GS and right circumflex aortic arch (RCAA, severe coarctation, hypoplastic aortic arch, aberrant right subclavian artery, vascular ring, bilateral renal artery stenosis, and mild Dandy-Walker syndrome. The embryology of RCAA and coarctation is revisited.

  8. Goldenhar syndrome with right circumflex aortic arch, severe coarctation and vascular ring in a twin pregnancy.

    Science.gov (United States)

    Rad, Elaheh Malakan

    2014-09-01

    Goldenhar syndrome (GS) or oculo-auriculo-vertebral dysplasia (OAVD), involves a wide variety of organ systems. Cardiovascular anomalies are among the frequent malformations. The purpose of this report is to introduce a male case of a dizygotic twin pregnancy with GS and right circumflex aortic arch (RCAA), severe coarctation, hypoplastic aortic arch, aberrant right subclavian artery, vascular ring, bilateral renal artery stenosis, and mild Dandy-Walker syndrome. The embryology of RCAA and coarctation is revisited.

  9. Frequency and Effect of Access-Related Vascular Injury and Subsequent Vascular Intervention After Transcatheter Aortic Valve Replacement

    DEFF Research Database (Denmark)

    Dencker, Ditte; Taudorf, Mikkel; Luk, N H Vincent

    2016-01-01

    Vascular access and closure remain a challenge in transcatheter aortic valve replacement (TAVR). This single-center study aimed to report the incidence, predictive factors, and clinical outcomes of access-related vascular injury and subsequent vascular intervention. During a 30-month period, 365...... patients underwent TAVR and 333 patients (94%) were treated by true percutaneous transfemoral approach. Of this latter group, 83 patients (25%) had an access-related vascular injury that was managed by the use of a covered self-expanding stent (n = 49), balloon angioplasty (n = 33), or by surgical...... for access-related vascular intervention. In addition, a high sheath/common femoral artery ratio as measured on preoperative CTA was associated with a higher rate of post-TAVR vascular intervention. The radiation dose, iodine contrast volume, transfusion need, length of hospitalization, and 30-day mortality...

  10. Effects of Crataegus microphylla on vascular dysfunction in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Topal, Gökçe; Koç, Ebru; Karaca, Cetin; Altuğ, Tuncay; Ergin, Bülent; Demirci, Cihan; Melikoğlu, Gülay; Meriçli, Ali H; Kucur, Mine; Ozdemir, Osman; Uydeş Doğan, B Sönmez

    2013-03-01

    Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease. In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla (CM) extract in diabetic rats induced with streptozotocin (STZ, intraperitoneal, 65 mg/kg) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase (iNOS), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action. Starting at 4 weeks of diabetes, CM extract (100 mg/kg) was administrated to diabetic rats for 4 weeks. In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), total nitrite-nitrate, and malondialdehite levels were increased in diabetic rats compared with controls. Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of diabetic rats with N-[3(aminomethyl) benzyl]-acetamidine, dihydrochloride (10(-5)  M), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity. These results suggest that chronic in vivo treatment of CM preserves endothelium-dependent relaxation and vascular contraction in STZ-induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF-α and IL-6 and by preventing lipid peroxidation. Copyright © 2012 John Wiley & Sons, Ltd.

  11. Vascular Adaptations to Transverse Aortic Banding in Mice

    National Research Council Canada - National Science Library

    Hartley, Craig

    2001-01-01

    .... Results showed that mean aortic, mitral, and carotid velocities were similar in sham and banded mice, but peak RCA/LCA velocities were much higher in banded mice and were highly correlated to HW...

  12. Losartan Inhibits Vascular Calcification by Suppressing the BMP2 and Runx2 Expression in Rats In Vivo.

    Science.gov (United States)

    Li, Mincai; Wu, Panfeng; Shao, Juan; Ke, Zhiqiang; Li, Dan; Wu, Jiliang

    2016-04-01

    The blockade of renin-angiotensin II system has been shown to reduce morbidity and mortality in hypertension, atherosclerosis, diabetes and chronic kidney disease. Since vascular calcification (VC) is commonly found in these diseases, the aim of this study was to examine whether or not losartan, a widely used angiotensin II receptor blockers, inhibits VC in rats in vivo. A rat model of VC was generated by treating rats with a combination of warfarin and vitamin K1. Two weeks after the treatments, the rats were treated with vehicle or without losartan (100 ng/kg/day) for 2 weeks. At the end of the experiments, aortic arteries were isolated for the examination of calcification morphology, mRNA and protein expression of BMP2 and Runx2, and osteoblast differentiation. Warfarin and vitamin K instigated vascular remodeling with calcified plaques in the aortic arteries in rats. Losartan significantly attenuated warfarin- and vitamin K-induced vascular injury and calcification. Consistently, losartan suppressed the levels of mRNA and protein expression of BMP2 and Runx2, two key factors for VC. Further, vascular calcified lesion areas expressed angiotensin II 1 receptor (AT1R). Finally, losartan treatment significantly inhibited apoptosis in vascular smooth muscle cell (VSMC) in rat arteries. We conclude that losartan suppresses VC by lowering the expression of AT1R, Runx2 and BMP2, and by inhibiting the apoptosis of VSMC in rat aortic arteries.

  13. Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings

    Energy Technology Data Exchange (ETDEWEB)

    López-Canales, J.S. [Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City (Mexico); Department of Cellular Biology, National Institute of Perinatology, Mexico City (Mexico); Lozano-Cuenca, J.; Muãoz-Islas, E.; Aguilar-Carrasco, J.C. [Department of Cellular Biology, National Institute of Perinatology, Mexico City (Mexico); López-Canales, O.A.; López-Mayorga, R.M.; Castillo-Henkel, E.F.; Valencia-Hernández, I.; Castillo-Henkel, C. [Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City (Mexico)

    2015-03-27

    Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca{sup 2+}-activated K{sup +} channels were involved in this effect.

  14. Mineralocorticoids participate in the reduced vascular reactivity of pregnant rats.

    Science.gov (United States)

    Provencher, M; Houde, V; Brochu, M; St-Louis, J

    2012-03-01

    The renin-angiotensin-aldosterone (RAA) system is markedly activated in pregnancy. We evaluated if mineralocorticoid receptors (MR), a major component of the RAA system, are involved in the reduced vascular reactivity associated with pregnancy. Canrenoate (MR antagonist; 20 mg·kg(-1)·day(-1)) was administered to nonpregnant (NP) rats for 7 days and to pregnant rats from day 15 to 22 of gestation. These were killed on day 17, 19, or 22 of gestation and, for NP rats, after 7 days treatment. Constrictor responses to phenylephrine (PhE) and KCl were measured in endothelium-denuded thoracic aortic rings under the influence of modulators of potassium (activators) and calcium (blocker) channels. Responses to the constrictors were blunted from days 17 to 22 of gestation. Although canrenoate increased responses to PhE and KCl, it did not reverse their blunted responses in gestation. NS-1619 and cromakalim (respectively, high-conductance calcium-activated potassium channels and ATP-sensitive potassium channel activators) diminished responses to both PhE and KCl. Inhibition by NS-1619 on responses to both agonists was decreased under canrenoate treatment in NP, but the reduced influence of NS-1619 during gestation was reversed by the mineralocorticoid antagonist. Cromakalim reduced the response to PhE significantly in the pregnant groups; this effect was enhanced by canrenoate. Finally, nifedipine (calcium channel blocker) markedly reduced KCl responses but to a lesser extent at the end of pregnancy, an inhibiting effect that was increased with canrenoate treatment. These data demonstrate that treating rats with a MR antagonist increased vascular reactivity but that it differentially affected potassium and calcium channel activity in aortas of NP and pregnant animals. This suggests that aldosterone is one of the components involved in vascular adaptations to pregnancy.

  15. Frequency and Effect of Access-Related Vascular Injury and Subsequent Vascular Intervention After Transcatheter Aortic Valve Replacement.

    Science.gov (United States)

    Dencker, Ditte; Taudorf, Mikkel; Luk, N H Vincent; Nielsen, Michael B; Kofoed, Klaus F; Schroeder, Torben V; Søndergaard, Lars; Lönn, Lars; De Backer, Ole

    2016-10-15

    Vascular access and closure remain a challenge in transcatheter aortic valve replacement (TAVR). This single-center study aimed to report the incidence, predictive factors, and clinical outcomes of access-related vascular injury and subsequent vascular intervention. During a 30-month period, 365 patients underwent TAVR and 333 patients (94%) were treated by true percutaneous transfemoral approach. Of this latter group, 83 patients (25%) had an access-related vascular injury that was managed by the use of a covered self-expanding stent (n = 49), balloon angioplasty (n = 33), or by surgical intervention (n = 1). In 16 patients (5%), the vascular injury was classified as a major vascular complication. Absence of a preprocedural computed tomography angiography (CTA) of the iliofemoral arteries (OR 2.04, p = 0.007) and female gender (OR 2.18, p = 0.004) were independent predictors of the need for access-related vascular intervention. In addition, a high sheath/common femoral artery ratio as measured on preoperative CTA was associated with a higher rate of post-TAVR vascular intervention. The radiation dose, iodine contrast volume, transfusion need, length of hospitalization, and 30-day mortality were not significantly different between patients with versus without access-related vascular intervention. In conclusion, access-related vascular intervention in patients who underwent transfemoral-TAVR is not uncommon. Female gender and a high sheath/common femoral artery ratio are risk factors for access-related vascular injury, whereas preprocedural planning with CTA of the access vessels may reduce the risk of vascular injury. Importantly, most access-related vascular injuries may be treated by percutaneous techniques with similar clinical outcomes to patients without vascular injuries. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Vascular disease patient information page: Abdominal aortic aneurysm (AAA).

    Science.gov (United States)

    Moennich, Laurie Ann; Mastracci, Tara M

    2014-10-01

    Abdominal aortic aneurysm is a silent but often fatal disease. AAA is most common in older people, with both modifiable (such as smoking) and hereditary (family history of AAA) risk factors influencing disease development. Screening for AAA can aid in the early diagnosis and treatment of the disease, reducing complications and death amongst those affected. Advancements in screening techniques, surgical innovations, and graft development strive to further improve patient outcomes and disease management.

  17. Controlled release of ascorbic acid from gelatin hydrogel attenuates abdominal aortic aneurysm formation in rat experimental abdominal aortic aneurysm model.

    Science.gov (United States)

    Tanaka, Akiko; Hasegawa, Tomomi; Morimoto, Keisuke; Bao, Wulan; Yu, Jie; Okita, Yutaka; Tabata, Yasuhiko; Okada, Kenji

    2014-09-01

    Abdominal aortic aneurysms (AAAs) are associated with oxidative stress and inflammatory response. We investigated the hypothesis that the known antioxidant ascorbic acid, which can also promote elastin and collagen production by smooth muscle cells, would prevent AAA formation in a rat model. An intraluminal elastase and extraluminal calcium chloride-induced rat AAA model was used, and the animals were divided into three groups: control (group C, n = 18), the aorta wrapped with a saline-impregnated gelatin hydrogel sheet (group G, n = 18), and the aorta wrapped with a gelatin hydrogel sheet incorporating ascorbic acid (group A, n = 18). Wrapping of the sheet was completed at the end of treatment for AAA creation. The aortic dilatation ratio was measured, and aortic tissues were further examined for oxidative stress and oxidative DNA damage using biochemical and histologic techniques. Aortic dilatation at both 4 and 8 weeks was inhibited in group A (dilatation ratio [%] at 4 weeks: 186.2 ± 21.8 in group C, 152.3 ± 10.2 in group G, 126.8 ± 11.6 in group A; P < .0001; dilatation ratio [%] at 8 weeks: 219.3 ± 37.5 in group C, 194.0 ± 11.6 in group G, 145.7 ± 8.3 in group A; P = .0002). Elastin and collagen content were significantly preserved in group A (elastin, P = .0015; collagen, P < .0001). The messenger RNA expressions of matrix metalloproteinase (MMP)-9, monocyte chemotactic protein-1, interleukin-1β, and tissue necrosis factor-α (P = .0024, P < .0001, P < .0001, and P < .0001, respectively) were downregulated in group A (P = .0024), whereas tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were both upregulated in group A (TIMP-1, P = .0014; TIMP-2, P < .0001). Gelatin zymography showed activities of pro-MMP-2, MMP-2, and MMP-9 were significantly suppressed in group C (P < .0001 for each). Reactive oxygen species expression and 8-hydroxydeoxyguanosine and cluster of differentiation 68 staining were significantly suppressed in group A (reactive

  18. Endovascular repair of abdominal aortic aneurysms: vascular anatomy, device selection, procedure, and procedure-specific complications.

    Science.gov (United States)

    Bryce, Yolanda; Rogoff, Philip; Romanelli, Donald; Reichle, Ralph

    2015-01-01

    Abdominal aortic aneurysm (AAA) is abnormal dilatation of the aorta, carrying a substantial risk of rupture and thereby marked risk of death. Open repair of AAA involves lengthy surgery time, anesthesia, and substantial recovery time. Endovascular aneurysm repair (EVAR) provides a safer option for patients with advanced age and pulmonary, cardiac, and renal dysfunction. Successful endovascular repair of AAA depends on correct selection of patients (on the basis of their vascular anatomy), choice of the correct endoprosthesis, and familiarity with the technique and procedure-specific complications. The type of aneurysm is defined by its location with respect to the renal arteries, whether it is a true or false aneurysm, and whether the common iliac arteries are involved. Vascular anatomy can be divided more technically into aortic neck, aortic aneurysm, pelvic perfusion, and iliac morphology, with grades of difficulty with respect to EVAR, aortic neck morphology being the most common factor to affect EVAR appropriateness. When choosing among the devices available on the market, one must consider the patient's vascular anatomy and choose between devices that provide suprarenal fixation versus those that provide infrarenal fixation. A successful technique can be divided into preprocedural imaging, ancillary procedures before AAA stent-graft placement, the procedure itself, postprocedural medical therapy, and postprocedural imaging surveillance. Imaging surveillance is important in assessing complications such as limb thrombosis, endoleaks, graft migration, enlargement of the aneurysm sac, and rupture. Last, one must consider the issue of radiation safety with regard to EVAR. (©)RSNA, 2015.

  19. In vitro assessment of mouse fetal abdominal aortic vascular function

    OpenAIRE

    Renshall, Lewis J.; Dilworth, Mark R.; Greenwood, Susan L.; Sibley, Colin P.; Wareing, Mark

    2014-01-01

    Fetal growth restriction (FGR) affects 3?8% of human pregnancies. Mouse models have provided important etiological data on FGR; they permit the assessment of treatment strategies on the physiological function of both mother and her developing offspring. Our study aimed to 1) develop a method to assess vascular function in fetal mice and 2) as a proof of principle ascertain whether a high dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected fetal vascular reactivit...

  20. Impact of post-dialysis calcium level on ex vivo rat aortic wall calcification.

    Science.gov (United States)

    Azpiazu, Daniel; González-Parra, Emilio; Ortiz, Alberto; Egido, Jesús; Villa-Bellosta, Ricardo

    2017-01-01

    Vascular calcification is a frequent complication in chronic haemodialysis patients and is associated with adverse outcomes. Serum calcium and phosphate levels and imbalances in calcification regulators are thought to contribute to the process. In this regard, the dialysate calcium concentration is a modifiable tool for modulating the risk of vascular calcification. We explored pre- and post-dialysis phosphate and calcium concentrations in stable chronic haemodialysis patients treated by dialysis with the KDIGO-suggested 1.5 mmol/L calcium dialysate to investigate the effects on ex vivo calcification of rat aortic rings. At the end of haemodialysis, mean serum calcium levels were increased in 88% of paired pre-/post-dialysis samples, while mean serum phosphate and parathyroid hormone levels were decreased. Rat aortic ring cultures grown at the same calcium and phosphate concentrations revealed that pre- and post-dialysis resulted in a similar degree of calcification. By contrast, haemodialysis with unchanged serum calcium resulted in a 5-fold reduction in calcium deposition. Dialysis with the widely prescribed 1.5 mmol/L calcium dose results in persistent high serum calcification potential in a sizable proportion of patients, driven by increased post-dialysis calcium concentration. This could potentially be mitigated by individualising dialysate calcium dosage based on pre-dialysis serum calcium levels.

  1. Etelcalcetide, A Novel Calcimimetic, Prevents Vascular Calcification in A Rat Model of Renal Insufficiency with Secondary Hyperparathyroidism.

    Science.gov (United States)

    Yu, Longchuan; Tomlinson, James E; Alexander, Shawn T; Hensley, Kelly; Han, Chun-Ya; Dwyer, Denise; Stolina, Marina; Dean, Charles; Goodman, William G; Richards, William G; Li, Xiaodong

    2017-12-01

    Etelcalcetide, a novel peptide agonist of the calcium-sensing receptor, prevents vascular calcification in a rat model of renal insufficiency with secondary hyperparathyroidism. Vascular calcification occurs frequently in patients with chronic kidney disease (CKD) and is a consequence of impaired mineral homeostasis and secondary hyperparathyroidism (SHPT). Etelcalcetide substantially lowers parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) levels in SHPT patients on hemodialysis. This study compared the effects of etelcalcetide and paricalcitol on vascular calcification in rats with adenine-induced CKD and SHPT. Uremia and SHPT were induced in male Wistar rats fed a diet supplemented with 0.75% adenine for 4 weeks. Rats were injected with vehicle, etelcalcetide, or paricalcitol for 4 weeks from the beginning of adenine diet. Rats fed an adenine-free diet were included as nonuremic controls. Similar reductions in plasma PTH and parathyroid chief cell proliferation were observed in both etelcalcetide- and paricalcitol-treated rats. Serum calcium and phosphorus were significantly lower in etelcalcetide-treated uremic rats and was unchanged in paricalcitol-treated rats. Both serum FGF23 and aortic calcium content were significantly lower in etelcalcetide-treated uremic rats compared with either vehicle- or paricalcitol-treated uremic rats. The degree of aortic calcium content for etelcalcetide-treated rats was similar to that in nonuremic controls and corroborated findings of lack of histologic aortic mineralization in those groups. In conclusion, etelcalcetide and paricalcitol similarly attenuated progression of SHPT in an adenine rat model of CKD. However, etelcalcetide differentially prevented vascular calcification, at least in part, due to reductions in serum FGF23, calcium, and phosphorus levels.

  2. Brief report: biomarkers of aortic vascular prosthetic graft infection in a porcine model with Staphylococcus aureus

    DEFF Research Database (Denmark)

    Langerhuus, S. N.; Tønnesen, E. K.; Jensen, K. H.

    2010-01-01

    Aortic vascular prosthetic graft infection (AVPGI) with Staphylococcus aureus is a feared post-operative complication. This study was conducted to evaluate the clinical signs and potential biomarkers of infection in a porcine AVPGI model. The biomarkers evaluated were: C-reactive protein (CRP......), fibrinogen, white blood cells (WBC), major histocompatibility complex II (MHC II) density, lymphocyte CD4:CD8 ratio and tumour necrosis factor-alpha (TNF-α) in vitro responsiveness. Sixteen pigs were included in the study, and randomly assigned into four groups (n = 4): “SHAM” pigs had their infra-renal...... aorta exposed by laparotomy; “CLEAN” pigs had an aortic graft inserted; “LOW” and “HIGH” pigs had an aortic graft inserted and, subsequently, S. aureus were inoculated on the graft material (5 × 104 colony-forming units [CFU] and 1 × 106 CFU, respectively). Biomarkers were evaluated prior to surgery...

  3. Vascular effect of lead on rabbit aortic smooth muscle | Inneh ...

    African Journals Online (AJOL)

    Several reports have demonstrated a positive link between lead exposure and hypertension (Navas et al., 2007 and Heydari et al., 2006). It has also been suggested that alterations in vascular reactivity is one of several mechanisms by which lead induces hypertension (Webb et al., 1981). There are conflicting reports ...

  4. Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

    Science.gov (United States)

    Parastatidis, Ioannis; Weiss, Daiana; Joseph, Giji; Taylor, W Robert

    2013-01-01

    Objective Elevated levels of oxidative stress have been reported in abdominal aortic aneurysms (AAA), but which reactive oxygen species (ROS) promotes the development of AAA remains unclear. Here we investigate the effect of the hydrogen peroxide (H2O2) degrading enzyme catalase on the formation of AAA. Approach and Results AAA were induced with the application of calcium chloride (CaCl2) on mouse infrarenal aortas. The administration of PEG-catalase, but not saline, attenuated the loss of tunica media and protected against AAA formation (0.91±0.1 mm vs. 0.76±0.09 mm). Similarly, in a transgenic mouse model, catalase over-expression in the vascular smooth muscle cells (VSMC) preserved the thickness of tunica media and inhibited aortic dilatation by 50% (0.85±0.14 mm vs. 0.57±0.08 mm). Further studies showed that injury with CaCl2 decreased catalase expression and activity in the aortic wall. Pharmacologic administration or genetic over-expression of catalase restored catalase activity and subsequently decreased matrix metalloproteinase activity. In addition, a profound reduction in inflammatory markers and VSMC apoptosis was evident in aortas of catalase over-expressing mice. Interestingly, as opposed to infusion of PEG-catalase, chronic over-expression of catalase in VSMC did not alter the total aortic H2O2 levels. Conclusions The data suggest that a reduction in aortic wall catalase activity can predispose to AAA formation. Restoration of catalase activity in the vascular wall enhances aortic VSMC survival and prevents AAA formation primarily through modulation of matrix metalloproteinase activity. PMID:23950141

  5. Ghrelin improves vascular autophagy in rats with vascular calcification.

    Science.gov (United States)

    Xu, Mingming; Liu, Lin; Song, Chenfang; Chen, Wei; Gui, Shuyan

    2017-06-15

    This study aimed to investigate whether ghrelin ameliorated vascular calcification (VC) through improving autophagy. VC model was induced by nicotine plus vitamin D 3 in rats and β-glycerophosphate in vascular smooth muscle cell (VSMC). Calcium deposition was detected by von Kossa staining or alizarin red S staining. ALP activity was also detected. Western blot was used to assess the protein expression. Ghrelin treatment attenuated the elevation of calcium deposition and ALP activity in VC model both in vivo and in vitro. Interesting, the protein levels of autophagy markers, LC3 and beclin1 were significantly upregulated by ghrelin in VC model. An autophagy inhibitor, 3-methyladenine blocks the ameliorative effect of ghrelin on VC. Furthermore, protein expressions of phosphate-AMPK were increased by ghrelin treatment both in calcified aorta and VSMC. The effect of ghrelin on autophagy induction and VC attenuation was prevented by AMPK inhibitor, compound C. Our results suggested that ghrelin improved autophagy through AMPK activation, which was resulted in VC amelioration. These data maybe throw light on prevention and therapy of VC. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Differential effects of vitamin D receptor activators on aortic calcification and pulse wave velocity in uraemic rats.

    Science.gov (United States)

    Noonan, William; Koch, Kristin; Nakane, Masaki; Ma, Junli; Dixon, Doug; Bolin, Antoinette; Reinhart, Glenn

    2008-12-01

    Vascular calcification is associated with an increase in cardiovascular mortality in stage 5 chronic kidney disease. To determine if vitamin D receptor activators (VDRAs) have differential effects in the pathogenesis of aortic calcification, we assessed the effects of paricalcitol and doxercalciferol in vivo using 5/6 nephrectomized (NX) rats. To quantify the functional consequences of vascular calcification, pulse wave velocity (PWV), an aortic compliance index, was measured. NX rats were fed a diet containing 0.9% phosphorous and 0.6% calcium 4 weeks prior to and throughout the study. On Day 0, rats received vehicle or VDRA (0.083, 0.167 and 0.333 microg/kg, i.p.) three times per week for 6 weeks. At Day 0 and Weeks 2 and 6, blood was drawn and PWV was measured by Doppler ultrasound. VDRAs (0.167 and 0.333 microg/kg) consistently lowered PTH at Weeks 2 and 6. All doses of paricalcitol increased serum calcium at Week 6 but not at Week 2, while the two higher doses of doxercalciferol increased serum calcium at both Weeks 2 and 6. Treatment with paricalcitol (0.333 microg/kg) increased serum phosphorus at Weeks 2 and 6; these changes were not different from those observed in 5/6 NX rats. All doses of doxercalciferol increased serum phosphorus at Week 6. Paricalcitol had no effect on Ca x P; however, the two highest doses of doxercalciferol increased Ca x P at Weeks 2 and 6 above that observed in the 5/6 NX vehicle-treated group. There were no differences in aortic calcium and phosphorus contents at the end of 6 weeks among SHAM-, 5/6 NX- and paricalcitol-treated rats. However, treatment with the two higher doses of doxercalciferol caused a significant elevation in aortic calcium and phosphorus contents. Measurements of PWV demonstrated differential effects of VDRAs on vascular compliance. Paricalcitol produced no effects on PWV, while the two highest doses of doxercalciferol increased PWV at Week 6. In uraemic rats with established secondary hyperparathyroidism, we

  7. Surgical Management of Percutaneous Transfemoral Access to Minimize Vascular Complications Related to Transcatheter Aortic Valve' Implantation.

    Science.gov (United States)

    Lareyre, Fabien; Raffort, Juliette; Dommerc, Carine; Habib, Yacoub; Bourlon, François; Mialhe, Claude

    2018-02-01

    Transcatheter aortic valve implantation (TAVI) is associated with substantial rates of vascular complications. The aim of our study is to describe the surgical management of percutaneous transfemoral access by a vascular surgeon and to report the 30-day postoperative vascular complications and mortality. Perioperative procedures to manage the femoral access site were recorded retrospectively from 220 consecutive patients who underwent TAVI. Postoperative vascular complications related to the main access were categorized according to the Valve Academic Research Consortium 2 classification. Perioperative procedures related to vascular access were performed for 56 (25.4%) patients: 6 patients required open surgical repair, 48 patients underwent endovascular stenting, and 2 patients had both procedures. The all-cause mortality was 3.6%, but no death related to a vascular complication was reported during the 30-day postoperative follow-up period. Ten (4.5%) patients developed postoperative hematomas; 2 (0.9%) of them were retroperitoneal and led to major bleeding requiring an unplanned surgical intervention. Our study underlines the utility of a multidisciplinary approach to manage the percutaneous access in TAVI for managing postoperative vascular complications.

  8. Data for the Oxford Abdominal Aortic Aneurysm Study international survey of vascular surgery professionals.

    Science.gov (United States)

    Lee, Regent; Jones, Amy; Woodgate, Felicity; Killough, Nicholas; Bellamkonda, Kirthi; Williams, Matthew; Hurst, Katherine; Fulford-Smith, Lucy; Cassimjee, Ismail; Handa, Ashok

    2017-10-01

    As part of the Oxford Abdominal Aortic Aneurysm (OxAAA) Study, we conducted an international survey of vascular surgery professionals. One aspect of the survey is as published in the International Journal of Cardiology: "International Opinion on Priorities in Research for Small Abdominal Aortic Aneurysms and the Potential Path for Research to Impact Clinical Management". This Data-in-Brief article contains a detailed method for the conduct of this survey and additional original data. In this survey, we also provided vascular surgery colleagues with contemporary epidemiologic and surgical outcome data. This was followed by a hypothetical scenario whereby a patient had just been diagnosed with a small (40 mm) AAA and a novel biomarker predicted it to be fast growing in the coming years. We assessed the vascular professionals' perception of the patient's preference for management in this scenario, and their willingness to refer patients for a surgical trial that investigates the outcome of early versus late surgery in this setting. The survey then asked the vascular professionals to assume the role of the patient, and provided their own preferences in such a scenario.

  9. Single-walled carbon nanotubes (SWCNTs) induce vasodilation in isolated rat aortic rings.

    Science.gov (United States)

    Gutiérrez-Hernández, J M; Ramirez-Lee, M A; Rosas-Hernandez, H; Salazar-García, S; Maldonado-Ortega, D A; González, F J; Gonzalez, C

    2015-06-01

    Single-walled carbon nanotubes (SWCNTs) are used in biological systems with impact in biomedicine in order to improve diagnostics and treatment of diseases. However, their effects upon the vascular system, are not fully understood. Endothelium and smooth muscle cells (SMC) communicate through release of vasoactive factors as nitric oxide (NO) to maintain vascular tone. The aim of this study was to evaluate the effect of SWCNTs on vascular tone using isolated rat aortic rings, which were exposed to SWCNTs (0.1, 1 and 10 μg/mL) in presence and absence of endothelium. SWCNTs induced vasodilation in both conditions, indicating that this effect was independent on endothelium; moreover that vasodilation was NO-independent, since its blockage with L-NAME did not modify the observed effect. Together, these results indicate that SWCNTs induce vasodilation in the macrovasculature, may be through a direct interaction with SMC rather than endothelium independent of NO production. Further investigation is required to fully understand the mechanisms of action and mediators involved in the signaling pathway induced by SWCNTs on the vascular system. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. A role for soluble ST2 in vascular remodeling associated with obesity in rats.

    Directory of Open Access Journals (Sweden)

    Ernesto Martínez-Martínez

    Full Text Available BACKGROUND: The function of the Interleukin-33 (IL-33/ST2 system has been mainly investigated on immunological aspects, but recent data suggest that this pathway plays also an important role in cardiovascular system and adipose tissue. Whereas IL-33 has been demonstrated to exert anti-inflammatory and protective effects, circulating soluble ST2 (sST2 has emerged as a prognostic biomarker in patients with myocardial infarction and heart failure. Furthermore, sST2 is increased in severe obesity, although its role in the pathogenesis of vascular remodeling associated with obesity is still not well defined. METHODOLOGY/PRINCIPAL FINDINGS: Male Wistar rats fed standard diet (Control or high fat diet (HFD for 6 weeks. Aortic tunica media from diet-induced obese animals showed hypertrophy and fibrosis. The IL-33/ST2 system was spontaneously expressed in the aorta from Wistar rats. Administration of HFD in animals did not modify IL-33 expression at the transcriptional level. By contrast, HFD group showed an increase in aortic soluble sST2 and a decrease in the transmembrane isoform (ST2L levels, resulting in decreased protective pathway activity. Aortic sST2 mRNA levels were associated with parameters showing vascular hypertrophy and fibrosis. In vitro experiments showed that primary cultured vascular smooth muscle cells (VSMCs spontaneously expressed the IL-33/ST2 system. VSMCs stimulated with sST2 showed an increase in collagen type I, fibronectin and profibrotic factors. CONCLUSIONS: This is the first study demonstrating a deleterious role for sST2 in the vascular remodeling associated with obesity. In addition, we demonstrated that sST2 may act not only as a decoy receptor by binding IL-33 and preventing ST2L, but also modulating ECM remodeling and turnover. Thus, sST2 could be a new therapeutic target to reduce vascular remodeling in the context of obesity.

  11. Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Penghao [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Xie, Qihai [Department of Cardiology, Shanghai Jiading District Central Hospital, Shanghai (China); Wei, Tong [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Chen, Yichen [Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Chen, Hong, E-mail: hchen100@shsmu.edu.cn [Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Shen, Weili, E-mail: wlshen@sibs.ac.cn [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

    2015-12-04

    Objective: Obesity-induced vascular dysfunction is related to chronic low-grade systemic inflammation. Recent studies indicate that NLRP3, a multiprotein complex formed by NOD-like receptor (NLR) family members, is a key component mediating internal sterile inflammation, but the role in obesity-related vascular dysfunction is largely unknown. In the present study, we investigate whether NLRP3 activation is involved in vascular inflammation in obese Otsuka Long-Evans Tokushima Fatty rats (OLETF). Methods and results: Male OLETF with their control Long-Evans Tokushima Otsuka rats (LETO) were studied at 3 and 12 months of age. Aortic relaxation in response to acetylcholine decreased gradually with age in both strains, with early and persistent endothelium dysfunction in obese OLETF compared with age-matched LETO controls. These changes are associated with parallel changes of aortic endothelial nitric oxide synthase (eNOS) content, macrophage accumulation and intimal thickening. NLRP3 increased in OLETF rats compared to LETO. Consistent with inflammasome activation, the conversion of procaspase-1 to cleaved and activated forms as well as IL-1β markedly increased in OLETF rats. Additionally, we observed increased expression of dynamin-related protein-1 (Drp1) and decreased fusion-relative protein optic atropy-1(OPA1). Altered mitochondrial dynamics was associated with elevated oxidative stress level in OLETF aortas. Conclusions: These results demonstrate that obesity seems to accelerate endothelial dysfunction in OLETFs via the activation of NLRP3 and mitochondrial dysfunction. - Highlights: • NLRP3 is involved in obesity-induced vascular dysfunction. • Impaired mitochondrial dynamics may have been linked to mitochondrial defect and inflammasome activation. • Obesity seems to accelerate vascular dysfunction via NLRP3 activation and mitochondrial dysfunction.

  12. Chronic lead exposure decreases the vascular reactivity of rat aortas: the role of hydrogen peroxide.

    Directory of Open Access Journals (Sweden)

    Karolini Zuqui Nunes

    Full Text Available We investigated whether exposure to small concentrations of lead alters blood pressure and vascular reactivity. Male Wistar rats were sorted randomly into the following two groups: control (Ct and treatment with 100 ppm of lead (Pb, which was added to drinking water, for 30 days. Systolic blood pressure (BP was measured weekly. Following treatment, aortic ring vascular reactivity was assessed. Tissue samples were properly stored for further biochemical investigation. The lead concentration in the blood reached approximately 8 μg/dL. Treatment increased blood pressure and decreased the contractile responses of the aortic rings to phenylephrine (1 nM-100 mM. Following N-nitro-L arginine methyl ester (L-NAME administration, contractile responses increased in both groups but did not differ significantly between them. Lead effects on Rmax were decreased compared to control subjects following superoxide dismutase (SOD administration. Catalase, diethyldithiocarbamic acid (DETCA, and apocynin increased the vasoconstrictor response induced by phenylephrine in the aortas of lead-treated rats but did not increase the vasoconstrictor response in the aortas of untreated rats. Tetraethylammonium (TEA potentiated the vasoconstrictor response induced by phenylephrine in aortic segments in both groups, but these effects were greater in lead-treated rats. The co-incubation of TEA and catalase abolished the vasodilatory effect noted in the lead group. The present study is the first to demonstrate that blood lead concentrations well below the values established by international legislation increased blood pressure and decreased phenylephrine-induced vascular reactivity. The latter effect was associated with oxidative stress, specifically oxidative stress induced via increases in hydrogen peroxide levels and the subsequent effects of hydrogen peroxide on potassium channels.

  13. VASCULAR INFLAMMATION AND ABNORMAL AORTIC HISTOMORPHOMETRY IN PATIENTS FOLLOWING PULSATILE AND CONTINUOUS FLOW LEFT VENTRICULAR ASSIST DEVICE PLACEMENT

    Science.gov (United States)

    Lee, Mike; Akashi, Hirokazu; Kato, Tomoko S.; Takayama, Hiroo; Wu, Christina; Xu, Katherine; Collado, Elias; Weber, Matthew P.; Kennel, Peter J.; Brunjes, Danielle L; Ji, Ruiping; Naka, Yoshifumi; George, Isaac; Mancini, Donna; Farr, Maryjane; Schulze, P. Christian

    2017-01-01

    Objective Left ventricular assist devices are increasingly used in patients with advanced heart failure as both destination therapy and bridge-to-transplantation. We aimed to analyze histomorphometric, structural and inflammatory changes following pulsatile and continuous flow left ventricular assist device placement. Method Clinical and echocardiographic data were collected from medical records. Aortic wall diameter, cellularity and inflammation were assessed by immunohistochemistry on aortic tissue collected at left ventricular assist device placement and at explantation during heart transplantation. Expression of adhesion molecules was quantified by western blot. Results Decellularization of the aortic tunica media was observed in patients receiving continuous flow support. Both device types showed an increased inflammatory response following left ventricular assist device placement with variable T cell and macrophage accumulations and increased expression of vascular E-selectin, ICAM and VCAM in the aortic wall. Conclusion Left ventricular assist device implantation is associated with distinct vascular derangements with development of vascular inflammation. These changes are pronounced in patients on continuous flow left ventricular assist and associated with aortic media decellularization. These findings help to explain the progressive aortic root dilation and vascular dysfunction in patients following continuous flow device placement. PMID:26899764

  14. Smooth muscle LDL receptor-related protein-1 deletion induces aortic insufficiency and promotes vascular cardiomyopathy in mice.

    Directory of Open Access Journals (Sweden)

    Joshua E Basford

    Full Text Available Valvular disease is common in patients with Marfan syndrome and can lead to cardiomyopathy. However, some patients develop cardiomyopathy in the absence of hemodynamically significant valve dysfunction, suggesting alternative mechanisms of disease progression. Disruption of LDL receptor-related protein-1 (Lrp1 in smooth muscle cells has been shown to cause vascular pathologies similar to Marfan syndrome, with activation of smooth muscle cells, vascular dysfunction and aortic aneurysms. This study used echocardiography and blood pressure monitoring in mouse models to determine whether inactivation of Lrp1 in vascular smooth muscle leads to cardiomyopathy, and if so, whether the mechanism is a consequence of valvular disease. Hemodynamic changes during treatment with captopril were also assessed. Dilation of aortic roots was observed in young Lrp1-knockout mice and progressed as they aged, whereas no significant aortic dilation was detected in wild type littermates. Diastolic blood pressure was lower and pulse pressure higher in Lrp1-knockout mice, which was normalized by treatment with captopril. Aortic dilation was followed by development of aortic insufficiency and subsequent dilated cardiomyopathy due to valvular disease. Thus, smooth muscle cell Lrp1 deficiency results in aortic dilation and insufficiency that causes secondary cardiomyopathy that can be improved by captopril. These findings provide novel insights into mechanisms of cardiomyopathy associated with vascular activation and offer a new model of valvular cardiomyopathy.

  15. Mechanisms of improved aortic stiffness by arotinolol in spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Wugang Zhou

    Full Text Available OBJECTIVES: This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR. METHODS: The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO was measured in human aortic endothelial cells (HAECs by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d⁻¹, arotinolol (30 mg·kg-1·d⁻¹ for 8 weeks. Central arterial pressure (CAP and pulse wave velocity (PWV were evaluated via catheter pressure transducers. Collagen was assessed by immunohistochemistry and biochemistry assay, while endothelial nitric oxide synthase (eNOS and eNOS phosphorylation (p-eNOS of HAECs or aortas were analyzed by western blotting. RESULTS: Arotinolol relaxed vascular rings and the relaxations were attenuated by Nω-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor and the absence of endothelium. Furthermore, arotinolol-induced relaxations were attenuated by 4-aminopyridine (4-AP, Kv channels blocker. Arotinolol produced more nitric oxide compared to metoprolol and increased the expression of p-eNOS in HAECs. These results indicated that arotinolol-induced vasodilation involves endothelium-derived NO and Kv channels. The treatement with arotinolol in 8 weeks, but not metoprolol, markedly decreased CAP and PWV. Biochemistry assay and immunohistochemistry showed that aortic collagen depositions in the arotinolol groups were reduced compared with SHRs with metoprolol. Moreover, eNOS phosphorylation was significantly increased in aortinolol-treated SHR compared with SHRs with metoprolol. CONCLUSIONS: Arotinolol improves arterial stiffness in SHR, which involved in increasing NO and decreasing collagen contents in large arteries.

  16. Mechanisms of improved aortic stiffness by arotinolol in spontaneously hypertensive rats.

    Science.gov (United States)

    Zhou, Wugang; Hong, Mona; Zhang, Ke; Chen, Dongrui; Han, Weiqing; Shen, Weili; Zhu, Dingliang; Gao, Pingjin

    2014-01-01

    This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR). The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO) was measured in human aortic endothelial cells (HAECs) by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d⁻¹), arotinolol (30 mg·kg-1·d⁻¹) for 8 weeks. Central arterial pressure (CAP) and pulse wave velocity (PWV) were evaluated via catheter pressure transducers. Collagen was assessed by immunohistochemistry and biochemistry assay, while endothelial nitric oxide synthase (eNOS) and eNOS phosphorylation (p-eNOS) of HAECs or aortas were analyzed by western blotting. Arotinolol relaxed vascular rings and the relaxations were attenuated by Nω-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and the absence of endothelium. Furthermore, arotinolol-induced relaxations were attenuated by 4-aminopyridine (4-AP, Kv channels blocker). Arotinolol produced more nitric oxide compared to metoprolol and increased the expression of p-eNOS in HAECs. These results indicated that arotinolol-induced vasodilation involves endothelium-derived NO and Kv channels. The treatement with arotinolol in 8 weeks, but not metoprolol, markedly decreased CAP and PWV. Biochemistry assay and immunohistochemistry showed that aortic collagen depositions in the arotinolol groups were reduced compared with SHRs with metoprolol. Moreover, eNOS phosphorylation was significantly increased in aortinolol-treated SHR compared with SHRs with metoprolol. Arotinolol improves arterial stiffness in SHR, which involved in increasing NO and decreasing collagen contents in large arteries.

  17. Successful renal transplantation decreases aortic stiffness and increases vascular reactivity in dialysis patients.

    Science.gov (United States)

    Covic, A; Goldsmith, D J A; Gusbeth-Tatomir, P; Buhaescu, I; Covic, M

    2003-12-15

    Patients with end-stage renal disease on dialysis have among the highest cardiovascular event rates documented. Abnormal nitric oxide (NO)-dependent endothelial reactivity and increased arterial stiffness are commonly described in hemodialysis (HD) patients. Measures of aortic stiffness--aortic pulse wave velocity (PWV) and augmentation index (AGI)--have been shown to be powerful predictors of survival on hemodialysis. It is not known how these parameters interfere with successful renal transplantation. PWV and aortic AGI (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse wave height) were determined from contour analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCor device in 41 HD patients (20 men; age, 41.8 years) and in a control group of 20 patients with essential hypertension (HTA) (10 men; age, 43.6 years). Twenty of the HD patients (10 men; age, 39.7 years) received live-related renal transplants (RTx) and were restudied (3 months after RTx, normal serum creatinine). NO-dependent and NO-independent vascular reactivity were assessed by changes in AGI after challenges with inhaled salbutamol (SAL) and sublingual nitroglycerin (NTG), respectively. AGI values were significantly lower in RTx patients compared with subjects on hemodialysis (15.9 +/- 13.9% vs. 27.9 +/- 11.9%, Pdialysis to 15.9 +/- 7.0% 3 months after transplantation (Pdialysis patients (7.19 +/- 1.88 m/sec) were significantly higher than those measured in essential HTA patients (6.34 +/- 1.32 m/sec, Pdialysis) values (P<0.05 for comparison) but similar to the control group of essential HTA patients. Renal transplantation is associated with marked improvements in vascular structure and function to a profile comparable to essential HTA patients.

  18. Berberine Attenuates Vascular Remodeling and Inflammation in a Rat Model of Metabolic Syndrome.

    Science.gov (United States)

    Li, Xiao-Xing; Li, Chuan-Bao; Xiao, Jie; Gao, Hai-Qing; Wang, He-Wen; Zhang, Xin-Yu; Zhang, Cheng; Ji, Xiao-Ping

    2015-01-01

    Berberine is a natural product that shows benefits for metabolic syndrome (MS). However, the effects of berberine on the improvement of vascular inflammation and remodeling in MS remain unclear. This study aimed to investigate whether berberine could prevent vascular remodeling and inflammation in the MS condition. A rat model of MS was established, and MS rats were divided into two groups: MS group without berberine treatment, and MSB group with berberine treatment (each group n-10). Ten normal Wistar rats were used as controls (NC group). Vascular damage was examined by transmission electron microscopy and pathological staining. Compared to the NC group, the secretion of inflammatory factors was increased and the aortic wall thicker in the MS group. The MSB group exhibited decreased secretion of inflammatory factors and improved vascular remodeling, compared to the MS group. In addition, the levels of p38 mitogen-activated protein kinase (p38 MAPK), activating transcription factor 2 (ATF-2) and matrix metalloproteinase 2 (MMP-2) were significantly decreased in the MSB group compared to the MS group. In conclusion, our data show that berberine improves vascular inflammation and remodeling in the MS condition, and this is correlated with the ability of berberine to inhibit p38 MAPK activation, ATF-2 phosphorylation, and MMP-2 expression.

  19. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    Directory of Open Access Journals (Sweden)

    J. Lozano-Cuenca

    Full Text Available Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10–9–10–5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10–7.5–10–5 M. The present outcome was not modified by 10–6 M atropine (an antagonist of muscarinic acetylcholine receptors, 3.1×10–7 M glibenclamide (an ATP-sensitive K+ channel blocker, 10–3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker, 10–5 M indomethacin (a prostaglandin synthesis inhibitor, 10–5 M clotrimazole (a cytochrome P450 inhibitor or 10–5 M cycloheximide (a general protein synthesis inhibitor. Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05 by 10–5 M L-NAME (a direct inhibitor of nitric oxide synthase, 10–7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase, 10–6 M KT 5823 (an inhibitor of protein kinase G, 10–2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker and 10–7 M apamin plus 10–7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively, and was blocked by 8×10–2 M potassium (a high concentration and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

  20. Prevalence of blood type A and risk of vascular complications following transcatheter aortic valve implantation.

    Science.gov (United States)

    Rofe, M-T; Shacham, Y; Steinvi, A; Barak, L; Hareuveni, M; Banai, S; Keren, G; Finkelstein, A; Shmilovich, H

    2016-05-01

    To assess the prevalence of blood type A among patients referred for transcatheter aortic valve implantation (TAVI) and whether it is related to vascular complications. Vascular complications following TAVI are associated with adverse outcomes. Various blood types, particularly type A, have been shown to be more prevalent in cardiovascular diseases and to be related to prognosis. The prevalence of various blood types in a cohort of 491 consecutive patients who underwent TAVI was compared with a control group of 6500 consecutive hospitalised patients. The prevalence and predictors of vascular complications and bleeding events were evaluated in the blood type A group and were compared with non-type A patients. The mean age of TAVI patients was 83 ± 6 years, and 40 % were males. Patients were divided into two groups: blood type A (n = 220) and non-type A (n = 271). Type A was significantly more prevalent in the TAVI group than in the control group (45 vs. 38 %, p = 0.023). Compared with the non-type A group, patients with blood type A had more major and fatal bleeding (14.5 vs. 8.1 %, p = 0.027) and more vascular complications (any vascular complication: 24.5 vs. 15.9 % p = 0.016; major vascular complications: 12.3 vs. 7 % p = 0.047). In a multivariable analysis, blood type A emerged as a significant and independent predictor for vascular complications and bleeding events. Blood type A is significantly more prevalent in TAVI patients than in the general population and is related to higher rates of vascular and bleeding complications.

  1. Time course of the hemodynamic responses to aortic depressor nerve stimulation in conscious spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Durand, M.T.; Mota, A.L. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Barale, A.R. [Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG (Brazil); Castania, J.A.; Fazan, R. Jr.; Salgado, H.C. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-16

    The time to reach the maximum response of arterial pressure, heart rate and vascular resistance (hindquarter and mesenteric) was measured in conscious male spontaneously hypertensive (SHR) and normotensive control rats (NCR; Wistar; 18-22 weeks) subjected to electrical stimulation of the aortic depressor nerve (ADN). The parameters of stimulation were 1 mA intensity and 2 ms pulse length applied for 5 s, using frequencies of 10, 30, and 90 Hz. The time to reach the hemodynamic responses at different frequencies of ADN stimulation was similar for SHR (N = 15) and NCR (N = 14); hypotension = NCR (4194 ± 336 to 3695 ± 463 ms) vs SHR (3475 ± 354 to 4494 ± 300 ms); bradycardia = NCR (1618 ± 152 to 1358 ± 185 ms) vs SHR (1911 ± 323 to 1852 ± 431 ms), and the fall in hindquarter vascular resistance = NCR (6054 ± 486 to 6550 ± 847 ms) vs SHR (4849 ± 918 to 4926 ± 646 ms); mesenteric = NCR (5574 ± 790 to 5752 ± 539 ms) vs SHR (5638 ± 648 to 6777 ± 624 ms). In addition, ADN stimulation produced baroreflex responses characterized by a faster cardiac effect followed by a vascular effect, which together contributed to the decrease in arterial pressure. Therefore, the results indicate that there is no alteration in the conduction of the electrical impulse after the site of baroreceptor mechanical transduction in the baroreflex pathway (central and/or efferent) in conscious SHR compared to NCR.

  2. Diffusion of Alexa Fluor 488-conjugated dendrimers in rat aortic tissue.

    Science.gov (United States)

    Cho, Brenda S; Roelofs, Karen J; Majoros, Istvan J; Baker, James R; Stanley, James C; Henke, Peter K; Upchurch, Gilbert R

    2006-11-01

    In this study, the distribution of labeled dendrimers in native and aneurysmal rat aortic tissue was examined. Adult male rats underwent infrarenal aorta perfusion with generation 5 (G5) acetylated Alexa Fluor 488-conjugated dendrimers for varying lengths of time. In a second set of experiments, rats underwent aortic elastase perfusion followed by aortic dendrimer perfusion 7 days later. Aortic diameters were measured prior to and postelastase perfusion, and again on the day of harvest. Aortas were harvested 0, 12, or 24 h postperfusion, fixed, and mounted. Native aortas were harvested and viewed as negative controls. Aortic cross-sections were viewed and imaged using confocal microscopy. Dendrimers were quantified (counts/high-powered field). Results were evaluated by repeated measures ANOVA and Student's t-test. We found that in native aortas, dendrimers penetrated the aortic wall in all groups. For all perfusion times, fewer dendrimers were present as time between dendrimer perfusion and aortic harvest increased. Longer perfusion times resulted in increased diffusion of dendrimers throughout the aortic wall. By 24 h, the majority of the dendrimers were through the wall. Dendrimers in aneurysmal aortas, on day 0 postdendrimer perfusion, diffused farther into the aortic wall than controls. In conclusion, this study documents labeled dendrimers delivered intra-arterially to native rat aortas in vivo, and the temporal diffusion of these molecules within the aortic wall. Increasing perfusion time and length of time prior to harvest resulted in continued dendrimer diffusion into the aortic wall. These preliminary data provide a novel mechanism whereby local inhibitory therapy may be delivered locally to aortic tissue.

  3. Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive mice developing aortic aneurysm.

    Science.gov (United States)

    Waeckel, Ludovic; Badier-Commander, Cécile; Damery, Thibaut; Köhler, Ralf; Sansilvestri-Morel, Patricia; Simonet, Serge; Vayssettes-Courchay, Christine; Wulff, Heike; Félétou, Michel

    2015-09-01

    Angiotensin-II and oxidative stress are involved in the genesis of aortic aneurysms, a phenomenon exacerbated by endothelial nitric oxide synthase (eNOS) deletion or uncoupling. The purpose of this work was to study the endothelial function in wild-type C57BL/6 (BL) and transgenic mice expressing the h-angiotensinogen and h-renin genes (AR) subjected to either a control, or a high-salt diet plus a treatment with a NO-synthase inhibitor, N-ω-nitro-L-arginine-methyl-ester (L-NAME; BLSL and ARSL). BLSL showed a moderate increase in blood pressure, while ARSL became severely hypertensive. Seventy-five percent of ARSL developed aortic aneurysms, characterized by major histo-morphological changes and associated with an increase in NADP(H) oxidase-2 (NOX2) expression. Contractile responses (KCl, norepinephrine, U-46619) were similar in the four groups of mice, and relaxations were not affected in BLSL and AR. However, in ARSL, endothelium-dependent relaxations (acetylcholine, UK-14304) were significantly reduced, and this dysfunction was similar in aortae without or with aneurysms. The endothelial impairment was unaffected by catalase, superoxide-dismutase mimetic, radical scavengers, cyclooxygenase inhibition, or TP-receptor blockade and could not be attributed to sGC oxidation. Thus, ARSL is a severe hypertension model developing aortic aneurysm. A vascular dysfunction, involving both endothelial (reduced role of NO) and smooth muscle cells, precedes aneurysms formation and, paradoxically, does not appear to involve oxidative stress.

  4. 41. The myocardial protective effect of dexmedetomidine in high risk patients undergoing aortic vascular surgery

    Directory of Open Access Journals (Sweden)

    R. Soliman

    2016-07-01

    Full Text Available Dexmedetomidine provides perioperative cardiac protection in high risk patients assessment the effect of dexmedetomidine in high risk patients undergoing aortic vascular surgery. Arandomized study included 150 patients classified into two groups(n = 75. Group D: The patients received a loading dose of 1 μg/kg dexmedetomidine over 15 min before induction and maintained as an infusion of 0.3 μg/kg/hr to the end of the procedure. Group C: The patients received an equal volume of normalsaline. The dexmedetomidine decreased heart rate and minimized the changes in blood pressure compared to control group (p < 0.05. Also, it decreased the incidence of myocardial is chemia reflected by troponin I level and ECG changes(p < 0.05. Dexmedetomidine decreased the requirement for nitroglycerine and norepinephrine compared to control group (p < 0.05. The incidence of hypotension and bradycardia were significantly higher with dexmedetomidine (p < 0.05.The dexmedetomidine is safe and effective in patients undergoing aortic vascular surgery. It decreases the changes in heart rate and blood pressure during the procedures. It provide scardiac protection in high risk patients reflected by decreasing the incidence of myocardial ischemia and serum level of troponin. The main side effects of dexmedetomidine were hypotension and bradycardia.

  5. Aortic histomine syntesis in experimental neurogenic hypertension.

    Science.gov (United States)

    Bolitho, G A; Hollis, T M

    1975-04-01

    Aortic histamine synthesis of normotensive rats has been compared to that of rats rendered hypertensive via production carotid sinus ischemia and to animals additionally subjected to bilateral adrenalectomy. Results indicate that the aortic histamine-forming capacities (HFC's) of rats sacrificed 24 hr after surgical treatment were elevated 83% and 103% for hypertensive rats and those additionally subjected to adrenalectomy, respectively. At an 8-day postoperative interval, the respective aortic HFC's were elevated over control by 33% and 45%, although at this time interval animals were not considered hypertensive. This study thus offers suggestive evidence that hypertension causes increased vascular permeability by increasing the histamine-forming capacity of the vessel wall.

  6. Bioengineering functional human aortic vascular smooth-muscle strips in vitro.

    Science.gov (United States)

    Hecker, Louise; Khait, Luda; Welsh, Michael J; Birla, Ravi

    2008-07-01

    The contraction and relaxation of VSM (vascular smooth muscle) are responsible for the maintenance of vascular tone, which is a major determinant of blood pressure. However, the molecular events leading to the contraction and relaxation of VSM are poorly understood. The development of three-dimensional bioengineered tissues provides an opportunity to investigate the molecular events controlling vascular tone in vitro. In the present study we used fibrin-gel casting to bioengineer functional VSM strips from primary human aortic VSM cells. Our bioengineered VSM strips are functionally similar to VSM in vivo and remained viable in culture for up to 5 weeks. VSM strips demonstrate spontaneous basal tone and can generate an active force (contraction) of up to 85.2 microN on stimulation with phenylephrine. Bioengineered VSM strips exhibited Ca(2+)-dependent contraction and calcium-independent relaxation. The development of functional bioengineered VSM tissue provides a new in vitro model system that can be used to investigate the molecular events controlling vascular tone.

  7. Effect of Curcumin on Angiogenesis in Aortic Ring Model of the Wistar Rat

    Directory of Open Access Journals (Sweden)

    J Baharara

    2014-08-01

    Conclusion: The results proposed that the Curcumin had dose-dependent inhibitory effects on angiogenesis in rat aortic ring Therefore, it can be introduced as an appropriate candidate in order to study angiogenesis and related diseases.

  8. Incidence and predictors of vascular access site complications following transfemoral transcatheter aortic valve implantation.

    Science.gov (United States)

    Fonseca, Paulo; Almeida, João; Bettencourt, Nuno; Ferreira, Nuno; Carvalho, Mónica; Ferreira, Wilson; Caeiro, Daniel; Gonçalves, Helena; Ribeiro, José; Rodrigues, Alberto; Braga, Pedro; Gama, Vasco

    2017-10-01

    Vascular access site complications in transfemoral (TF) transcatheter aortic valve implantation (TAVI) are associated with increased morbidity and mortality; however, their incidence and predictors are conflicting between studies. This study sought to assess the incidence and predictors of vascular access site complications in patients undergoing TF TAVI. A total of 140 patients undergoing TF TAVI were included in the study. Minimum iliofemoral diameter and iliofemoral calcium score (CS) were estimated from contrast-enhanced multidetector computed tomography imaging, using different thresholds according to aortic luminal attenuation. To assess the impact of the learning effect, the first 50% of TF TAVI procedures were compared to the remainder. Fifty-one patients presented access site complications (7.1% major, 29.3% minor), most of which were local bleeding or hematoma (11.4%), pseudoaneurysm (7.9%) or closure device failure (5.0%). In a multivariate logistic regression analysis that included sheath-to-iliofemoral artery ratio (SIFAR) (the ratio between the sheath outer diameter and minimum iliofemoral diameter), iliofemoral CS and center experience, SIFAR was the sole independent predictor of access site complications (hazard ratio 14.5, confidence interval [CI] 95% 1.75-120.12, p=0.013). The SIFAR threshold with the highest sum of sensitivity (71.4%) and specificity (53.4%) for access site complications was 0.92 (area under the curve 0.66, 95% CI 0.56-0.75, p=0.002). Vascular access site complications are frequent in patients undergoing TF TAVI. SIFAR was the only independent predictor of access site complications and therefore should be systematically assessed during pre-procedural imaging study. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. The impact of pressure overload on coronary vascular changes following myocardial infarction in rats

    Science.gov (United States)

    Chen, Jiqiu; Petrov, Artiom; Yaniz-Galende, Elisa; Liang, Lifan; de Haas, Hans J.; Narula, Jagat

    2013-01-01

    This study investigates the impact of pressure overload on vascular changes after myocardial infarction (MI) in rats. To evaluate the effect of pressure overload, MI was induced in three groups: 1) left coronary artery ligation for 1 mo (MI-1m), 2) ischemia 30 min/reperfusion for 1 mo (I/R-1m), and 3) ischemia-reperfusion (I/R) was performed after pressure overload induced by aortic banding for 2 mo; 1 mo post-I/R, aortic constriction was released (Ab+I/R+DeAb). Heart function was assessed by echocardiography and in vivo hemodynamics. Resin casting and three-dimensional imaging with microcomputed tomography were used to characterize changes in coronary vasculature. TTC (triphenyltetrazohum chloride) staining and Masson's Trichrome were conducted in parallel experiments. In normal rats, MI induced by I/R and permanent occlusion was transmural or subendocardial. Occluded arterial branches vanished in MI-1m rats. A short residual tail was retained, distal to the occluded site in the ischemic area in I/R-1m hearts. Vascular pathological changes in transmural MI mostly occurred in ischemic areas and remote vasculature remained normal. In pressure overloaded rats, I/R injury induced a sub-MI in which ischemia was transmural, but myocardium in the involved area had survived. The ischemic arterial branches were preserved even though the capillaries were significantly diminished and the pathological changes were extended to remote areas, characterized by fibrosis, atrial thrombus, and pulmonary edema in the Ab+I/R+DeAb group. Pressure overload could increase vascular tolerance to I/R injury, but also trigger severe global ventricular fibrosis and results in atrial thrombus and pulmonary edema. PMID:23275620

  10. Antioxidative properties of acetylsalicylic Acid on vascular tissues from normotensive and spontaneously hypertensive rats.

    Science.gov (United States)

    Wu, Rong; Lamontagne, Daniel; de Champlain, Jacques

    2002-01-22

    The mechanisms of the beneficial cardiovascular effects of acetylsalicylic acid (ASA, aspirin) therapy are not completely understood. Oxidative stress and inflammation play important roles in the development of cardiovascular diseases. In this study, we tested the hypothesis that ASA treatment could reduce superoxide anion (O(2)(-)) generation in aortic ring and in cultured aortic smooth muscle cells (SMCs) from normotensive (WKY) and hypertensive (SHRs) rats by means of the Lucigenin-enhanced chemiluminescence method. Although ASA did not show any short-term effect in vitro and in vivo, long-term oral treatment (100 mg/kg/day, 12 days) significantly reduced the basal O(2)(-) production by 27% and 45% in aorta of normotensive and hypertensive rats, respectively, in association with a reduction of the NAD(P)H oxidase activity in both groups. These effects were dose-dependent from 10 to 100 mg/kg/day. Similar effects were observed in SMCs following long-term incubation (48 hours) with ASA. ASA treatment also completely inhibited the angiotensin II-induced hypertension and O(2)(-) production. Moreover, ASA treatment significantly improved the impaired aortic relaxation response to acetylcholine and markedly attenuated the age-dependent development of hypertension in SHRs. Long-term ASA treatment in vivo markedly reduced vascular O(2)(-) production through lowering the NAD(P)H oxidase activity in both normotensive and hypertensive rats. These antioxidative properties of ASA are likely involved in the restoration of aortic vasorelaxation, in the attenuation of the development of hypertension in young SHRs, and in the prevention of hypertension following long-term angiotensin II infusion.

  11. Synchrotron radiation X-ray fluorescence microscopy reveals a spatial association of copper on elastic laminae in rat aortic media.

    Science.gov (United States)

    Qin, Zhenyu; Toursarkissian, Boulos; Lai, Barry

    2011-08-01

    Copper, an essential trace metal in humans, plays an important role in elastic formation. However, little is known about the spatial association between copper, elastin, and elastin producing cells. The aorta is the largest artery; the aortic media is primarily composed of the elastic lamellae and vascular smooth muscle cells, which makes it a good model to address this issue. Synchrotron radiation X-ray fluorescence microscopy (SRXRF) is a new generation technique to investigate the spatial topography of trace metals in biological samples. Recently, we utilized this technique to determine the topography of copper as well as other trace elements in aortic media of Sprague Dawley rats. A standard rat diet was used to feed Sprague Dawley rats, which contains the normal dietary requirements of copper and zinc. Paraffin embedded segments (4 μm of thickness) of thoracic aorta were analyzed using a 10 keV incident monochromatic X-ray beam focusing on a spot size of 0.3 μm × 0.2 μm (horizontal × vertical). The X-ray spectrum was measured using an energy-dispersive silicon drift detector for elemental topography. Our results showed that phosphorus, sulfur, and zinc are predominately distributed in the vascular smooth muscle cells, whereas copper is dramatically accumulated in elastic laminae, indicating a preferential spatial association of copper on elastic laminae in aortic media. This finding sheds new light on the role of copper in elastic formation. Our studies also demonstrate that SRXRF allows for the visualization of trace elements in tissues and cells of rodent aorta with high spatial resolution and provides an opportunity to study the role of trace elements in vasculature.

  12. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    Energy Technology Data Exchange (ETDEWEB)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

    2014-10-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic

  13. Divergent role of nitric oxide in insulin-stimulated aortic vasorelaxation between low- and high-intrinsic aerobic capacity rats.

    Science.gov (United States)

    Crissey, Jacqueline M; Padilla, Jaume; Vieira-Potter, Victoria J; Thorne, Pamela K; Koch, Lauren G; Britton, Steven L; Thyfault, John P; Laughlin, M Harold

    2015-07-01

    Low-intrinsic aerobic capacity is associated with increased risk for cardiovascular and metabolic diseases and is a strong predictor of early mortality. The effects of intrinsic aerobic capacity on the vascular response to insulin are largely unknown. We tested the hypothesis that rats selectively bred for a low capacity to run (LCR) exhibit vascular dysfunction and impaired vascular reactivity to insulin compared to high capacity running (HCR) rats. Mature female LCR (n = 21) and HCR (n = 17) rats were maintained under sedentary conditions, and in vitro thoracic aortic vascular function was assessed. LCR exhibited greater body mass (13%), body fat (35%), and subcutaneous, perigonadal, and retroperitoneal adipose tissue mass, than HCR. During an intraperitoneal glucose tolerance test, glucose area under the curve (AUC) was not different but insulin AUC was 2-fold greater in LCR than HCR. Acetylcholine and insulin-stimulated aortic vasorelaxation was significantly greater in LCR (65.2 ± 3.8%, and 32.7 ± 4.1%) than HCR (55.0 ± 3.3%, and 16.7 ± 2.8%). Inhibition of nitric oxide synthase (NOS) with L-NAME entirely abolished insulin-mediated vasorelaxation in the aorta of LCR, with no effect in HCR. LCR rats exhibited greater expression of Insulin Receptor protein, lower Endothelin Receptor-A protein, a down-regulation of transcripts for markers of immune cell infiltration (CD11C, CD4, and F4/80) and up-regulation of pro-atherogenic inflammatory genes (VCAM-1 and MCP-1) in the aorta wall. Contrary to our hypothesis, low-aerobic capacity was associated with enhanced aortic endothelial function and NO-mediated reactivity to insulin, despite increased adiposity and evidence of whole body insulin resistance. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  14. Developmental programming of aortic and renal structure in offspring of rats fed fat-rich diets in pregnancy

    DEFF Research Database (Denmark)

    Armitage, James A.; Lakasing, Lorin; Taylor, Paul D.

    2005-01-01

    -Dawley rats fed a control diet (OC) or lard-rich diet (OHF) during pregnancy and suckling followed by a control diet post-weaning. To gain further insight, we assessed aortic reactivity and elasticity in an organ bath preparation and renal renin and Na+,K+-ATPase activity. Plasma aldosterone concentration...... programmes the development of increased blood pressure, insulin resistance, dyslipidaemia, obesity and mesenteric artery endothelial dysfunction in adult offspring. To further characterize the mechanism of hypertension in this model we have examined vascular and renal structure in adult offspring of Sprague...... systemic vascular changes in the offspring. Despite normal renal stereology, altered renal Na+,K+-ATPase and renin activity offers further insight into the mechanism underlying the increased blood pressure characteristic of this model....

  15. Vascular smooth muscle cells in Marfan syndrome aneurysm: the broken bricks in the aortic wall.

    Science.gov (United States)

    Perrucci, Gianluca L; Rurali, Erica; Gowran, Aoife; Pini, Alessandro; Antona, Carlo; Chiesa, Roberto; Pompilio, Giulio; Nigro, Patrizia

    2017-01-01

    Marfan syndrome (MFS) is a connective tissue disorder with multiple organ manifestations. The genetic cause of this syndrome is the mutation of the FBN1 gene, encoding the extracellular matrix (ECM) protein fibrillin-1. This genetic alteration leads to the degeneration of microfibril structures and ECM integrity in the tunica media of the aorta. Indeed, thoracic aortic aneurysm and dissection represent the leading cause of death in MFS patients. To date, the most effective treatment option for this pathology is the surgical substitution of the damaged aorta. To highlight novel therapeutic targets, we review the molecular mechanisms related to MFS etiology in vascular smooth muscle cells, the foremost cellular type involved in MFS pathogenesis.

  16. Telemetric ambulatory arterial stiffness index, a predictor of cardio-cerebro-vascular mortality, is associated with aortic stiffness-determining factors.

    Science.gov (United States)

    Li, Zhi-Yong; Xu, Tian-Ying; Zhang, Sai-Long; Zhou, Xiao-Ming; Xu, Xue-Wen; Guan, Yun-Feng; Lo, Ming; Miao, Chao-Yu

    2013-09-01

    Ambulatory arterial stiffness index (AASI) has been proposed as a new measure of arterial stiffness for predicting cardio-cerebro-vascular morbidity and mortality. However, there has been no research on the direct relationships between AASI and arterial stiffness-determining factors. We utilized beat-to-beat intra-aortic blood pressure (BP) telemetry to characterize AASI in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). By determination of aortic structural components and analysis of their correlations with AASI, we provided the first direct evidence for the associations between AASI and arterial stiffness-determining factors including the collagen content and collagen/elastin. Ambulatory arterial stiffness index was positively correlated with pulse pressure in both WKY and SHR, less dependent on BP and BP variability than pulse pressure, and relatively stable, especially the number of BP readings not less than ~36. The correlations between AASI and aortic components were comparable for various AASI values derived from BP readings not less than ~36. Not only AASI but also BP variability and pulse pressure demonstrated a direct relationship with arterial stiffness. These findings indicate AASI may become a routine measure in human arterial stiffness assessment. It is recommended to use a cluster of parameters such as AASI, BP variability, and pulse pressure for evaluating arterial stiffness. © 2013 John Wiley & Sons Ltd.

  17. Methanol extract of Sorbus commixta cortex prevents vascular inflammation in rats with a high fructose-induced metabolic syndrome.

    Science.gov (United States)

    Kang, Dae Gill; Sohn, Eun Jin; Lee, An Sook; Kim, Jin Sook; Lee, Dae Ho; Lee, Ho Sub

    2007-01-01

    Feeding high fructose (Frc) to rats induces a moderate increase in blood pressure, which is associated with insulin resistance. The present study was designed to evaluate the effect of the methanol extract of Sorbus commixta cortex (MSC) on vascular inflammation in a rat model of the metabolic syndrome induced by a high Frc-diet. Male Sprague-Dawley rats were divided into 4 groups and treated for 7 weeks as follows: 1) control, 2) high Frc-diet group, 3) Frc/MSC1 group; high Frc-diet group treated with MSC (100 mg/kg/day), and 4) Frc/MSC2 group; high Frc-diet group treated with MSC (200 mg/kg/day). High Frc-induced decreases of the expression level of aortic endothelial nitric oxide synthase (ecNOS) while the production of cyclic GMP (cGMP) was restored by treatment with MSC. On the contrary, increases of the expression level of endothelin-1 (ET-1) in the aorta, the transcription factor, the cytokine related with vascular inflammation, and the adhesion molecules were suppressed by MSC treatment. Moreover, MSC treatment was shown to lessen the thickening noted in the aortic intima and media of the high Frc-diet group. Our findings suggest that MSC may have an anti-vascular inflammatory effect on rats with a high Frc-induced metabolic syndrome.

  18. Open versus endovascular repair of abdominal aortic aneurysm: a survey of Canadian vascular surgeons.

    Science.gov (United States)

    Mastracci, Tara M; Clase, Catherine M; Devereaux, Philip J; Cinà, Claudio S

    2008-04-01

    The aim of this survey was to determine Canadian vascular surgeons' experience with elective endovascular aortic repair (EVAR) and traditional open repair and their interest in participating in an expertise- based randomized controlled trial (RCT) as opposed to a conventional RCT comparing these 2 procedures. A single-page questionnaire was developed and sent by fax, email or post to all vascular surgeons in Canada. Nonresponders were recontacted on 2 additional occasions to improve the response rate. The questionnaire had 2 sections. The first inquired about current and past practice patterns, including experience in both open and endovascular techniques. The second investigated the surgeons' belief in the value of open as opposed to endovascular repair and the value of expertise-based RCT methodology; it also canvassed their interest in participating in a future trial. Definitions of expertise in open and endovascular repair were drawn from the published literature. Criteria to determine the feasibility of conducting an expertise-based RCT were established a priori. The questionnaire was sent to 259 surgeons who appeared in multiple vascular surgery databases, and the overall response rate was 56% (95% confidence interval [CI] 50%-62%). The mean career experience was 406 cases (standard deviation [SD] 359) for conventional open abdominal aortic aneurysm (AAA) repair and 24 cases (SD 48) for endovascular repair. Of the responding surgeons, 51% (95% CI 41%-60%) ranked conventional open repair as "probably superior." Respondents were equally interested in participating in an RCT using either expertise-based methodology (54%, 95% CI 44%-63%) or conventional design (51%, 95% CI 41%-60%). Uncertainty exists among vascular surgeons in Canada as to the role of endovascular surgery in the repair of AAA. A national RCT comparing open with endovascular repair in the elective setting is potentially feasible with either expertise-based or conventional design. Increases in the

  19. Aerobic Swim Training Restores Aortic Endothelial Function by Decreasing Superoxide Levels in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Camila P. Jordão

    Full Text Available OBJECTIVE: We aimed to determine whether aerobic training decreases superoxide levels, increases nitric oxide levels, and improves endothelium-dependent vasodilation in the aortas of spontaneously hypertensive rats. METHODS: Spontaneously hypertensive rats (SHR and Wistar Kyoto rats (WKY were distributed into 2 groups: sedentary (SHRsd and WKYsd, n=10 each and swimming-trained (SHRtr, n=10 and WKYtr, n=10, respectively. The trained group participated in training sessions 5 days/week for 1 h/day with an additional work load of 4% of the animal’s body weight. After a 10-week sedentary or aerobic training period, the rats were euthanized. The thoracic aortas were removed to evaluate the vasodilator response to acetylcholine (10-10 to 10-4 M with or without preincubation with L-NG-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10-4 M in vitro. The aortic tissue was also used to assess the levels of the endothelial nitric oxide synthase and nicotinamide adenine dinucleotide oxidase subunit isoforms 1 and 4 proteins, as well as the superoxide and nitrite contents. Blood pressure was measured using a computerized tail-cuff system. RESULTS: Aerobic training significantly increased the acetylcholine-induced maximum vasodilation observed in the SHRtr group compared with the SHRsd group (85.9±4.3 vs. 71.6±5.2%. Additionally, in the SHRtr group, superoxide levels were significantly decreased, nitric oxide bioavailability was improved, and the levels of the nicotinamide adenine dinucleotide oxidase subunit isoform 4 protein were decreased compared to the SHRsd group. Moreover, after training, the blood pressure of the SHRtr group decreased compared to the SHRsd group. Exercise training had no effect on the blood pressure of the WKYtr group. CONCLUSIONS: In SHR, aerobic swim training decreased vascular superoxide generation by nicotinamide adenine dinucleotide oxidase subunit isoform 4 and increased nitric oxide bioavailability, thereby improving

  20. Aerobic Swim Training Restores Aortic Endothelial Function by Decreasing Superoxide Levels in Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Jordão, Camila P; Fernandes, Tiago; Tanaka, Leonardo Yuji; Bechara, Luiz R Grassmann; de Sousa, Luis Gustavo Oliveira; Oliveira, Edilamar M; Ramires, Paulo Rizzo

    2017-05-01

    We aimed to determine whether aerobic training decreases superoxide levels, increases nitric oxide levels, and improves endothelium-dependent vasodilation in the aortas of spontaneously hypertensive rats. Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were distributed into 2 groups: sedentary (SHRsd and WKYsd, n=10 each) and swimming-trained (SHRtr, n=10 and WKYtr, n=10, respectively). The trained group participated in training sessions 5 days/week for 1 h/day with an additional work load of 4% of the animal's body weight. After a 10-week sedentary or aerobic training period, the rats were euthanized. The thoracic aortas were removed to evaluate the vasodilator response to acetylcholine (10-10 to 10-4 M) with or without preincubation with L-NG-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10-4 M) in vitro. The aortic tissue was also used to assess the levels of the endothelial nitric oxide synthase and nicotinamide adenine dinucleotide oxidase subunit isoforms 1 and 4 proteins, as well as the superoxide and nitrite contents. Blood pressure was measured using a computerized tail-cuff system. Aerobic training significantly increased the acetylcholine-induced maximum vasodilation observed in the SHRtr group compared with the SHRsd group (85.9±4.3 vs. 71.6±5.2%). Additionally, in the SHRtr group, superoxide levels were significantly decreased, nitric oxide bioavailability was improved, and the levels of the nicotinamide adenine dinucleotide oxidase subunit isoform 4 protein were decreased compared to the SHRsd group. Moreover, after training, the blood pressure of the SHRtr group decreased compared to the SHRsd group. Exercise training had no effect on the blood pressure of the WKYtr group. In SHR, aerobic swim training decreased vascular superoxide generation by nicotinamide adenine dinucleotide oxidase subunit isoform 4 and increased nitric oxide bioavailability, thereby improving endothelial function.

  1. Angiotensin-converting enzyme inhibitor increases angiotensin type 1A receptor gene expression in aortic smooth muscle cells of spontaneously hypertensive rats.

    Science.gov (United States)

    Negoro, N; Kanayama, Y; Iwai, J; Umetani, N; Nishimura, M; Konishi, Y; Okamura, M; Inoue, T; Takeda, T

    1994-04-12

    To examine the regulation of angiotensin receptors in vascular smooth muscle cells, we studied the effects of antihypertensive drugs on angiotensin type 1A (AT1A) receptor gene expression in aortic smooth muscle cells (ASMCs) from spontaneously hypertensive rats (SHRs) using both ribonuclease protection assay and reverse-transcription polymerase chain reaction. An increase in AT1A receptor gene expression in ASMCs of SHRs was induced by treatment with an angiotensin converting enzyme inhibitor (enalapril) for 2 weeks and 4 weeks, but not by other types of antihypertensive drugs such as alpha-blocker (doxazosin), alpha, beta-blocker (arotinolol), Ca antagonist (nicardipine) or vascular smooth muscle relaxant (hydralazine). Since all antihypertensive drugs lowered the blood pressure of the rats almost equally, our results suggest that AT1A receptor gene expression in ASMCs of SHRs may be regulated by the vascular renin-angiotensin system.

  2. Chemerin reduces vascular nitric oxide/cGMP signalling in rat aorta: a link to vascular dysfunction in obesity?

    Science.gov (United States)

    Neves, Karla Bianca; Lobato, Núbia S; Lopes, Rhéure Alves Moreira; Filgueira, Fernando P; Zanotto, Camila Ziliotto; Oliveira, Ana Maria; Tostes, Rita C

    2014-07-01

    The adipokine chemerin has been implicated in cardiovascular complications associated with obesity and the metabolic syndrome. Chemerin has direct effects on the vasculature, augmenting vascular responses to contractile stimuli. As NO/cGMP signalling plays a role in vascular dysfunction associated with obesity and the metabolic syndrome, we hypothesized that chemerin induces vascular dysfunction by decreasing NO/cGMP signalling. Aortic rings from male Wistar rats (10-12 weeks of age) were incubated with chemerin (0.5 or 5 ng/ml for 1 h) or vehicle and isometric tension was recorded. Vasorelaxation in response to ACh (acetylcholine), SNP (sodium nitroprusside) and BAY 412272 [an sGC (soluble guanylate cyclase) stimulator] were decreased in chemerin-treated vessels. The NOS (NO synthase) cofactor BH4 (tetrahydrobiopterin), an O2- (superoxide anion) scavenger (tiron) and a SOD (superoxide dismutase) mimetic (tempol) abolished the effects of chemerin on ACh-induced vasodilation. eNOS (endothelial NOS) phosphorylation, determined by Western blotting, was increased in chemerin-treated vessels; however, the enzyme was mainly in the monomeric form, with decreased eNOS dimer/monomer ratio. Chemerin decreased the mRNA levels of the rate-limiting enzyme for BH4 biosynthesis GTP cyclohydrolase I. Chemerin-incubated vessels displayed decreased NO production, along with increased ROS (reactive oxygen species) generation. These effects were abrogated by BH4, tempol and L-NAME (NG-nitro-L-arginine methyl ester). sGC protein expression and cGMP levels were decreased in chemerin-incubated vessels. These results demonstrate that chemerin reduces NO production, enhances NO breakdown and also decreases NO-dependent cGMP signalling, thereby reducing vascular relaxation. Potential mechanisms mediating the effects of chemerin in the vasculature include eNOS uncoupling, increased O2- generation and reduced GC activity.

  3. Effect of ruthenium red, a ryanodine receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.

    Science.gov (United States)

    Jain, Swati; Sharma, Bhupesh

    2016-10-01

    Diabetes mellitus is considered as a main risk factor for vascular dementia. In the past, we have reported the induction of vascular dementia by experimental diabetes. This study investigates the efficacy of a ruthenium red, a ryanodine receptor antagonist and pioglitazone in the pharmacological interdiction of pancreatectomy diabetes (PaD) induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. PaD rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with an increase in brain inflammation, oxidative stress and calcium. Administration of ruthenium red and pioglitazone has significantly attenuated PaD induced impairment of learning, memory, blood brain barrier permeability, endothelial function and biochemical parameters. It may be concluded that ruthenium red, a ryanodine receptor antagonist and pioglitazone, a PPAR-γ agonist may be considered as potent pharmacological agent for the management of PaD induced endothelial dysfunction and subsequent vascular dementia. Ryanodine receptor may be explored further for their possible benefits in vascular dementia. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Antihypertensive and vascular remodelling effects of the imperatorin derivative OW1 in renovascular hypertension rats.

    Science.gov (United States)

    Zhou, Nan; Wang, Tao; Song, Jia; He, Huaizhen; He, Jianyu; He, Langchong

    2014-08-01

    OW1 is a novel imperatorin derivative that exhibits vasodilator activity. In the present study, the antihypertensive effect of and inhibition of vascular remodelling by OW1 were investigated in two-kidney, one-clip (2K1C) renovascular hypertensive rats. Rats were subjected to the 2K1C procedure and treated with OW1 (40 or 80 mg/kg per day) for 8 weeks. Blood pressure was measured in conscious rats. Microalbumin (mALB) and total protein (U-TP) concentrations were determined in the urine, as were plasma concentrations of angiotensin (Ang) II, calcitonin gene-related peptide (CGRP) and angiotensin-converting enzyme 1 (ACE). The unclipped kidney was stained with haematoxylin and eosin and Masson trichrome, whereas aortic sections were stained with Masson trichrome. In addition, OW1-induced vasodilatation was evaluated in vitro in rat mesenteric and renal arteries. Immunohistochemical analysis was used to quantify collagen I and III expression. OW1 relaxed rat mesenteric and renal arterial rings in vitro. Treatment of 2K1C hypertensive rats with OW1 (40 and 80 mg/kg per day) for 8 weeks significantly decreased blood pressure. In addition, OW1 reduced plasma AngII and ACE concentrations and increased plasma CGRP concentrations. At 80 mg/kg per day, OW1 decreased blood urea nitrogen, mALB and U-TP levels. Histological analysis revealed that OW1 reduced renal arteriolar thickness and relieved the structural hypertrophic arteries. Moreover, OW1 had an inhibitory effect on vascular remodelling and renal lesions in hypertensive rats. In conclusion, the results suggest that OW1 could potentially be a novel candidate for hypertension intervention. © 2014 Wiley Publishing Asia Pty Ltd.

  5. Sex differences in aortic root and vascular anatomy in patients undergoing transcatheter aortic valve implantation: A computed-tomographic study.

    Science.gov (United States)

    Hamdan, Ashraf; Barbash, Israel; Schwammenthal, Ehud; Segev, Amit; Kornowski, Ran; Assali, Abid; Shaviv, Ella; Fefer, Paul; Goitein, Orly; Konen, Eli; Guetta, Victor

    Very little data exist on the impact of sex on aortic and arterial anatomy as relevant for transcatheter aortic valve implantation (TAVI). To investigate whether patients with severe aortic stenosis (AS) referred for TAVI display sex-specific differences in aortic root and ilio-femoral artery size. In 506 patients referred for pre-procedural CT evaluation before TAVI we performed a detailed assessment of aortic root anatomy: size of the annulus and the sinus of Valsalva (SoV), diameter of the sino-tubular junction (STJ), and distance of the coronary artery ostia to the aortic annulus plane; we also determined the dimensions of aorta, subclavian, and ilio-femoral arteries. Women had significantly smaller aortic root dimensions (annulus mean diameter: 22.9 ± 2.2 mm vs. 25.7 ± 2.7 mm, SoV mean diameter: 31.8 ± 4.2 mm vs. 36.3 ± 3.8 mm, STJ mean diameter: 26.3 ± 3.4 mm vs. 29.8 ± 4.2 mm) and lower left and right coronary artery ostia take-off (12.3 ± 2.4 vs. 14.1 ± 2.9 mm; 14.8 ± 2.6 vs. 17.1 ± 3.2 mm, respectively) than men (P < 0.001 for all), even after adjustment for their smaller body surface area (BSA) and height. Dimensions of the ascending aorta, subclavian and ilio-femoral arteries were also significantly smaller in women, but not when adjusted for BSA. Women with severe AS had smaller aortic root dimensions even after correcting for their smaller body size and height, reflecting a sex-specific difference. In contrast, sex-related differences in aortic, subclavian, and ilio-femoral dimensions were fully explained by the smaller BSA of women. Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  6. Effect of water fluoridation on the development of medial vascular calcification in uremic rats.

    Science.gov (United States)

    Martín-Pardillos, Ana; Sosa, Cecilia; Millán, Ángel; Sorribas, Víctor

    2014-04-06

    Public water fluoridation is a common policy for improving dental health. Fluoride replaces the hydroxyls of hydroxyapatite, thereby improving the strength of tooth enamel, but this process can also occur in other active calcifications. This paper studies the effects of water fluoridation during the course of vascular calcification in renal disease. The effect of fluoride was studied in vitro and in vivo. Rat aortic smooth muscle cells were calcified with 2mM Pi for 5 days. Fluoride concentrations of 5-10 μM--similar to those found in people who drink fluoridated water--partially prevented calcification, death, and osteogene expression in vitro. The anticalcifying mechanism was independent of cell activity, matrix Gla protein, and fetuin A expressions, and it exhibited an IC50 of 8.7 μM fluoride. In vivo, however, fluoridation of drinking water at 1.5mg/L (concentration recommended by the WHO) and 15 mg/L dramatically increased the incipient aortic calcification observed in rats with experimental chronic kidney disease (CKD, 5/6-nephrectomy), fed a Pi-rich fodder (1.2% Pi). Fluoride further declined the remaining renal function of the CKD animals, an effect that most likely overwhelmed the positive effect of fluoride on calcification in vitro. Ultrastructural analysis revealed that fluoride did not modify the Ca/P atomic ratio, but it was incorporated into the lattice of in vivo deposits. Fluoride also converted the crystallization pattern from plate to rode-like structures. In conclusion, while fluoride prevents calcification in vitro, the WHO's recommended concentrations in drinking water become nephrotoxic to CKD rats, thereby aggravating renal disease and making media vascular calcification significant. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. [Right-side aortic arch with aberrant left subclavian artery and Kommerell's diverticulum. A cause of vascular ring].

    Science.gov (United States)

    Tamayo-Espinosa, Tania; Erdmenger-Orellana, Julio; Becerra-Becerra, Rosario; Balderrabano-Saucedo, Norma; Segura-Standford, Begoña

    The right-side aortic arch may be associated with aberrant left subclavian artery, in some cases this artery originates from an aneurismal dilation of the aorta called Kommerell's diverticulum. A report is presented on 2 cases of vascular ring formed by a right-side aortic arch, anomalous left subclavian artery, Kommerell's diverticulum and left patent ductus arteriosus. A review the literature was also performed as regards the embryological development and the imaging methods used to help in the diagnosis of this rare vascular anomaly. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  8. Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats

    OpenAIRE

    Zhou, Wugang; Hong, Mona; Zhang, Ke; Chen, Dongrui; Han, Weiqing; Shen, Weili; Zhu, Dingliang; Gao, Pingjin

    2014-01-01

    OBJECTIVES: This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR). METHODS: The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO) was measured in human aortic endothelial cells (HAECs) by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d⁻¹), arotinolol (30 mg·kg-1·d⁻¹) for 8 weeks. Ce...

  9. Pig specific vascular anatomy allows acute infrarenal aortic occlusion without hind limb ischemia and stepwise occlusion without clinical signs.

    Science.gov (United States)

    Haacke, N; Unger, J K; Haidenhein, C; Russ, M; Hiebl, B; Niehues, S M

    2011-01-01

    In a porcine, aortic graft model we found 5 animals to develop and survive unnoticed, complete infrarenal aortic occlusion and 2 pigs with an acute occlusion but rather unspecific clinical symptoms. We investigated the pigs' vascular system to classify the anatomic capabilities to compensate for an acute abdominal aortic occlusion. Retrospective analysis of CT scans and clinical data to specify unexpected results in a case series of infrarenal occlusion in a porcine model. Collaborative study of experimental and clinical departments. Fifteen healthy female minipigs. All pigs underwent an infrarenal aortic graft intervention. Anesthesia and perioperative management of the animals were preformed along the standard operating procedures of the local Department of Experimental Medicine. All animals received perioperative antibiotics, ASS, and carprofen for postoperative analgesia. Arterial pressure, heart rate, body temperature, and diuresis were monitored during surgery and therapeutic interventions. Contrast media based computed tomography (CT) with total body scans were performed at 1, 4, 10, 12 weeks after surgery. Comparable scans of cardiovascular healthy subjects (humans and pigs) and patients with a Leriche's syndrome were analyzed. Neither acute (within the first 12 h after surgery) nor stepwise total aortic occlusion show unmistakable clinical signs. In pigs, the epigastric artery (EGA) - which is in connection with suprarenal lumbal arteries, subclavian and external iliac artery - is highly developed associated to the high number of mammary glands of about 7 on one side. In humans, the ratio of aortic to EGA-diameter is 1 : 0.15. In minipigs we found a ratio of 1 : 0.43 which changed during aortic occlusion resulting in a ratio of 1 : 0.58. Pigs with a slowly developing occlusion demonstrated an enlargement of the ureteric artery of about 210% completing a sufficient collateral system. While in the human Leriche's syndrome months are needed to enlarge the

  10. A new technique for vascular access management in transcatheter aortic valve implantation.

    Science.gov (United States)

    Sharp, Andrew S P; Michev, Iassen; Maisano, Francesco; Taramasso, Maurizio; Godino, Cosmo; Latib, Azeem; Denti, Paulo; Dorigo, Enrica; Giacomini, Andrea; Iaci, Giuseppe; Manca, Mario; Ielasi, Alfonso; Montorfano, Matteo; Alfieri, Ottavio; Colombo, Antonio

    2010-04-01

    To describe results from a novel percutaneous technique designed to minimize the risk of hemorrhage in the event of a major complication during transcatheter aortic valve implantation. Vascular access management is a major challenge in transfemoral TAVI due to the large introducer sheathes required. Fifty-two pts underwent TAVI between November 2007 and March 2009. Of these, 37 received an Edwards-Sapien Valve (23 mm valve: 17/37; 26 mm valve: 20/37) whilst 15 patients received a CoreValve (26 mm valve: 6/15; 29 mm valve: 9/15). Using a crossover technique, the opposing femoral artery was cannulated with a 7Fr long sheath. This allowed contralateral passage of a balloon and inflation in the proximal iliac. The sheath was then removed and Prostar sutures tied in a dry field. Balloon optimization of the puncture site was performed as required. In three subjects, elective surgical repair was undertaken due to excessive femoral arterial calcification. In the remaining 49, the crossover technique was employed and closed with two Prostar devices (Edwards-Sapien) or one (CoreValve). There were serious "on-table" complications in seven patients, six due to the large introducer sheathes used in the TAVI procedure-iliac avulsion, two iliac dissections, iliac perforation, common femoral perforation and scrotal hematoma. All were repaired safely by combined surgical and endovascular techniques, using the crossover technique to ensure patient stability. All made a good recovery and were independently ambulant at discharge. Using crossover balloon inflation as an adjunct to Prostar closure may be helpful for managing TAVI vascular access sites. (c) 2009 Wiley-Liss, Inc.

  11. Activation of Vascular Smooth Muscle Parathyroid Hormone Receptor Inhibits Wnt/β-Catenin Signaling and Aortic Fibrosis in Diabetic Arteriosclerosis

    Science.gov (United States)

    Cheng, Su-Li; Shao, Jian-Su; Halstead, Linda R.; Distelhorst, Kathryn; Sierra, Oscar; Towler, Dwight A.

    2010-01-01

    Rationale Vascular fibrosis and calcification contribute to diabetic arteriosclerosis, impairing Windkessel physiology necessary for distal tissue perfusion. Wnt family members up-regulated in arteries by the low-grade inflammation of “diabesity” -- stimulate type I collagen expression and osteogenic mineralization of mesenchymal progenitors via β-catenin. Conversely, parathyroid hormone (PTH) inhibits aortic calcification in LDLR (low density lipoprotein receptor)-deficient mice fed high fat diabetogenic diets (HFD). Objective We wished to determine the impact of vascular PTH receptor (PTH1R) activity on arteriosclerotic Wnt/β-catenin signaling in vitro and in vivo. We generated SM-caPTH1R transgenic mice, a model in which the constitutively active PTH1R variant H223R (caPTH1R) is expressed only in the vasculature. Methods and Results The caPTH1R inhibited Wnt/β-catenin signaling, collagen production, and vascular smooth muscle cell (VSMC) proliferation and calcification in vitro. Transgenic SM-caPTH1R;LDLR+/− mice fed HFD develop “diabesity,” with no improvements in fasting serum glucose, cholesterol, weight, body composition, or bone mass vs. LDLR+/− siblings. SM-caPTH1R down-regulated aortic Col1A1, Runx2, and Nox1 expression without altering TNF, Msx2, Wnt7a/b, or Nox4. The SM-caPTH1R transgene decreased aortic β-catenin protein accumulation and signaling in diabetic LDLR+/− mice. Levels of aortic superoxide -- a precursor of peroxide that activates pro-MMP9 and osteogenic signaling in VSMCs -- were suppressed by the SM-caPTH1R transgene. Aortic calcification, collagen accumulation, and wall thickness were concomitantly reduced, enhancing vessel distensibility. Conclusions Cell-autonomous VSMC PTH1R activity inhibits arteriosclerotic Wnt/β-catenin signaling and reduces vascular oxidative stress, thus limiting aortic type I collagen and calcium accrual in diabetic LDLR-deficient mice. PMID:20489161

  12. 3D bioprinting of biomimetic aortic vascular constructs with self-supporting cells.

    Science.gov (United States)

    Kucukgul, Can; Ozler, S Burce; Inci, Ilyas; Karakas, Ezgi; Irmak, Ster; Gozuacik, Devrim; Taralp, Alpay; Koc, Bahattin

    2015-04-01

    Cardiovascular diseases are the leading cause of deaths throughout the world. Vascular diseases are mostly treated with autografts and blood vessel transplantations. However, traditional grafting methods have several problems including lack of suitable harvest sites, additional surgical costs for harvesting procedure, pain, infection, lack of donors, and even no substitutes at all. Recently, tissue engineering and regenerative medicine approaches are used to regenerate damaged or diseased tissues. Most of the tissue engineering investigations have been based on the cell seeding into scaffolds by providing a suitable environment for cell attachment, proliferation, and differentiation. Because of the challenges such as difficulties in seeding cells spatially, rejection, and inflammation of biomaterials used, the recent tissue engineering studies focus on scaffold-free techniques. In this paper, the development of novel computer aided algorithms and methods are developed for 3D bioprinting of scaffold-free biomimetic macrovascular structures. Computer model mimicking a real human aorta is generated using imaging techniques and the proposed computational algorithms. An optimized three-dimensional bioprinting path planning are developed with the proposed self-supported model. Mouse embryonic fibroblast (MEF) cell aggregates and support structures (hydrogels) are 3D bioprinted layer-by-layer according to the proposed self-supported method to form an aortic tissue construct. © 2014 Wiley Periodicals, Inc.

  13. Detection of histidine decarboxylase in rat aorta and cultured rat aortic smooth muscle cells.

    Science.gov (United States)

    Tippens, A S; Davis, S V; Hayes, J R; Bryda, E C; Green, T L; Gruetter, C A

    2004-08-01

    Having previously demonstrated release of histamine from mast-cell-deficient rat aorta, the objective of this study was to determine and localize histamine synthesis capability in the aorta by detecting histidine decarboxylase (HDC), the enzyme that catalyzes histamine formation. Experiments were conducted with nested reverse transcription-polymerase chain reaction (nRT-PCR) to detect HDC mRNA and with immunofluorescence and western blot analysis to detect HDC protein in rat aorta, cultured rat aortic smooth muscle (RASMC) and endothelial cells (RAEC). Gel electrophoresis of nRT-PCR products indicated HDC mRNA in liver, aorta and RASMC but not in RAEC or kidney. Sequence analysis confirmed that the band observed in RASMC was the target HDC amplicon. Immunofluorescence indicated the presence of HDC protein in RASMC and not in RAEC. Western Blot analysis revealed HDC protein (55 kDa) in liver, aorta, RASMC but not in RAEC or kidney. The results of this study are the first to demonstrate the presence of HDC mRNA and protein in rat aorta and more specifically in RASMC, indicative of their capability to synthesize histamine. Copyright 2004 Birkhäuser Verlag, Basel

  14. Intensity of swimming exercise influences aortic reactivity in rats

    Directory of Open Access Journals (Sweden)

    A.F. Brito

    2015-11-01

    Full Text Available Exercise is known to cause a vasodilatory response; however, the correlation between the vasorelaxant response and different training intensities has not been investigated. Therefore, this study evaluated the vascular reactivity and lipid peroxidation after different intensities of swimming exercise in rats. Male Wistar rats (aged 8 weeks; 250-300 g underwent forced swimming for 1 h whilst tied to loads of 3, 4, 5, 6, and 8% of their body weight, respectively (groups G3, G4, G5, G6 and G8, respectively; n=5 each. Immediately after the test, the aorta was removed and suspended in an organ bath. Cumulative relaxation in response to acetylcholine (10−12-10−4 M and contraction in response to phenylephrine (10−12-10−5 M were measured. Oxidative stress was estimated by determining malondialdehyde concentration. The percentages of aorta relaxation were significantly higher in G3 (7.9±0.20, G4 (7.8±0.29, and G5 (7.9±0.21, compared to the control group (7.2±0.04, while relaxation in the G6 (7.4±0.25 and G8 (7.0±0.06 groups was similar to the control group. In contrast, the percentage of contraction was significantly higher in G6 (8.8 ±0.1 and G8 (9.7±0.29 compared to the control (7.1±0.1, G3 (7.3±0.2, G4 (7.2±0.1 and G5 (7.2±0.2% groups. Lipid peroxidation levels in the aorta were similar to control levels in G3, G4 and G5, but higher in G6 and G8, and significantly higher in G8 (one-way ANOVA. These results indicate a reduction in vasorelaxing activity and an increase in contractile activity in rat aortas after high-intensity exercise, followed by an increase in lipid peroxidation.

  15. Myocardial infarction with aortic banding - A combined rat model of heart failure

    NARCIS (Netherlands)

    Anthonio, RL; vanVeldhuisen, DJ; vanBekkum, C; deBoer, E; vanGilst, WH

    The effect of additional abdominal aortic banding on parameters of heart failure was studied in male Wistar rats with myocardial infarction. Contractile function was studied 8-9 weeks after operation, with an isoprenaline dose response protocol, in a retrograde Langendorff perfusion. Also, plasma

  16. Diazoxide protects rat vascular endothelial cells against hypoxia and cold-induced damage.

    Science.gov (United States)

    Zhang, Lian-Cheng; Huang, Zhao; Li, Pei-Bing; Nie, Hong-Jing; Deng, Bing-Nan; Duan, Rui-Feng; Xiao, Zhong-Hai; Peng, Hui; Feng, Hong; Liu, Wei

    2017-06-01

    The present study aimed to examine the effects of hypoxia and cold on vascular endothelial cells (VECs), as well as the protective ability of novel VECs-protective drugs against these injuries. A rat model simulating exposure to hypoxia and cold at high altitude environments was established. Based on these animal experiments, rat aortic VECs were established as injury models and exposed to hypoxia and/or adrenaline (ADR) in vitro. The results revealed that hypoxia significantly altered the levels of nitric oxide and vascular endothelial growth factor, while the cold temperature significantly increased the release of ADR and noradrenaline. Exposure to hypoxia combined with cold temperature significantly affected all these indices. In vitro experiments demonstrated that hypoxia, ADR (which was used to simulate cold in the animal experiments) and the combination of the two factors resulted in damage to the VECs and endothelial dysfunction. In addition, the results also showed that diazoxide, a highly selective mitoKATP opener, protected VECs against these injuries. In conclusion, hypoxia and cold temperature induced endothelial cell dysfunction and endocrine disorders, respectively. Improving endothelial function using diazoxide may be an effective therapeutic strategy in patients with altitude-associated disorders. However, the potential for clinical application requires further study.

  17. Safety and efficacy of using the Viabahn endoprosthesis for percutaneous treatment of vascular access complications after transfemoral aortic valve implantation

    DEFF Research Database (Denmark)

    De Backer, Ole; Arnous, Samer; Sandholt, Benjamin

    2015-01-01

    Vascular access complications (VACs) remain one of the biggest challenges when performing transcatheter aortic valve implantation (TAVI). This study aimed to investigate the short- and medium-term safety and efficacy of the Viabahn endoprosthesis (Gore, Flagstaff, AZ) when used to treat TAVI......-induced vascular injury. Over a 40-month period, 354 patients underwent true percutaneous transfemoral (TF)-TAVI using a CoreValve and Prostar-XL closure system; this was our study population. A VAC leading to acute intervention occurred in 72 patients (20.3%) - of these, 18 were managed by balloon angioplasty, 48...... stenting versus patients without vascular complications. Two patients (4.5%) presented with new-onset claudication; one of them had the stent implanted covering the deep femoral artery (DFA). At medium-term follow-up (median 372 days; range 55 to 978 days) duplex ultrasound showed 100% patency...

  18. Atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model

    Science.gov (United States)

    Oberkersch, Roxana; Maccari, Francesca; Bravo, Alicia I; Volpi, Nicola; Gazzaniga, Silvina; Calabrese, Graciela C

    2014-01-01

    Proteoglycan accumulation within the arterial intima has been implicated in atherosclerosis progression in humans. Nevertheless, hypercholesterolaemia is unable to induce intimal thickening and atheroma plaque development in rats. The study was performed to analyse proteoglycans modifications in rats fed with a high-cholesterol diet to understand whether vascular wall remodelling protects against lesions. Sections obtained from rat aortas showed normal features, in intimal-to-media ratio and lipid accumulation. However, focal endothelial hyperplasia and neo-intima rearrangement were observed in high-cholesterol animals. Besides, hypercholesterolaemia induced an inflammatory microenviroment. We determined the expression of different proteoglycans from aortic cells by Western blot and observed a diminished production of decorin and biglycan in high-cholesterol animals compared with control (P < 0.01 and P < 0.05, respectively). Versican was increased in high-cholesterol animals (P < 0.05), whereas perlecan production showed no differences. No modification of the total content of glycosaminoglycans (GAGs) was found between the two experimental groups. In contrast, the chondroitin sulphate/dermatan sulphate ratio was increased in the high-cholesterol group as compared to the control (0.56 and 0.34, respectively). Structural alterations in the disaccharide composition of galactosaminoglycans were also detected by HPLC, as the ratio of 6-sulphate to 4-sulphate disaccharides was increased in high-cholesterol animals (P < 0.05). Our results suggest that attenuation of decorin and biglycan expression might be an effective strategy to inhibit the first step in atherogenesis, although specific GAG structural modification associated with the development of vascular disease took place. Results emphasize the potential application of therapies based on vascular matrix remodelling to treat atherosclerosis. PMID:24602133

  19. Alteration of cardiac ACE2/Mas expression and cardiac remodelling in rats with aortic constriction.

    Science.gov (United States)

    Zhang, Yanling; Li, Bing; Wang, Bingxiangi; Zhang, Jingjun; Wu, Junyan; Morgan, Trefor

    2014-12-31

    The recent discovery of the new components of the renin-angiotensin system (RAS) suggests the importance of the maintenance of cardiovascular structure and functions. To assess the role of the angiotensin-converting enzyme 2 (ACE2)-Mas receptor axis in the regulation of cardiac structure and function, the present work investigated the expression of ACE2 and Mas receptor in the heart in the cardiac remodeling that occurs in aortic constricted rats. Partial abdominal aortic ligation was carried out in Sprague-Dawley rats. Angiotensin AT1 receptor blockade and ACE inhibition were achieved by losartan and enalapril treatment, respectively. Results showed that aortic constriction increased left ventricular hypertrophy, fibrosis, mean arterial pressure (MAP), plasma renin activity (PRA) and cardiac ACE levels, but decreased the expression of cardiac ACE2 and Mas receptor. Losartan treatment significantly decreased MAP, left ventricle hypertrophy (LVH), fibrosis, and increased cardiac ACE2 and Mas expression. Enalapril also improved the cardiac parameters with a rise in cardiac ACE2, but did not change the Mas level. In conclusion, aortic constriction results in cardiac hypertrophy, fibrosis and a rise of cardiac ACE expression. Both AT1 receptor blocker and ACE inhibitor play a cardioprotective role in aortic constriction. However, AT1 receptor blocker particularly promotes cardiac ACE2 and Mas receptor levels. ACE inhibitor is associated with the inhibition of ACE and normalization of cardiac ACE2 activity.

  20. Reactivity of the isolated perfused rat tail vascular bed

    Directory of Open Access Journals (Sweden)

    A.S. França

    1997-07-01

    Full Text Available Isolated segments of the perfused rat tail artery display a high basal tone when compared to other isolated arteries such as the mesenteric and are suitable for the assay of vasopressor agents. However, the perfusion of this artery in the entire tail has not yet been used for functional studies. The main purpose of the present study was to identify some aspects of the vascular reactivity of the rat tail vascular bed and validate this method to measure vascular reactivity. The tail severed from the body was perfused with Krebs solution containing different Ca2+ concentrations at different flow rates. Rats were anesthetized with sodium pentobarbital (65 mg/kg and heparinized (500 U. The tail artery was dissected near the tail insertion, cannulated and perfused with Krebs solution plus 30 µM EDTA at 36oC and 2.5 ml/min and the procedures were started after equilibration of the perfusion pressure. In the first group a dose-response curve to phenylephrine (PE (0.5, 1, 2 and 5 µg, bolus injection was obtained at different flow rates (1.5, 2.5 and 3.5 ml/min. The mean perfusion pressure increased with flow as well as PE vasopressor responses. In a second group the flow was changed (1.5, 2, 2.5, 3 and 3.5 ml/min at different Ca2+ concentrations (0.62, 1.25, 2.5 and 3.75 mM in the Krebs solution. Increasing Ca2+ concentrations did not alter the flow-pressure relationship. In the third group a similar protocol was performed but the rat tail vascular bed was perfused with Krebs solution containing PE (0.1 µg/ml. There was an enhancement of the effect of PE with increasing external Ca2+ and flow. PE vasopressor responses increased after endothelial damage with air and CHAPS, suggesting an endothelial modulation of the tone of the rat tail vascular bed. These experiments validate the perfusion of the rat tail vascular bed as a method to investigate vascular reactivity

  1. A multimodality vascular imaging phantom of an abdominal aortic aneurysm with a visible thrombus

    Energy Technology Data Exchange (ETDEWEB)

    Allard, Louise; Chayer, Boris; Qin Zhao [Laboratory of Biorheology and Medical Ultrasonics, Research Center, University of Montreal Hospital (CRCHUM), Quebec H2L 2W5 (Canada); Soulez, Gilles [Department of Radiology, University of Montreal Hospital (CHUM), Quebec H2L 2M1 (Canada); Department of Radiology, Radio-Oncology and Nuclear Medicine, University of Montreal, Quebec H3T 1J4 (Canada); Institute of Biomedical Engineering, University of Montreal, Quebec H3T 1J4 (Canada); Roy, David [Institute of Biomedical Engineering, University of Montreal, Quebec H3T 1J4 (Canada); Cloutier, Guy [Laboratory of Biorheology and Medical Ultrasonics, Research Center, University of Montreal Hospital (CRCHUM), Quebec H2L 2W5 (Canada); Department of Radiology, Radio-Oncology and Nuclear Medicine, University of Montreal, Quebec H3T 1J4 (Canada); Institute of Biomedical Engineering, University of Montreal, Quebec H3T 1J4 (Canada)

    2013-06-15

    Purpose: With the continuous development of new stent grafts and implantation techniques, it has now become technically feasible to treat abdominal aortic aneurysms (AAA) with challenging anatomy using endovascular repair with standard, fenestrated, or branched stent-grafts. In vitro experimentations are very useful to improve stent-graft design and conformability or imaging guidance for stent-graft delivery or follow-up. Vascular replicas also help to better understand the limitation of endovascular approaches in challenging anatomy and possibly improve surgical planning or training by practicing high risk clinical procedures in the laboratory to improve outcomes in the operating room. Most AAA phantoms available have a very basic anatomy, which is not representative of the clinical reality. This paper presents a method of fabrication of a realistic AAA phantom with a visible thrombus, as well as some mechanical properties characterizing such phantom. Methods: A realistic AAA geometry replica of a real patient anatomy taken from a multidetector computed tomography (CT) scan was manufactured. To demonstrate the multimodality imaging capability of this new phantom with a thrombus visible in magnetic resonance (MR) angiography, CT angiography (CTA), digital subtraction angiography (DSA), and ultrasound, image acquisitions with all these modalities were performed by using standard clinical protocols. Potential use of this phantom for stent deployment was also tested. A rheometer allowed defining hyperelastic and viscoelastic properties of phantom materials. Results: MR imaging measurements of SNR and CNR values on T1 and T2-weighted sequences and MR angiography indicated reasonable agreement with published values of AAA thrombus and abdominal components in vivo. X-ray absorption also lay within normal ranges of AAA patients and was representative of findings observed on CTA, fluoroscopy, and DSA. Ultrasound propagation speeds for developed materials were also in

  2. Interaction of renal failure and dyslipidaemia in the development of calcific aortic valve disease in rats.

    Science.gov (United States)

    Gillis, Kris; Roosens, Bram; Bala, Gezim; Remory, Isabel; Hernot, Sophie; Delvenne, Philippe; Mestrez, Fabienne; Droogmans, Steven; Cosyns, Bernard

    2017-10-01

    Calcific aortic valve disease (CAVD) is currently the most common heart valve disease worldwide and is known to be an active process. Both renal failure and dyslipidaemia are considered to be promoting factors for the development of valvular calcifications. The aim of this study is to prospectively evaluate the respective contribution and interaction of renal failure and dyslipidaemia on CAVD in a rat model, using echocardiography and compared with histology. Sixty-eight male Wistar rats were prospectively divided in eight groups, each fed a different diet to induce renal failure alone and combined with hyperlipidaemia or hypercholesterolemia. CAVD was detected and quantified by calibrated integrated backscatter of ultrasound (cIB) and compared with the histological calcium score. The study follow-up was 20 weeks. At the end of the study, the cIB value and the calcium score of the aortic valve were significantly increased in the group with isolated renal failure but not with dyslipidaemia. The combination of renal failure with high cholesterol or high-fat diet did not significantly increase calcifications further. Renal failure alone does induce aortic valve calcifications in a rat model of CAVD, whereas dyslipidaemia alone does not. The combination of renal failure with dyslipidaemia does not increase calcification further. These findings suggest that a combination of atherosclerotic and calcifying factors is not required to induce aortic valve calcifications in this model.

  3. Comparison of the effects of levocetirizine and losartan on diabetic nephropathy and vascular dysfunction in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Anbar, Hanan S; Shehatou, George S G; Suddek, Ghada M; Gameil, Nariman M

    2016-06-05

    This work was designed to investigate the effects of levocetirizine, a histamine H1 receptor antagonist, on diabetes-induced nephropathy and vascular disorder, in comparison to an angiotensin II receptor antagonist, losartan. Diabetes was induced in male Sprague Dawley rats by a single intraperitoneal injection of streptozotocin (50mg/kg). Diabetic rats were divided into three groups; diabetic, diabetic-levocetirizine (0.5mg/kg/day) and diabetic-losartan (25mg/kg/day). Treatments were started two weeks following diabetes induction and continued for additional eight weeks. At the end of the experiment, urine was collected and serum was separated for biochemical measurements. Tissue homogenates of kidney and aorta were prepared for measuring oxidative stress, nitric oxide (NO), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Moreover, histological analyses were conducted and aortic vascular reactivity was investigated. Levocetirizine improved renal function in diabetic rats (evidenced by mitigation of diabetes-induced changes in kidney to body weight ratio, serum albumin, urinary proteins and creatinine clearance). Moreover, levocetirizine attenuated the elevated renal levels of TNF-α and TGF-β1, ameliorated renal oxidative stress and restored NO bioavailability in diabetic kidney. These effects were comparable to or surpassed those produced by losartan. Moreover, levocetirizine, similar to losartan, reduced the enhanced responsiveness of diabetic aorta to phenylephrine. Histological evaluation of renal and aortic tissues further confirmed the beneficial effects of levocetirizine on diabetic nephropathy and revealed a greater attenuation of diabetes-induced vascular hypertrophy by levocetirizine than by losartan. In conclusion, levocetirizine may offer comparable renoprotective effect to, and possibly superior vasculoprotective effects than, losartan in streptozotocin-diabetic rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Garlic and Onion Attenuates Vascular Inflammation and Oxidative Stress in Fructose-Fed Rats

    Directory of Open Access Journals (Sweden)

    Marcela Alejandra Vazquez-Prieto

    2011-01-01

    Full Text Available This study evaluates the antioxidant and the anti-inflammatory properties of garlic (G and onion (O in fructose-fed rats (FFR. Thirty-day-old male Wistar rats were assigned to control (C, F (10% fructose in drinking water, F+T (tempol 1 mM as control antioxidant, F+G, and F+O. Aqueous G and O extracts were administered orally in doses of 150 and 400 mg/kg/d respectively, and along with tempol, were given during the last 8 weeks of a 14-week period. At the end of the study, FFR had developed insulin resistance, aortic NADPH oxidase activity, increased SBP, plasma TBARS and vascular cell adhesion molecule-1 (VCAM-1 expression in mesenteric arteries, and a decrease in heart endothelial nitric oxide synthase (eNOS. Garlic and onion administration to F rats reduced oxidative stress, increased eNOS activity, and also attenuated VCAM-1 expression. These results provide new evidence showing the anti-inflammatory and antioxidant effect of these vegetables.

  5. Changes of low back pain after vascular reconstruction for abdominal aortic aneurysm and high aortic occlusion: a retrospective study.

    Science.gov (United States)

    Takeyachi, Yoshiaki; Yabuki, Shoji; Arai, Itaru; Midorikawa, Hirofumi; Hoshino, Shunichi; Chiba, Katsumi; Kikuchi, Shinichi

    2006-08-01

    The purpose of the present study is to clarify the influence of acute and chronic interruption of blood flow from lumbar arteries as well as the influence of vascular reconstruction on low back pain, back muscles, and lumbar discs. Subjects were 34 patients with AAA in whom vascular reconstruction was performed. A second group was comprised of 9 patients with HAO. The presence of low back pain before surgery and at follow-up examination was retrospectively examined in the AAA group and the HAO group to investigate postoperative changes. The CSA and degeneration of the multifidus muscle and the lumbar discs on magnetic resonance imaging were assessed in the AAA group and control group. Low back pain, significant atrophy, or degeneration of the multifidus muscle or degeneration of the lumbar disc did not newly develop after surgery in the AAA group. These results indicated that acute interruption of lumbar arteries did not induce the development or deterioration of low back pain and organic changes in the back muscles or lumbar discs. The frequency of low back pain before surgery was significantly higher in the HAO group than that in the AAA group. However, the frequency of low back pain after surgery did not differ significantly between the 2 groups because low back pain in the HAO group was improved after surgery. The finding that low back pain was improved by merely performing treatment for the vascular system might provide support for the presence of vascular backache.

  6. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  7. 1,25-Dihydroxyvitamin D3 but not cinacalcet HCl (Sensipar/Mimpara) treatment mediates aortic calcification in a rat model of secondary hyperparathyroidism.

    Science.gov (United States)

    Henley, Charles; Colloton, Matt; Cattley, Russell C; Shatzen, Edward; Towler, Dwight A; Lacey, David; Martin, David

    2005-07-01

    Calcitriol treatment of secondary hyperparathyroidism (HPT) in chronic kidney disease (CKD) patients can lead to increased serum calcium and phosphorus, which have been associated as risk factors for vascular calcification. Cinacalcet HCl (Sensipar/Mimpara) {(alphaR)-(-)-alpha-methyl-N-[3-[3-(trifluoromethylphenyl)propyl]-1-napthalenemethanamine hydrochloride} lowers serum parathyroid hormone (PTH), calcium, phosphorus and calcium-phosphorous (CaxP) product in stage 5 CKD dialysis patients; however, its effects on vascular calcification are unknown. Cinacalcet HCl (10 or 1 mg/kg, p.o. gavage), 1,25-dihydroxyvitamin D(3) (0.1 microg, s.c, calcitriol) or the combination was administered daily for 26 days in a rat model of secondary HPT [5/6 nephrectomy]. After dosing, aortic calcification was determined using the von Kossa staining method. Serum PTH and blood chemistries were determined on days 0, 26 and 0, 14, 26, respectively, prior to and after dosing. Calcitriol-treated rats had moderate to marked aortic calcification, whereas no significant calcification was observed in vehicle- or cinacalcet HCl-only treated groups. Co-administration of cinacalcet HCl with calcitriol did not attenuate the calcitriol-mediated increase in CaxP product or calcitriol-mediated aortic calcification. Both calcitriol and cinacalcet HCl therapy significantly reduced serum PTH levels. Calcitriol significantly elevated serum calcium, serum phosphorous and CaxP product above pretreatment levels, or those seen with vehicle or cinacalcet HCl. Cinacalcet HCl (10 or 1 mg/kg) decreased serum ionized calcium and decreased calcitriol-induced hypercalcaemia. Cinacalcet HCl and calcitriol both effectively reduce PTH, albeit via different mechanisms, but unlike calcitriol, cinacalcet HCl did not produce hypercalcaemia, an increased CaxP product or vascular calcification.

  8. Pioglitazone Attenuates Vascular Fibrosis in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Dengfeng Gao

    2012-01-01

    Full Text Available Objective. We sought to investigate whether the peroxisome proliferator-activated receptor-γ (PPAR-γ ligand pioglitazone can attenuate vascular fibrosis in spontaneously hypertensive rats (SHRs and explore the possible molecular mechanisms. Methods. SHRs (8-week-old males were randomly divided into 3 groups (n=8 each for treatment: pioglitazone (10 mg/kg/day, hydralazine (25 mg/kg/day, or saline. Normal male Wistar Kyoto (WKY rats (n=8 served as normal controls. Twelve weeks later, we evaluated the effect of pioglitazone on vascular fibrosis by Masson’s trichrome and immunohistochemical staining of collagen III and real-time RT-PCR analysis of collagen I, III and fibronectin mRNA.Vascular expression of PPAR-γ and connective tissue growth factor (CTGF and transforming growth factor-β (TGF-β expression were evaluated by immunohistochemical staining, western blot analysis, and real-time RT-PCR. Results. Pioglitazone and hydralazine treatment significantly decreased systolic blood pressure in SHRs. Masson’s trichrome staining for collagen III and real-time RT-PCR analysis of collagen I, III and fibronectin mRNA indicated that pioglitazone significantly inhibited extracellular matrix production in the aorta. Compared with Wistar Kyoto rats, SHRs showed significantly increased vascular CTGF expression. Pioglitazone treatment significantly increased PPAR-γ expression and inhibited CTGF expression but had no effect on TGF-β expression. Conclusions. The results indicate that pioglitazone attenuated vascular fibrosis in SHRs by inhibiting CTGF expression in a TGF-β-independent mechanism.

  9. Activation of K{sup +} channels and Na{sup +}/K{sup +} ATPase prevents aortic endothelial dysfunction in 7-day lead-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Fiorim, Jonaina, E-mail: nanafiorim@hotmail.com [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Ribeiro Júnior, Rogério Faustino, E-mail: faustino43@oi.com.br [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Azevedo, Bruna Fernades, E-mail: brunafernandes.azevedo@gmail.com [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Simões, Maylla Ronacher, E-mail: yllars@hotmail.com [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Padilha, Alessandra Simão, E-mail: ale_spadilha@yahoo.com.br [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Stefanon, Ivanita, E-mail: ivanita@pq.cnpq.br [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil); Alonso, Maria Jesus, E-mail: mariajesus.alonso@urjc.es [Departamento de Ciencias de la Salud III, Universidad Rey Juan Carlos, Alcorcón (Spain); Salaices, Mercedes, E-mail: mercedes.salaices@uam.es [Departamento de Farmacología, Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPaz) (Spain); Vassallo, Dalton Valentim, E-mail: daltonv2@terra.com.br [Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES (Brazil)

    2012-07-01

    Seven day exposure to a low concentration of lead acetate increases nitric oxide bioavailability suggesting a putative role of K{sup +} channels affecting vascular reactivity. This could be an adaptive mechanism at the initial stages of toxicity from lead exposure due to oxidative stress. We evaluated whether lead alters the participation of K{sup +} channels and Na{sup +}/K{sup +}-ATPase (NKA) on vascular function. Wistar rats were treated with lead (1st dose 4 μg/100 g, subsequent doses 0.05 μg/100 g, im, 7 days) or vehicle. Lead treatment reduced the contractile response of aortic rings to phenylephrine (PHE) without changing the vasodilator response to acetylcholine (ACh) or sodium nitroprusside (SNP). Furthermore, this treatment increased basal O{sub 2}{sup −} production, and apocynin (0.3 μM), superoxide dismutase (150 U/mL) and catalase (1000 U/mL) reduced the response to PHE only in the treated group. Lead also increased aortic functional NKA activity evaluated by K{sup +}-induced relaxation curves. Ouabain (100 μM) plus L-NAME (100 μM), aminoguanidine (50 μM) or tetraethylammonium (TEA, 2 mM) reduced the K{sup +}-induced relaxation only in lead-treated rats. When aortic rings were precontracted with KCl (60 mM/L) or preincubated with TEA (2 mM), 4-aminopyridine (4-AP, 5 mM), iberiotoxin (IbTX, 30 nM), apamin (0.5 μM) or charybdotoxin (0.1 μM), the ACh-induced relaxation was more reduced in the lead-treated rats. Additionally, 4-AP and IbTX reduced the relaxation elicited by SNP more in the lead-treated rats. Results suggest that lead treatment promoted NKA and K{sup +} channels activation and these effects might contribute to the preservation of aortic endothelial function against oxidative stress. -- Highlights: ► Increased free radicals production ► Increased Na{sup +}/K{sup +} ATPase activity ► Promotes activation of the K{sup +} channels and reduced vascular reactivity ► These effects preserve endothelial function against oxidative

  10. Generation and Characterization of Vascular Smooth Muscle Cell Lines Derived from a Patient with a Bicuspid Aortic Valve

    Directory of Open Access Journals (Sweden)

    Pamela Lazar-Karsten

    2016-04-01

    Full Text Available Thoracic aortic dilation is the most common malformation of the proximal aorta and is responsible for 1%–2% of all deaths in industrialized countries. In approximately 50% of patients with a bicuspid aortic valve (BAV, dilation of any or all segments of the aorta occurs. BAV patients with aortic dilation show an increased incidence of cultured vascular smooth muscle cell (VSMC loss. In this study, VSMC, isolated from the ascending aorta of BAV, was treated with Simian virus 40 to generate a BAV-originated VSMC cell line. To exclude any genomic DNA or cross-contamination, highly polymorphic short tandem repeats of the cells were profiled. The cells were then characterized using flow cytometry and karyotyping. The WG-59 cell line created is the first reported VSMC cell line isolated from a BAV patient. Using an RT2 Profiler PCR Array, genes within the TGFβ/BMP family that are dependent on losartan treatment were identified. Endoglin was found to be among the regulated genes and was downregulated in WG-59 cells following treatment with different losartan concentrations, when compared to untreated WG-59 cells.

  11. In Vivo Remodeling of Fibroblast-Derived Vascular Scaffolds Implanted for 6 Months in Rats

    Directory of Open Access Journals (Sweden)

    Maxime Y. Tondreau

    2016-01-01

    Full Text Available There is a clinical need for tissue-engineered small-diameter (<6 mm vascular grafts since clinical applications are halted by the limited suitability of autologous or synthetic grafts. This study uses the self-assembly approach to produce a fibroblast-derived decellularized vascular scaffold (FDVS that can be available off-the-shelf. Briefly, extracellular matrix scaffolds were produced using human dermal fibroblasts sheets rolled around a mandrel, maintained in culture to allow for the formation of cohesive and three-dimensional tubular constructs, and decellularized by immersion in deionized water. The FDVSs were implanted as an aortic interpositional graft in six Sprague-Dawley rats for 6 months. Five out of the six implants were still patent 6 months after the surgery. Histological analysis showed the infiltration of cells on both abluminal and luminal sides, and immunofluorescence analysis suggested the formation of neomedia comprised of smooth muscle cells and lined underneath with an endothelium. Furthermore, to verify the feasibility of producing tissue-engineered blood vessels of clinically relevant length and diameter, scaffolds with a 4.6 mm inner diameter and 17 cm in length were fabricated with success and stored for an extended period of time, while maintaining suitable properties following the storage period. This novel demonstration of the potential of the FDVS could accelerate the clinical availability of tissue-engineered blood vessels and warrants further preclinical studies.

  12. Candesartan ameliorates arsenic-induced hypertensive vascular remodeling by regularizing angiotensin II and TGF-beta signaling in rats.

    Science.gov (United States)

    Khuman, Maibam Wanta; Harikumar, Sankaran Kutty; Sadam, Abdul; Kesavan, Manickam; Susanth, Vattaparambil Sukumaran; Parida, Subhashree; Singh, Karam Pal; Sarkar, Souvendra Nath

    2016-12-30

    Arsenic exposure can cause several cardiovascular diseases, including hypertension, atherosclerosis and microvascular disease. Earlier, we reported that arsenic-mediated enhancement of angiotensin II (AngII) signaling can impair vascular physiology. Here, we investigated whether the AT1 receptor (AT1R) blocker candesartan can ameliorate the arsenic-induced hypertensive vascular remodeling in rats and whether the amelioration could relate to attenuation in vascular AngII and TGF-β signaling. Rats were exposed to sodium arsenite (50ppm) through drinking water for 90 consecutive days. Candesartan (1mg/kg bw, orally) was administered once daily during the last 30days of arsenic exposure. Non-invasive blood pressure was recorded weekly in conscious rats, while AngII-induced change in mean arterial pressure in anaesthetized rats was measured by invasive method on the 91st day. On this day, blood was collected from other animals for measuring AngII level. Western blot of AT1, AT2 and TβRII receptors; ELISA of PTK, RasGAP, ERK-1/2, TGF-β and CTGF; immunohistochemistry of phosphorylated Smad3, Smad4 and collagen III, hydroxyproline/total collagen estimation, collagen deposition by Masson's trichrome staining and histomorphometry were carried out in thoracic aorta. Arsenic increased non-invasive systolic, diastolic and mean arterial pressure. Further, AngII caused concentration-dependent incremental change in mean arterial pressure in the arsenic-exposed rats. Arsenic upregulated AT1 and TβRII receptor proteins; elevated the levels of PTK, ERK-1/2, TGF-β and CTGF, decreased RasGAP level and augmented the immunoreactivities of Smad3, Smad4 and collagen III. Arsenic also increased hydroxyproline/total collagen level, proliferation of collagen fibres and thickness of aortic wall and collagenous adventitia. Candesartan normalized blood pressure, regularized receptor expressions, MAP kinase and TGF-β signaling, restored collagen deposition and regressed aortic thickness

  13. Impact of routine crossover balloon occlusion technique on access-related vascular complications following transfemoral transcatheter aortic valve replacement.

    Science.gov (United States)

    Zaman, Sarah; Gooley, Robert; Cheng, Victoria; McCormick, Liam; Meredith, Ian T

    2016-08-01

    To determine the impact of incorporating routine crossover balloon occlusion technique (CBOT) for vascular access closure following transcatheter aortic valve replacement (TAVR) on major access-site-related complications. Vascular complications are associated with increased mortality following TAVR. The CBOT involves passage of a balloon catheter from the contralateral femoral artery to enable controlled closure of large-sheath access-sites. Consecutive patients who underwent transfemoral TAVR as part of three clinical trials were prospectively recruited. Patients who had routine CBOT (CBOT group, n = 55) were compared to preceding patients who did not undergo CBOT (control group, n = 43). The primary endpoint was 30-day occurrence of access-site-related Valve Academic Research Consortium (VARC)-2 defined major vascular and/or bleeding complications. CBOT was successfully performed in 96% with 2% occurrence of a minor CBOT-related complication. At 30-days access-site-related major vascular and/or bleeding occurred in 5.5% and 18.6% of the CBOT and control group, respectively (P = 0.042). This consisted of VARC-2 major vascular events in 3.6% and 16.3% (P = 0.036) and VARC-2 major/life-threatening bleeding events in 5.5% and 14.0% (P = 0.137) of the CBOT and control group, respectively. Transfusion of ≥2 units of packed red blood cells were required in 10.9% and 30.2% of the CBOT and control group, respectively (P = 0.016). There was no significant difference in contrast load, procedure time, and kidney injury between the two groups. Routine CBOT for TAVR access-site closure has a high success rate and is associated with a significant reduction in VARC-2 major vascular and bleeding complications compared to TAVR performed without CBOT. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Binding, internalization, and degradation of atrial natriuretic peptide in cultured vascular smooth muscle cells of rat

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Y.; Takata, S.; Tomita, M.; Takaichi, S.

    1985-11-15

    Binding, internalization, and degradation of /sup 125/I-labeled-rat atrial natriuretic peptide (rANP) were studied in cultured rat aortic vascular smooth muscle cells (VSMC). At 37 degrees C, /sup 125/I-labeled-rANP rapidly bound to VSMCs, but the cell-bound radioactivity rapidly decreased upon subsequent incubation, while the binding was slow at 4 degrees C, reaching to an apparent equilibrium after 6 hrs. The cell-bound /sup 125/I-labeled-rANP at 37 degrees C is rapidly dissociated from VSMC (t 1/2: approximately 40 min) with the appearance of degradaded product(s) of radioligand in the medium, whereas the degradation was minimal at 4 degrees C. This degradative process was blocked by inhibitors of metabolic energy production (azide, dinitrophenol), inhibitors of lysosomal cathepsins (leupeptin, pepstatin), and lysosomotropic agents (NH/sub 4/Cl, chloroquine, lidocaine, methylamine, dansylcadaverine), but not by inhibitors of serine or thiol proteases. /sup 125/I-labeled-rANP initially bound to the cell-surface was rapidly internalized, and delivered to lysosomal structures, which was confirmed by autoradiographic studies. These data indicate that rANP, after binding to the cell-surface receptors, is rapidly internalized into the cells through receptor-mediated endocytosis, and subsequently degradaded by lysosomal hydrolases.

  15. Prevention of abdominal aortic aneurysm progression by oral administration of green tea polyphenol in a rat model.

    Science.gov (United States)

    Setozaki, Shuji; Minakata, Kenji; Masumoto, Hidetoshi; Hirao, Shingo; Yamazaki, Kazuhiro; Kuwahara, Koichiro; Ikeda, Tadashi; Sakata, Ryuzo

    2017-06-01

    Inflammation-mediated elastin destruction in the aortic medial layer is related to progression of abdominal aortic aneurysm (AAA). Epigallocatechin-3-gallate (EGCG), a major component of green tea polyphenols, reportedly increases elastin synthesis in vitro and may possess anti-inflammatory effects. We used a rat model to investigate whether EGCG could prevent AAA progression. AAA was induced with administration of intraluminal elastase and extraluminal CaCl2 in male rats. Rats were randomly divided into a control group (n = 30) and an EGCG group (n = 30). In the EGCG group, an EGCG solution (20 mg/d) was administered orally to each rat from 2 weeks before AAA induction and continued 4 weeks beyond induction. The abdominal aortic diameter was significantly smaller in the EGCG group than in the control group on day 28 (2.9 ± 0.2 vs 2.3 ± 0.1 mm; P oxidase were significantly higher in the EGCG group immediately before AAA induction, indicating promoted elastoregeneration by EGCG administration (tropoelastin: 0.59 ± 0.36 control vs 1.24 ± 0.36 EGCG [P oxidase: 0.77 ± 0.45 control vs 1.34 ± 0.4 EGCG [P < .05]) (fold increase). Gene expression levels of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, were significantly downregulated in the EGCG group (1.82 ± 0.71 vs 0.97 ± 0.59 [P < .05] and 3.91 ± 3.24 vs 0.89 ± 0.59 [P < .05], respectively). On day 7, gene expression levels and gelatinolytic activity of matrix metalloproteinase 9 were significantly lower in the EGCG group (1.41 ± 0.86 vs 0.51 ± 0.42 [P < .05] and 1.00 ± 0.17 vs 0.29 ± 0.12 [P < .0001], respectively), whereas gene expression levels of tissue inhibitors of metalloproteinase-1 were significantly higher in the EGCG group (0.96 ± 0.11 vs 1.14 ± 0.09; P < .05). EGCG attenuated AAA progression in a rat model by preserving the aortic thickness and elastin content of the medial layer through regeneration of elastin, as mediated by

  16. Reduced L-Carnitine Transport in Aortic Endothelial Cells from Spontaneously Hypertensive Rats

    Science.gov (United States)

    Salsoso, Rocío; Guzmán-Gutiérrez, Enrique; Arroyo, Pablo; Salomón, Carlos; Zambrano, Sonia; Ruiz-Armenta, María Victoria; Blanca, Antonio Jesús; Pardo, Fabián; Leiva, Andrea; Mate, Alfonso; Sobrevia, Luis; Vázquez, Carmen María

    2014-01-01

    Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na+-independent) and 2 (Octn2, Na+-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5–8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1–100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na+-dependent (Na+dep) compared with Na+-independent (Na+indep) transport components. Saturable L-carnitine transport kinetics show maximal velocity (Vmax), without changes in apparent Km for Na+indep transport in SHR compared with WKY rats. Total and Na+dep component of transport were increased, but Na+indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na+indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results suggest that reduced L

  17. Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats.

    Science.gov (United States)

    Salsoso, Rocío; Guzmán-Gutiérrez, Enrique; Arroyo, Pablo; Salomón, Carlos; Zambrano, Sonia; Ruiz-Armenta, María Victoria; Blanca, Antonio Jesús; Pardo, Fabián; Leiva, Andrea; Mate, Alfonso; Sobrevia, Luis; Vázquez, Carmen María

    2014-01-01

    Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na(+)-independent) and 2 (Octn2, Na(+)-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5-8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1-100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na(+)-dependent (Na(+) dep ) compared with Na(+)-independent (Na(+) indep ) transport components. Saturable L-carnitine transport kinetics show maximal velocity (V max), without changes in apparent K m for Na(+) indep transport in SHR compared with WKY rats. Total and Na(+) dep component of transport were increased, but Na(+) indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na(+) indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results

  18. Zoledronate upregulates MMP-9 and -13 in rat vascular smooth muscle cells by inducing oxidative stress

    Directory of Open Access Journals (Sweden)

    Arun MZ

    2016-04-01

    Full Text Available Mehmet Zuhuri Arun,1 Buket Reel,1 Graciela B Sala-Newby,2 Mark Bond,2 Aikaterini Tsaousi,2 Perry Maskell,2 Andrew C Newby21Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey; 2Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol, UK Background: Bisphosphonates, including zoledronate, target osteoclasts and are widely used in the treatment of osteoporosis and other bone resorption diseases, despite side effects that include damaging the stomach epithelium. Beneficial and adverse effects on other organ systems, including the cardiovascular system, have also been described and could impact on the use of bisphosphonates as therapeutic agents. Vascular smooth muscle cells (VSMCs are major constituents of the normal vascular wall and have a key role in intimal thickening and atherosclerosis, in part by secreting MMPs that remodel the extracellular matrix and cleave cell surface proteins or secreted mediators. In this study, we investigated the effects of zoledronate on MMP expression.Methods: Rat VSMCs were stimulated by PDGF (50 ng/mL plus TNF-α (10 ng/mL or left unstimulated for a further 24 hours in serum-free medium. In other series of experiments, cells were pre-treated either with SC-514 (50 µM or with apocynin (20 nM for 2 hours, then zoledronate (100 µM was added into 2% fetal calf serum containing medium for 24 hours.Results and discussion: Using isolated rat VSMCs in culture, zoledronate (100 µM increased MMP-9 and -13 mRNA expressions but inhibited MMP-2 expression. MMP-9 and MMP-13 up-regulation was shown to depend on the NF-κB pathway; and this was activated by zoledronate. Furthermore, zoledronate elevated the levels of reactive oxygen species detected by either dichlorofluorescein in isolated VSMCs or lucigenin enhanced chemiluminescence in rat aortic rings in vitro. Apocynin, an inhibitor of NADPH oxidase, reversed NF-κB activation and MMP-9 and MMP-13 up-regulation by

  19. Vascular activation of K+ channels and Na+-K+ ATPase activity of estrogen-deficient female rats.

    Science.gov (United States)

    Ribeiro Junior, Rogério Faustino; Fiorim, Jonaina; Marques, Vinicius Bermond; de Sousa Ronconi, Karoline; Botelho, Tatiani; Grando, Marcella D; Bendhack, Lusiane M; Vassallo, Dalton Valentim; Stefanon, Ivanita

    2017-12-01

    The goal of the present study was to evaluate vascular potassium channels and Na+-K+-ATPase activity in estrogen deficient female rats. Female rats that underwent ovariectomy were assigned to receive daily treatment with placebo (OVX) or estrogen replacement (OVX+E2, 1mg/kg, once a week, i.m.). Aortic rings were used to examine the involvement of K+ channels and Na+-K+-ATPase in vascular reactivity. Acetylcholine (ACh)-induced relaxation was analyzed in the presence of L-NAME (100μM) and K+ channels blockers: tetraethylammonium (TEA, 5mM), 4-aminopyridine (4-AP, 5mM), iberiotoxin (IbTX, 30nM), apamin (0.5mM), charybdotoxin (ChTX, 0.1mM) and iberiotoxin plus apamin. When aortic rings were pre-contracted with KCl (60mM) or pre-incubated with TEA (5mM), 4-aminopyridine (4-AP, 5mM) and iberiotoxin (IbTX, 30nM) plus apamin (0.5μM), the ACh-induced relaxation was less effective in the ovariectomized group. Additionally, 4-AP and IbTX decreased the relaxation by sodium nitroprusside in all groups but this reduction was greater in the ovariectomized group. Estrogen deficiency also increased aortic functional Na+-K+ ATPase activity evaluated by K+-induced relaxation. L-NAME or endothelium removal were not able to block the increase in aortic functional Na+-K+ ATPase activity, however, TEA (5mM) restored this increase to the control level. We also found that estrogen deficiency increased superoxide anion production and reduced nitric oxide release in aortic ring from ovariectomized animals. In summary, our results emphasize that the process underlying ACh-induced relaxation is preserved in ovariectomized animals due to the activation of K+ channels and increased Na+-K+ ATPase activity. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Unequal pressure distribution along the jaws of currently available vascular clamps: do we need a new aortic clamp?

    Science.gov (United States)

    Rylski, Bartosz; Schmid, Claudius; Beyersdorf, Friedhelm; Kari, Fabian Alexander; Kondov, Stoyan; Lutz, Lisa; Werner, Martin; Czerny, Martin; Siepe, Matthias

    2016-06-01

    The pressure along vascular clamp jaws may be unequally distributed, with greater pressure near the clamp hinge than at its top. Such unequal pressure distribution may cause aortic injury, especially in large aortas. We evaluated pressure distribution along different currently availably clamp jaws. Seven descending thoracic aortas from pigs (diameter 2.0-3.0 cm) were plainly dissected and all side arteries closed. Aortas were filled up with water and cross-clamped. The pressure inside the aorta was raised to 100 mmHg and the aorta was clamped so tightly that no water exited from the distal aortic end. Each aorta was clamped seven times at different sites with the following clamps: DeBakey, Satinsky, femoral, iliac, Chitwood, angled handle Fogarty and straight handle Fogarty. The pressure along the clamp jaws was measured with a pressure-detecting film placed between the clamp jaws and aorta. The collagen-fibre disorganization was examined in haemotoxylin-eosin- and Elastica van Gieson-stained tissue samples. The DeBakey clamp revealed the lowest maximum pressure along the clamp jaws after complete aortic occlusion (1.43 ± 0.49 MPa), whereas the Chitwood clamp's pressure was the highest (3.26 ± 1.93 MPa, P clamp displayed the lowest difference between maximum pressures across the jaws (33%), with the greatest difference measured in the iliac (72%) and Chitwood (66%) clamps. The highest collagen-fibre disorganization score was observed in the proximal-to-the-clamp-hinge quartile after clamping with the angled handle Fogarty (2.8 ± 0.4), straight handle Fogarty (2.3 ± 0.8) and Chitwood (2.3 ± 0.5) clamps. The pressure along clamp jaws is unequally distributed in all the currently available vascular clamps. The Chitwood clamp is associated with the highest maximum pressure during complete aortic occlusion and with the most unequal pressure distribution along the jaws. © The Author 2015. Published by Oxford University Press on behalf of the European Association

  1. Effects of Kaempferia parviflora rhizomes dichloromethane extract on vascular functions in middle-aged male rat.

    Science.gov (United States)

    Yorsin, Somruedee; Kanokwiroon, Kanyanatt; Radenahmad, Nisaudah; Jansakul, Chaweewan

    2014-10-28

    In Thai traditional medicine, rhizomes of Kaempferia parviflora (KP) have been used for treating hypertension and for the promotion of longevity with good health and well being. Ageing is one of the most important risk factors for development of cardiovascular disease. To investigate whether a 6 weeks oral administration of a dichloromethane extract of fresh rhizomes of Kaempferia parviflora (KPD) had any effects on vascular functions, on the accumulation of lipid, as well as on any signs of gross organ toxicity in middle-aged rats. Fresh rhizomes of Kaempferia parviflora were first macerated twice with 95% ethanol to remove the dark color before extracting three times with 100% dichloromethane. The dichloromethane extract was evaporated under reduced pressure to obtain the dried Kaempferia parviflora dichloromethane extract (KPD). The rats were orally administered with the KPD at a dosage of 100mg/kg body weight, or with the same volume of the vehicle (tween 80, 0.2g: carboxy-methylcellulose sodium, 0.2g: distilled water 10 ml) once or twice a day for 6 weeks. Vascular functions were studied on isolated thoracic aorta and the mesenteric artery. The vascular eNOS enzyme was measured by Western blot analysis. Blood chemistry was measured by enzymatic methods. Liver cell lipid accumulation was measured using oil red O staining. A 6 weeks treatment of KPD once a day had no significant effects on any of the studied parameters. When the KPD was given twice a day, the contractile responses to phenylephrine of the thoracic aorta and mesenteric artery were lower than the vehicle control group, and this effect was abolished by N(G)-nitro-l-arginine or by removal of the vascular endothelium. Vasorelaxation to acetylcholine, but not to glyceryl trinitrate, by the thoracic aortic and mesenteric ring precontracted with phenylephrine was higher from the KPD treated rats than those from the vehicle control groups. Western blot analysis showed a higher quantity of thoracic- and

  2. Vascular complications with transcatheter aortic valve implantation using the 18 Fr Medtronic CoreValve System®: The Rotterdam experience

    NARCIS (Netherlands)

    N.M. van Mieghem (Nicolas); R-J.M. Nuis (Rutger-Jan); N. Piazza (Nicolo); A. Tzikas (Apostolos); J.M.R. Ligthart (Jürgen); C.J. Schultz (Carl); P.P.T. de Jaegere (Peter); P.W.J.C. Serruys (Patrick)

    2010-01-01

    textabstractAims: Transcatheter aortic valve implantation (TAVI) requires large bore catheters. Access site complications, therefore, can be a concern. The aim of this study is to present the 30-day incidence of major and minor vascular complications in patients treated with the third generation 18

  3. Vascular damage after fractionated whole-brain irradiation in rats.

    Science.gov (United States)

    Brown, William R; Thore, Clara R; Moody, Dixon M; Robbins, Michael E; Wheeler, Kenneth T

    2005-11-01

    Whole-brain irradiation of animals and humans has been reported to lead to late delayed structural (vascular damage, demyelination, white matter necrosis) and functional (cognitive impairment) alterations. However, most of the experimental data on late delayed radiation-induced brain injury have been generated with large single doses or short fractionation schemes that may provide a less accurate indication of the events that occur after clinical whole-brain radiotherapy. The pilot study reported here investigates cerebral vascular pathology in male Fischer 344 rats after whole-brain irradiation with a fractionated total dose of 137Cs gamma rays that is expected to be biologically similar to that given to brain tumor patients. The brains of young adult rats (4 months old) were irradiated with a total dose of 40 Gy, given as eight 5-Gy fractions twice per week for 4 weeks. Brain capillary and arteriole pathology was studied using an alkaline phosphatase enzyme histochemistry method; vessel density and length were quantified using a stereology method with computerized image processing and analysis. Vessel density and length were unchanged 24 h after the last dose, but at 10 weeks postirradiation, both were substantially decreased. After 20 weeks, the rate of decline in the vessel density and length in irradiated rats was similar to that in unirradiated age-matched controls. No gross gliosis or demyelination was observed 12 months postirradiation using conventional histopathology techniques. We suggest that the early (10-week) and persistent vascular damage that occurs after a prolonged whole-brain irradiation fractionation scheme may play an important role in the development of late delayed radiation-induced brain injury.

  4. Evaluation of intra-aortic CT angiography performances for the visualisation of spinal vascular malformations' angioarchitecture

    Energy Technology Data Exchange (ETDEWEB)

    Clarencon, Frederic; Gabrieli, Joseph; Chiras, Jacques [Pitie-Salpetriere Hospital, Department of Interventional Neuroradiology, Paris (France); Paris VI University, Pierre et Marie Curie University, Paris (France); Di Maria, Federico; Sourour, Nader-Antoine; Shotar, Eimad; Cormier, Evelyne; Fahed, Robert [Pitie-Salpetriere Hospital, Department of Interventional Neuroradiology, Paris (France); Nouet, Aurelien [Pitie-Salpetriere Hospital, Department of Neurosurgery, Paris (France); Cornu, Philippe [Paris VI University, Pierre et Marie Curie University, Paris (France); Pitie-Salpetriere Hospital, Department of Neurosurgery, Paris (France)

    2016-10-15

    To evaluate the performances of the CT-angiography by direct intra-aortic contrast media injection (IA-CTA) for spinal vascular malformations (SVMs)' imaging. Thirteen patients (8 males, 5 females, mean age: 56 y) with suspected SVM underwent IA-CTAs by direct intra-aortic iodinated contrast media injection (5 cc/s; 100 cc) via an arterial femoral or humeral access. Two independent observers evaluated the angioarchitecture of the SVMs and the visualisation of both the Adamkiewicz artery and the anterior spinal artery. Then a consensus was obtained between the 2 reviewers; the results of the IA-CTA were finally compared with those of the full spinal DSA evaluated in consensus. The IA-CTA was feasible in all cases and depicted the SVM in all except one case (92 %). Interrater agreement was good for the location of the SVMs' level. Intermodality (IA-CTA/DSA) agreement was excellent for the level and side of the shunt point, as well as for the SVM subtype evaluation. In 77 % of the cases, the Adamkiewicz artery was satisfactorily seen at the same time on IA-CTA. IA-CTA is a new technique that seems helpful to reach a better understanding of SMVs and may help to tailor more precisely their treatment. (orig.)

  5. Aortic Graft Infection: Graphene Shows the Way to an Infection-Resistant Vascular Graft

    Directory of Open Access Journals (Sweden)

    Nikolaos Patelis

    2017-05-01

    Full Text Available Aortic graft infection is a potentially lethal complication of open and endovascular repair of aortic aneurysms. Graphene is the only existing two-dimensional material, and its unique structure gives graphene and its derivatives a plethora of original characteristics. Among other characteristics, graphene demonstrates bacteriostatic and bactericidal effects that could potentially resolve the problem of graft infection in the future. Data already exist in literature supporting this antibacterial effect of graphene oxide and reduced graphene oxide. Combining these materials with other substances enhances the antibacterial effect. Additionally, it looks feasible to expect antibiotic-delivering graphene-based graft materials in the future. Based on already published data, we could conclude that regarding graphene and its derivatives, the blessing of bactericidal effect comes with the curse of human cells toxicity. Therefore, it is important to find a fine balance between the desired antibacterial and the adverse cytotoxic effect before graphene is used in graft materials for humans.

  6. Effect of Curcumin on Angiogenesis in Aortic Ring Model of the Wistar Rat

    Directory of Open Access Journals (Sweden)

    J Baharara

    2014-08-01

    Full Text Available Introduction: Tumeric is a plant with both food and medical properties by which Curcumin is derived from. It has various pharmacological effects. Angiogenesis, a dynamic process of endothelial cells proliferation in order to develop new blood vessels from the previous ones, affects a wide range of physiological and pathological processes such as tumor growth and metastasis. In this study, anti angiogenic effects of Cucumin were investigated in aortic ring of Wistar rats. Methods: In this experimental study, Aortic ring was cut up in to 1 mm pieces and cultured in collagen matrix. After three days, sprouting angiogenesis were observed, and then aortic rings were treated with Curcumin at concentration of 25, 50 and 100 µg/ml. Effects of treatment in all cases were photographed and then investigated by invert microscope. Lengths of vessels were measured by Image J software. Moreover, the study data were analyzed using SPSS in significant level of P0.05.In fact, average length and number of blood vessels in experimental group 1 demonstrated no significant difference compared with control group, though in the experimental group 2 (79.45±3.2mm, (12±1.3 and 3 (38.93±1.1mm, (8±1.1 significant differences were observed (P<0.05(. Conclusion: The results proposed that the Curcumin had dose-dependent inhibitory effects on angiogenesis in rat aortic ring Therefore, it can be introduced as an appropriate candidate in order to study angiogenesis and related diseases.

  7. Rock Tea extract (Jasonia glutinosa) relaxes rat aortic smooth muscle by inhibition of L-type Ca(2+) channels.

    Science.gov (United States)

    Valero, Marta Sofía; Oliván-Viguera, Aida; Garrido, Irene; Langa, Elisa; Berzosa, César; López, Víctor; Gómez-Rincón, Carlota; Murillo, María Divina; Köhler, Ralf

    2015-12-01

    In traditional herbal medicine, Rock Tea (Jasonia glutinosa) is known for its prophylactic and therapeutic value in various disorders including arterial hypertension. However, the mechanism by which Rock Tea exerts blood pressure-lowering actions has not been elucidated yet. Our aim was to demonstrate vasorelaxing effects of Rock Tea extract and to reveal its possible action mechanism. Isometric myography was conducted on high-K+-precontracted rings from rat thoracic aorta and tested extracts at concentrations of 0.5-5 mg/ml. Whole-cell patch-clamp experiments were performed in rat aortic vascular smooth muscle cells (line A7r5) to determine blocking effects on L-type Ca(2+) channels. Rock Tea extract relaxed the aorta contracted by high [K+] concentration dependently with an EC50 of ≈2.4 mg/ml and produced ≈75 % relaxation at the highest concentration tested. The L-type Ca(2+) channel blocker, verapamil (10(-6) M), had similar effects. Rock Tea extract had no effect in nominally Ca(2+)-free high-K(+) buffer but significantly inhibited contractions to re-addition of Ca(2+). Rock Tea extract inhibited the contractions induced by the L-type Ca(2+) channel activator Bay K 8644 (10(-5) M) and by phenylephrine (10(-6) M). Rock Tea extract and Y-27632 (10(-6) M), Rho-kinase inhibitor, had similar effects and the respective effects were not additive. Patch-clamp experiments demonstrated that Rock Tea extract (2.5 mg/ml) virtually abolished L-type Ca(2+) currents in A7r5. We conclude that Rock Tea extract produced vasorelaxation of rat aorta and that this relaxant effect is mediated by inhibition of L-type Ca(2+) channels. Rock Tea extracts may be of phytomedicinal value for prevention and adjuvant treatment of hypertension and other cardiovascular diseases.

  8. Spaceflight Affects Postnatal Development of the Aortic Wall in Rats

    Directory of Open Access Journals (Sweden)

    Shin-ichiro Katsuda

    2014-01-01

    Full Text Available We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam. The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta.

  9. Spaceflight Affects Postnatal Development of the Aortic Wall in Rats

    Science.gov (United States)

    Yamasaki, Masao; Waki, Hidefumi; Miyake, Masao; Nagayama, Tadanori; Miyamoto, Yukako; Wago, Haruyuki; Okouchi, Toshiyasu; Shimizu, Tsuyoshi

    2014-01-01

    We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam). The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta. PMID:25210713

  10. A Single Resistance Exercise Session Improves Aortic Endothelial Function in Hypertensive Rats.

    Science.gov (United States)

    Faria, Thaís de Oliveira; Angeli, Jhuli Keli; Mello, Luiz Guilherme Marchesi; Pinto, Gustavo Costa; Stefanon, Ivanita; Vassallo, Dalton Valentim; Lizardo, Juliana Hott de Fúcio

    2017-03-01

    Physical exercise is an important tool for the improvement of endothelial function. To assess the effects of acute dynamic resistance exercise on the endothelial function of spontaneously hypertensive rats (SHR). Ten minutes after exercise, the aorta was removed to evaluate the expression of endothelial nitric oxide synthase (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS1177) and inducible nitric oxide synthase (iNOS) and to generate concentration-response curves to acetylcholine (ACh) and to phenylephrine (PHE). The PHE protocol was also performed with damaged endothelium and before and after NG-nitro-L-arginine methyl ester (L-NAME) and indomethacin administration. The maximal response (Emax) and the sensitivity (EC50) to these drugs were evaluated. ACh-induced relaxation increased in the aortic rings of exercised (Ex) rats (Emax= -80 ± 4.6%, p controls (Ct) (Emax = -50 ± 6.8%). The Emax to PHE was decreased following exercise conditions (95 ± 7.9%, p control conditions (120 ± 4.2%). This response was abolished after L-NAME administration or endothelial damage. In the presence of indomethacin, the aortic rings' reactivity to PHE was decreased in both groups (EC50= Ex -5.9 ± 0.14 vs. Ct -6.6 ± 0.33 log µM, p session improves endothelial function in hypertensive rats. This response seems to be mediated by increased NO production through eNOS activation.

  11. DPP4 deficiency preserved cardiac function in abdominal aortic banding rats.

    Directory of Open Access Journals (Sweden)

    Hui-Chun Ku

    Full Text Available Dipeptidyl peptidase-4 (DPP4 enzyme inhibition has been reported to increase plasma glucagon-like peptide-1 (GLP-1 level for controlling postprandial glucose concentration. A prominent GLP-1 level in DPP4-deficient rats contributed to the resistance of endotoxemia and myocardial infarction. DPP4 deficiency also increased the capability against H₂O₂-induced stress in cardiomyocyte. However, long term effect of loss DPP4 activity on cardiac performance remained unclear. We used abdominal aortic banding (AAB to induce pressure overload in wild-type and DPP4-deficient rats, and investigated the progression of heart failure. Cardiac histology and function were determined. Blood sample was collected for the plasma biochemical marker measurement. Heart weight to body weight ratio increased 1.2-fold after 6 weeks of AAB surgery. Cardiac function was compensated against pressure overload after 6 weeks of AAB surgery, but progressed to deterioration after 10 weeks of AAB surgery. AAB induced cardiac dysfunction was alleviated in DPP4-deficient rats. DPP4 activity increased significantly in wild-type rats after 10 weeks of AAB surgery, but remained unchanged in DPP4-deficient rats. In contrast, GLP-1 concentration was elevated by AAB after 6 weeks of surgery in DPP4-deficient rats, and remained high after 10 weeks of surgery. Ang II level markedly increased after 6 weeks of AAB surgery, but were less in DPP4-deficient rats. Massive collagen deposits in wild-type rat hearts appeared after 10 weeks of AAB surgery, which were alleviated in DPP4-deficient rats. Long term deficiency of DPP4 activity improved cardiac performance against pressure overload in rat, which may be attributed to a great quantity of GLP-1 accumulation during AAB.

  12. PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway.

    Science.gov (United States)

    Kim, Yun H; Lee, Seung J; Seo, Kyo W; Bae, Jin U; Park, So Y; Kim, Eun K; Bae, Sun S; Kim, Jae H; Kim, Chi D

    2013-10-01

    Platelet-activating factor (PAF), 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, is a potent phospholipid mediator and has been reported to be localized in atherosclerotic plaque. However, its role in the progression of atherosclerosis remains unclear. In the present study, we investigated the role of PAF in the production of matrix metalloproteinase (MMP) in primary vascular smooth muscle cells (VSMCs). When rat aortic primary VSMCs were stimulated with PAF (1 nmol/l), the expressions of MMP-2 mRNA and protein, but not of MMP-9, were significantly increased, and these upregulations were markedly attenuated by inhibiting extracellular signal-regulated kinases (ERKs) using molecular and pharmacological inhibitors, but not by using inhibitors of p38 mitogen-activated protein kinase or c-Jun N-terminal kinase. Likewise, ERK phosphorylation was markedly enhanced in PAF-stimulated VSMCs, and this was attenuated by WEB2086, but not by EGF receptor inhibitor, demonstrating the specificity of PAF receptor (PAFR) in PAF-induced ERK phosphorylation. In immunofluorescence studies, β-arrestin2 in PAF-stimulated VSMCs colocalized with PAFR and phosphorylated ERK (P-ERK). Coimmunoprecipitation results suggest that β-arrestin2-bound PAFRs existed as a complex with P-ERK. In addition, PAF-induced ERK phosphorylation and MMP-2 production were significantly attenuated by β-arrestin2 depletion. Taken together, the study shows that PAF enhances MMP-2 production in VSMCs via a β-arrestin2-dependent ERK signaling pathway.

  13. STIM1/Orai1 contributes to sex differences in vascular responses to calcium in spontaneously hypertensive rats.

    Science.gov (United States)

    Giachini, Fernanda R C; Lima, Victor V; Filgueira, Fernando P; Dorrance, Anne M; Carvalho, Maria Helena C; Fortes, Zuleica B; Webb, R Clinton; Tostes, Rita C

    2012-03-01

    Sex differences in Ca2+-dependent signalling and homoeostasis in the vasculature of hypertensive rats are well characterized. However, sex-related differences in SOCE (store-operated Ca2+ entry) have been minimally investigated. We hypothesized that vascular protection in females, compared with males, reflects decreased Ca2+ mobilization due to diminished activation of Orai1/STIM1 (stromal interaction molecule 1). In addition, we investigated whether ovariectomy in females affects the activation of the Orai1/STIM1 pathway. Endothelium-denuded aortic rings from male and female SHRSP (stroke-prone spontaneously hypertensive rats) and WKY (Wistar-Kyoto) rats and from OVX (ovariectomized) or sham female SHRSP and WKY rats were used to functionally evaluate Ca2+ influx-induced contractions. Compared with females, aorta from male SHRSP displayed: (i) increased contraction during the Ca2+-loading period; (ii) similar transient contraction during Ca2+ release from the intracellular stores; (iii) increased activation of STIM1 and Orai1, as shown by the blockade of STIM1 and Orai1 with neutralizing antibodies, which reversed the sex differences in contraction during the Ca2+-loading period; and (iv) increased expression of STIM1 and Orai1. Additionally, we found that aortas from OVX-SHRSP showed increased contraction during the Ca2+-loading period and increased Orai1 expression, but no changes in the SR (sarcoplasmic reticulum)-buffering capacity or STIM1 expression. These findings suggest that augmented activation of STIM1/Orai1 in aortas from male SHRSP represents a mechanism that contributes to sex-related impaired control of intracellular Ca2+ levels. Furthermore, female sex hormones may negatively modulate the STIM/Orai1 pathway, contributing to vascular protection observed in female rats.

  14. Radiographic assessment of vascular calcification, aortic pulse wave velocity, ankle-brachial index and fibroblast growth factor-23 in chronic hemodialysis patients.

    Science.gov (United States)

    Breznik, Silva; Ekart, Robert; Hren, Martin; Rupreht, Mitja; Balon, Breda Pečovnik

    2013-08-01

    Vascular calcification is a frequent complication of chronic kidney disease and end stage renal disease. In both the general population and patients with end stage renal disease, vascular calcification is related to arterial stiffness and is a predictor of cardiovascular morbidity and mortality. Various diagnostic methods are currently used to assess vascular calcification. There is a preference for simple, reliable methods that can be used in daily practice. Therefore, several imaging and laboratory methods are investigated. Twenty-eight patients with mean age of 62 years on chronic hemodialysis were enrolled in the study. The mean duration of hemodialysis treatment was 70 months (range 3 to 350 months). Vascular calcification was assessed with coronary computed tomography and lateral lumbar, pelvic and hand radiographs. Vascular stiffness was evaluated using aortic pulse wave velocity and ankle-brachial index measurements, and finally serum levels of fibroblast growth factor-23 were followed. A statistically significant correlation was demonstrated between all the following parameters: coronary artery calcification score, aortic pulse wave velocity, abdominal aortic calcification score, simple vascular calcification scores in pelvis and hand. A statistically significant correlation of ankle-brachial index >1.3 to coronary artery calcification score was found. There was no correlation between the previous parameters and fibroblast growth factor-23. The results of our study indicate that simple imaging methods could provide confident vascular damage assessment and therefore potentially guide therapy adjustments. An association between fibroblast growth factor-23 and the other diagnostic modalities in our study was not found. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

  15. Data for the Oxford Abdominal Aortic Aneurysm Study international survey of vascular surgery professionals

    Directory of Open Access Journals (Sweden)

    Regent Lee

    2017-10-01

    This Data-in-Brief article contains a detailed method for the conduct of this survey and additional original data. In this survey, we also provided vascular surgery colleagues with contemporary epidemiologic and surgical outcome data. This was followed by a hypothetical scenario whereby a patient had just been diagnosed with a small (40 mm AAA and a novel biomarker predicted it to be fast growing in the coming years. We assessed the vascular professionals' perception of the patient's preference for management in this scenario, and their willingness to refer patients for a surgical trial that investigates the outcome of early versus late surgery in this setting. The survey then asked the vascular professionals to assume the role of the patient, and provided their own preferences in such a scenario.

  16. Association between the synthetic vascular stent used for abdominal aortic aneurysm and generalized granuloma annulare

    Directory of Open Access Journals (Sweden)

    Han-Chi Tseng

    2015-09-01

    Full Text Available The etiology of granuloma annulare (GA remains unknown, although several eliciting factors have been proposed. We herein present the case of an 81-year-old man who developed generalized erythematous annular plaques 6 months after engraftment of a vascular stent for abdominal aneurysm repair. Based on the diagnosis of generalized GA and the patient's age, we treated him with psoralens plus ultraviolet A therapy. The treatment response was good. This is the first report showing the association between vascular stent and generalized GA.

  17. Genistein prevents hyperglycemia-induced monocyte adhesion to human aortic endothelial cells through preservation of the cAMP signaling pathway and ameliorates vascular inflammation in obese diabetic mice

    National Research Council Canada - National Science Library

    Babu, Pon Velayutham Anandh; Si, Hongwei; Fu, Zhuo; Zhen, Wei; Liu, Dongmin

    2012-01-01

    ...) interaction is the key event in the pathogenesis of atherosclerosis in diabetes. Here, we investigated the effect of isoflavone genistein on hyperglycemia-stimulated vascular inflammation. Human aortic EC (HAEC...

  18. Testosterone reduces vascular relaxation by altering cyclic adenosine monophosphate pathway and potassium channel activation in male Sprague Dawley rats fed a high-salt diet.

    Science.gov (United States)

    Oloyo, Ahmed K; Sofola, Olusoga A; Anigbogu, Chikodi N; Nair, Renuka R; Vijayakumar, Harikrishnan S; Fernandez, Adelaide C

    2013-04-01

    Male gender and high-salt diet are risk factors for hypertension. The effect of chronic exposure to testosterone is an increase in vascular tone but its influence upon responses induced by other vasoactive agents is not clear. We considered the possibility of interactions between testosterone and a high-salt diet in the mechanisms that are involved in the regulation of vascular tone. Therefore, we designed experiments to assess the involvement of the cyclic adenosine monophosphate (cAMP) pathway and potassium channel activation on vascular relaxation elicited by testosterone deficiency that was induced by orchidectomy in Sprague Dawley rats on a normal or high-salt diet. Weanling male rats were randomly divided into eight groups (n = 6 each) that were either orchidectomized or sham operated with or without testosterone replacement (10 mg/kg body weight of Sustanon 250 intramuscularly, Organon, Holland) and were placed on a normal or high-salt (0.3% or 8% NaCl) diet, respectively, for 6 weeks. Arterial blood pressure was determined before and weekly throughout the experiment using the tail-cuff method. Relaxation responses to forskolin and diazoxide were studied in noradrenaline (0.1 µM) precontracted aortic rings. There was an increase in the systolic blood pressure of rats placed on a high-salt diet compared with control or orchidectomized rats. Orchidectomy elicited a reduction in the systolic blood pressure while testosterone replacement restored systolic blood pressure to values seen in intact rats. A high-salt diet reduced the relaxation response to forskolin and diazoxide but not in orchidectomized rats while testosterone replacement re-established the blunted relaxation response to forskolin and diazoxide. Inhibition of potassium channel or adenylyl cyclase activation appears to contribute to the mechanisms by which a high-salt diet increases vascular tone. These effects were counteracted by orchidectomy in male Sprague Dawley rats.

  19. Effect of interleukin-6 (IL-6) on the vascular smooth muscle contraction in abdominal aorta of rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Tang, Wen-Bo; Zhou, Yu-Qin; Zhao, Ting; Shan, Jing-Li; Sun, Peng; Yang, Ting-Ting; Chang, Xin-Wen; Li, Sen; Wang, Paulus S; Xie, Dong-Ping

    2011-10-31

    Patients with type 1 diabetes are at a risk of hypertension. However, the mechanisms behind the findings are not completely known. The aim of the present study was to investigate involvement of interleukin-6 (IL-6) on the contraction of abdominal aorta in rats with type 1 diabetes. IL-6 levels in the plasma of rats with streptozotocin (STZ)-induced diabetes were determined by ELISA. The abdominal aorta was dissected free of fat and connective tissues and then cut into spiral rings. The endothelium-denuded strip was vertically suspended in tissue chambers containing 5 ml Krebs solution at 37 degrees C and bubbled continuously with 95% O2-5% CO2. The effects of phenylephrine (Phe) on the contractile responses of abdominal aorta were recorded. The effects of IL-6 and anti-rat IL-6 antibody on the Phe-induced response were also examined. Plasma levels of IL-6 increased time-dependently in rats with STZ-induced diabetes. Phe caused concentration-dependent contraction in aortic rings. Phe-induced contractions were higher in vascular strips of STZ-induced diabetic rats than that of control rats. Pretreatment of vascular strips with IL-6 for 1 h did not cause contraction but enhanced the contraction in response to Phe. Treatment of the vascular strips with an anti-IL-6 antibody for 1 h decreased the Phe-induced contractions. These results suggest that IL-6 causes vascular smooth muscle contraction in abdominal aorta of rats with type 1 diabetes.

  20. Anti-platelet therapy with clopidogrel prevents endothelial dysfunction and vascular remodeling in aortas from hypertensive rats.

    Science.gov (United States)

    Giachini, Fernanda R; Leite, Romulo; Osmond, David A; Lima, Victor V; Inscho, Edward W; Webb, R Clinton; Tostes, Rita C

    2014-01-01

    The aim was to investigate the beneficial effects of clopidogrel in thoracic aorta function and structure and to characterize if P2Y12 receptors contribute to these effects. Male Sprague Dawley rats were infused with angiotensin II [(Ang II) 60 ng x min(-1), 14 days] or saline (control rats) and were simultaneously treated with clopidogrel (10 mg x kg(-1) x day(-1)) or vehicle. After 14 days, systolic blood pressure (mmHg) was similar in Ang II-hypertensive rats treated with clopidogrel or vehicle (199±9 vs. 190±11, respectively). Systolic blood pressure in control rats was not altered by clopidogrel treatment (128±1 vs. vehicle, 134±2). Endothelium-dependent relaxation induced by 2-MeS-ADP was decreased in aortas from vehicle-treated Ang II-hypertensive rats, compared to vehicle-treated control rats. This response was elicited via activation of P2Y1 and P2Y12 receptors. In the presence of L-NAME and indomethacin, 2-MeS-ADP induced contraction and this response was augmented in vehicle-treated Ang II-hypertensive rats, compared to vehicle-treated control rats. The contraction to 2-MeS-ADP was evoked by P2Y13 and P2Y12 receptor activation. Clopidogrel-treatment did not normalize relaxation or contractile responses induced by 2-MeS-ADP in aortas from Ang II-hypertensive rats. P2Y1 and P2Y12 protein expression was increased, whereas P2Y13 receptor expression was reduced in aorta from vehicle-treated Ang II-hypertensive rats. Endothelium-dependent relaxation upon acetylcholine-stimulation was reduced in vehicle-treated Ang II-hypertensive rats, and clopidogrel treatment was effective in improving endothelial function. Clopidogrel also prevented vascular remodeling, evidenced by augmented media thickness in aortas from Ang II-hypertensive rats. Clopidogrel has beneficial effects on the aortic endothelium of Ang II-hypertensive rats, but its effects do not seem to be directly related to the presence of P2Y12 receptors in this vessel.

  1. Anti-Platelet Therapy with Clopidogrel Prevents Endothelial Dysfunction and Vascular Remodeling in Aortas from Hypertensive Rats

    Science.gov (United States)

    Giachini, Fernanda R.; Leite, Romulo; Osmond, David A.; Lima, Victor V.; Inscho, Edward W.; Webb, R. Clinton; Tostes, Rita C.

    2014-01-01

    The aim was to investigate the beneficial effects of clopidogrel in thoracic aorta function and structure and to characterize if P2Y12 receptors contribute to these effects. Male Sprague Dawley rats were infused with angiotensin II [(Ang II) 60 ng.min−1, 14 days] or saline (control rats) and were simultaneously treated with clopidogrel (10 mg.kg−1.day−1) or vehicle. After 14 days, systolic blood pressure (mmHg) was similar in Ang II-hypertensive rats treated with clopidogrel or vehicle (199±9 vs. 190±11, respectively). Systolic blood pressure in control rats was not altered by clopidogrel treatment (128±1 vs. vehicle, 134±2). Endothelium-dependent relaxation induced by 2-MeS-ADP was decreased in aortas from vehicle-treated Ang II-hypertensive rats, compared to vehicle-treated control rats. This response was elicited via activation of P2Y1 and P2Y12 receptors. In the presence of L-NAME and indomethacin, 2-MeS-ADP induced contraction and this response was augmented in vehicle-treated Ang II-hypertensive rats, compared to vehicle-treated control rats. The contraction to 2-MeS-ADP was evoked by P2Y13 and P2Y12 receptor activation. Clopidogrel-treatment did not normalize relaxation or contractile responses induced by 2-MeS-ADP in aortas from Ang II-hypertensive rats. P2Y1 and P2Y12 protein expression was increased, whereas P2Y13 receptor expression was reduced in aorta from vehicle-treated Ang II-hypertensive rats. Endothelium-dependent relaxation upon acetylcholine-stimulation was reduced in vehicle-treated Ang II-hypertensive rats, and clopidogrel treatment was effective in improving endothelial function. Clopidogrel also prevented vascular remodeling, evidenced by augmented media thickness in aortas from Ang II-hypertensive rats. Clopidogrel has beneficial effects on the aortic endothelium of Ang II-hypertensive rats, but its effects do not seem to be directly related to the presence of P2Y12 receptors in this vessel. PMID:24638017

  2. Multi-detector row computed tomographic evaluation of a rare type of complete vascular ring: Double aortic arch with atretic left arch distal to the origin of left subclavian artery

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Ying Ying; Fu, Ching Yun; Wei, Hao Ji; Tsai, I Chen; Chen, Clayton Chi Chang [Taichung Veterans General Hospital, Taichung (China)

    2013-10-15

    Double aortic arch with an atretic left arch distal to the origin of left subclavian artery was diagnosed with multi-detector row computed tomography (MDCT) in two children with dysphagia. This rare type of complete vascular ring is clinically important because it may be confused with right aortic arch in mirror imaging. Anatomic details of this rare type of complete vascular ring demonstrated on MDCT facilitated appropriate surgical treatment.

  3. Valsartan attenuates intimal hyperplasia in balloon-injured rat aortic arteries through modulating the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis.

    Science.gov (United States)

    Li, Yonghong; Cai, Shanglang; Wang, Qixin; Zhou, Jingwei; Hou, Bo; Yu, Haichu; Ge, Zhiming; Guan, Renyan; Liu, Xu

    2016-05-15

    The role of the Mas receptor in the activity of valsartan against intimal hyperplasia is unclear. Herein, we investigated the role of the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis on the activity of valsartan against intimal hyperplasiain balloon-injured rat aortic arteries. Wistar rats were randomized equally into the sham control group, injured group, and injured plus valsartan (20 mg/kg/d)-treated group. Valsartan significantly attenuated the vascular smooth muscle cell proliferation and intimal and medial thickening on days 14 and 28 after injury. The angiotensin-(1-7) levels as well as ACE2 and Mas receptor mRNA/protein expression were significantly decreased in the injured rats, compared to the uninjured rats; meanwhile, the angiotensin II level as well as the ACE and AT1 receptor mRNA/protein expression were increased (all P Mas receptor mRNA/protein expression but decreased the angiotensin II level, ACE and AT1 receptor mRNA/protein expression, as well as the p-ERK protein expression, compared to the injured group (all P Mas axis as well as inhibition of the ACE-angiotensin II-AT1 and p-ERK pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Uraemic hyperparathyroidism causes a reversible inflammatory process of aortic valve calcification in rats.

    Science.gov (United States)

    Shuvy, Mony; Abedat, Suzan; Beeri, Ronen; Danenberg, Haim D; Planer, David; Ben-Dov, Iddo Z; Meir, Karen; Sosna, Jacob; Lotan, Chaim

    2008-08-01

    Renal failure is associated with aortic valve calcification (AVC). Our aim was to develop an animal model for exploring the pathophysiology and reversibility of AVC, utilizing rats with diet-induced kidney disease. Sprague-Dawley rats (n = 23) were fed a phosphate-enriched, uraemia-inducing diet for 7 weeks followed by a normal diet for 2 weeks ('diet group'). These rats were compared with normal controls (n = 10) and with uraemic controls fed with phosphate-depleted diet ('low-phosphate group', n = 10). Clinical investigations included serum creatinine, phosphate and parathyroid hormone (PTH) levels, echocardiography, and multislice computed tomography. Pathological examinations of the valves included histological characterization, Von Kossa staining, and antigen and gene expression analyses. Eight diet group rats were further assessed for reversibility of valve calcification following normalization of their kidney function. At 4 weeks, all diet group rats developed renal failure and hyperparathyroidism. At week 9, renal failure resolved with improvement in the hyperparathyroid state. Echocardiography demonstrated valve calcifications only in diet group rats. Tomographic calcium scores were significantly higher in the diet group compared with controls. Von Kossa stain in diet group valves revealed calcium deposits, positive staining for osteopontin, and CD68. Gene expression analyses revealed overexpression of osteoblast genes and nuclear factor kappaB activation. Valve calcification resolved after diet cessation in parallel with normalization of PTH levels. Resolution was associated with down-regulation of inflammation and osteoblastic features. Low-phosphate group rats developed kidney dysfunction similar to that of the diet group but with normal levels of PTH. Calcium scores and histology showed only minimal valve calcification. We developed an animal model for AVC. The process is related to disturbed mineral metabolism. It is associated with inflammation and

  5. Aortic stiffness is associated with the central retinal arteriolar equivalent and retinal vascular fractal dimension in a population along the southeastern coast of China.

    Science.gov (United States)

    Lin, Fan; Zhu, Pengli; Huang, Feng; Li, Qiaowei; Yuan, Yin; Gao, Zhonghai; Yu, Peng; Lin, Jing; Chen, Falin

    2015-05-01

    The objective of this study was to evaluate the association of the central retinal arteriolar equivalent (CRAE) and the retinal vascular fractal dimension, two quantitative parameters that reflect microcirculation, with aortic stiffness. In this cross-sectional study, we identified the cardiovascular risk factors in 2169 subjects using a health questionnaire, physical examinations and laboratory examinations. We evaluated the aortic stiffness using noninvasive brachial-ankle pulse wave velocity (baPWV) and assessed the microcirculatory alterations with CRAE and retinal vascular fractal dimension, which were measured using fundus photography and semiautomatic quantitative software, respectively. The increase in baPWV (Q1-Q4) correlated with an increased likelihood of the central retinal artery narrowing and a reduction in the retinal vascular fractal dimension. Further adjustment of the cardiovascular risk factors diminished the association between baPWV and CRAE, but increased the association between baPWV and retinal vascular fractal dimension. Elevated baPWV correlates with reduced CRAE and retinal vascular fractal dimension. Such a finding supports macrocirculation- and microcirculation-associated hypotheses.

  6. Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats

    Directory of Open Access Journals (Sweden)

    Antunes Edson

    2008-05-01

    Full Text Available Abstract Background Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings. Methods Male Wistar rats were divided into sedentary (SD; trained (TR; sedentary diet (SDD and trained diet (TRD groups. Run training (RT was performed in sessions of 60 min, 5 days/week for 12 weeks (70–80% VO2max. Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx- were measured. Concentration-response curves to acetylcholine (ACh and sodium nitroprusside (SNP were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1 was assessed by Western blotting. Results High caloric diet increased triglycerides concentration (SDD: 216 ± 25 mg/dl and exercise training restored to the baseline value (TRD: 89 ± 9 mg/dl. Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 ± 0.1 and TRD: 1.24 ± 0.3 ng/ml as compared to sedentary animals (SD: 0.87 ± 0.1 and SDD: 2.57 ± 0.3 ng/ml. On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 ± 6; TR: 140 ± 8; SDD: 156 ± 8 and TRD 153 ± 9 mg/dl. Neither high caloric diet nor RT modified NOx- levels (SD: 27 ± 4; TR: 28 ± 6; SDD: 27 ± 3 and TRD: 30 ± 2 μM. Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%, but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups or mesenteric rings (10%, for TR and 17%, to TRD groups that was accompanied by up-regulation of SOD-1

  7. (Tissue PET) Vascular metabolic imaging and peripheral plasma biomarkers in the evolution of chronic aortic dissections.

    Science.gov (United States)

    Sakalihasan, Natzi; Nienaber, Christoph A; Hustinx, Roland; Lovinfosse, Pierre; El Hachemi, Mounia; Cheramy-Bien, Jean-Paul; Seidel, Laurence; Lavigne, Jean-Paul; Quaniers, Janine; Kerstenne, Marie-Ange; Courtois, Audrey; Ooms, Annie; Albert, Adelin; Defraigne, Jean-Olivier; Michel, Jean-Baptiste

    2015-06-01

    Despite adequate medical management, dissection of the descending aorta (type B) may develop complications, including aneurysmal progression and eventually rupture. Partial false lumen thrombosis has been identified as a marker of adverse evolution in chronic dissection. The aim of this study was to test the ability of complementary information, provided by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) and peripheral biomarkers, to add pathophysiological significance and a prognostic value to morphological data. We explored serial aortic (18)F-FDG uptake by PET/CT imaging and plasma biomarkers in a series of 23 patients with type B dissection to predict complications from initial data and to investigate potential associations with aneurysmal expansion during follow-up. Complications occurred in 17 patients. Acute initial characteristics associated with complications were male gender (P = 0.021), arterial hypertension (P = 0.040), aortic dissection diameter (P = 0.0086), partial thrombosis of the false channel (P = 0.0046), and enhanced focal (18)F-FDG uptake (P = 0.045). During follow-up (mean 16.7 ± 8.0 months), aneurysmal expansion was associated with false lumen morphology (P< 0.0001), quantitative (18)F-FDG uptake, (P = 0.0029), elevated plasma concentrations of biomarkers of platelets (P-selectin, P = 0.0009) and thrombin activation (TAT complexes, P = 0.0075), and fibrinolysis (PAP complexes, P < 0.0001; D-dimers, P = 0.0006). Plasma markers of coagulation and fibrinolysis were related to false channel morphology, suggesting that thrombus biological dynamics may drive progressive expansion of type B dissections. Enhanced FDG uptake may be considered as a complementary imaging marker associated with secondary complications in type B dissections. During follow-up, aneurysmal progression is related to PET/CT and biomarkers of thrombus renewal and lysis. Published on behalf of the European Society of Cardiology

  8. Vascular Aldosterone Production at the Pre-Diabetic Stage of Young Otsuka Long-Evans Tokushima Fatty (OLETF Rats, Compared with Long-Evans Tokushima Otsuka (LETO Rats

    Directory of Open Access Journals (Sweden)

    Yoko Matsuzawa

    2013-12-01

    Full Text Available We examined the ability of aortic smooth muscle cells (AoSMC prepared from spontaneously diabetic rats to produce aldosterone (Aldo and the regulatory mechanism that controls their Aldo production. AoSMC of 6 week-old Long-Evans Tokushima Otsuka (LETO: the control group and 6 week-old Otsuka Long-Evans Tokushima Fatty (OLETF: the type 2 diabetes group rats were used in the present experiments. CYP11B2 (Aldo synthetase mRNA expression was detected in both the LETO and OLETF AoSMC. Basal Aldo production was significantly greater (4–5 fold higher in the OLETF AoSMC culture medium than in the LETO AoSMC culture medium. When AoSMC were co-incubated with high-density lipoproteins (HDL, supplying cholesterol as a substrate for steroidogenesis in rats, angiotensin II (AII significantly increased greater Aldo production in the OLETF AoSMC than in the LETO AoSMC. The present data suggested that future onset of diabetic vascular dysfunction is partly caused by excess Aldo production by AoSMC in young OLETF rats. Concomitant stimulation by HDL and AII resulted in elevated Aldo production in the OLETF and the LETO AoSMC, and also demonstrated that AII-induced Aldo production is greatly enhanced by HDL in OLETF, rather than in LETO. In conclusion, our data clearly demonstrated that Aldo production in the OLETF AoSMC was significantly higher than in the LETO AoSMC, suggesting possible future onset of vascular dysfunction in diabetes, induced by local Aldo production in the AoSMC.

  9. A Single Resistance Exercise Session Improves Aortic Endothelial Function in Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Thaís de Oliveira Faria

    Full Text Available Abstract Background: Physical exercise is an important tool for the improvement of endothelial function. Objective: To assess the effects of acute dynamic resistance exercise on the endothelial function of spontaneously hypertensive rats (SHR. Methods: Ten minutes after exercise, the aorta was removed to evaluate the expression of endothelial nitric oxide synthase (eNOS, phosphorylated endothelial nitric oxide synthase (p-eNOS1177 and inducible nitric oxide synthase (iNOS and to generate concentration-response curves to acetylcholine (ACh and to phenylephrine (PHE. The PHE protocol was also performed with damaged endothelium and before and after NG-nitro-L-arginine methyl ester (L-NAME and indomethacin administration. The maximal response (Emax and the sensitivity (EC50 to these drugs were evaluated. Results: ACh-induced relaxation increased in the aortic rings of exercised (Ex rats (Emax= -80 ± 4.6%, p < 0.05 when compared to those of controls (Ct (Emax = -50 ± 6.8%. The Emax to PHE was decreased following exercise conditions (95 ± 7.9%, p < 0.05 when compared to control conditions (120 ± 4.2%. This response was abolished after L-NAME administration or endothelial damage. In the presence of indomethacin, the aortic rings' reactivity to PHE was decreased in both groups (EC50= Ex -5.9 ± 0.14 vs. Ct -6.6 ± 0.33 log µM, p < 0.05 / Emax = Ex 9.5 ± 2.9 vs. Ct 17 ± 6.2%, p < 0.05. Exercise did not alter the expression of eNOS and iNOS, but increased the level of p-eNOS. Conclusion: A single resistance exercise session improves endothelial function in hypertensive rats. This response seems to be mediated by increased NO production through eNOS activation.

  10. Alpha-tocopherol and BAY 11-7082 reduce vascular cell adhesion molecule in human aortic endothelial cells.

    Science.gov (United States)

    Catalán, Ursula; Fernández-Castillejo, Sara; Pons, Laia; Heras, Mercedes; Aragonés, Gemma; Anglès, Neus; Morelló, Jose-Ramon; Solà, Rosa

    2012-01-01

    In endothelial dysfunction, vascular cell adhesion molecule-1 (VCAM-1), E-selectin and intercellular adhesion molecule-1 (ICAM-1) expression (collectively termed cell adhesion molecules; CAMs) increase at sites of atherosclerosis and are stimulated by proinflammatory cytokines such as tumor necrosis factor-α (TNF-α). We evaluated the effect of alpha-tocopherol (AT; 10-150 µM) and BAY 11-7082 (BAY; 0.1 or 1 µM) on CAMs mRNA expression as well as their protein in soluble release form (sCAMs) in human aortic endothelial cells (HAECs) activated by TNF-α (1 or 10 ng/ml). Also, we determined the extent of lymphocyte adhesion to activated HAECs. BAY reduced VCAM-1, E-selectin and ICAM-1 mRNA expression by 30, 30 and 10%, respectively. Furthermore, protein reduction of sVCAM-1 by 70%, sE-selectin by 51% and sICAM-1 by 25% compared to HAECs stimulated by TNF-α was observed (p adhesion to human Jurkat T lymphocytes was higher compared to nonactivated HAECs (p adhesion (p cell adhesion, while AT selectively inhibits VCAM-1; both induce endothelial dysfunction improvement. Copyright © 2012 S. Karger AG, Basel.

  11. Data on the effects of losartan on protein expression, vascular reactivity and antioxidant capacity in the aorta of ethanol-treated rats

    Directory of Open Access Journals (Sweden)

    Carla S. Ceron

    2017-04-01

    Full Text Available We describe the effects of losartan, a selective AT1 receptor antagonist on the alterations induced by treatment with ethanol in the rat aorta. The data shown here are related to the article entitled “Angiotensin type 1 receptor mediates chronic ethanol consumption-induced hypertension and vascular oxidative stress” (P. Passaglia, C.S. Ceron, A.S. Mecawi, J. Antunes-Rodrigues, E.B. Coelho, C.R. Tirapelli, 2015 [1]. Here we include new data on the protective effect of losartan against ethanol-induced oxidative stress. Male Wistar rats treated for 2 weeks with ethanol (20%, vol./vol. exhibited increased aortic production of reactive oxygen species (ROS and losartan (10 mg/kg/day; p.o. gavage prevented this response. Ethanol did not alter the expression of eNOS in the rat aorta. Losartan prevented ethanol-induced increase in the aortic expression of nNOS. Neither ethanol nor losartan affected superoxide dismutase (SOD or catalase (CAT activities in the rat aorta. Treatment with ethanol increased the contraction induced by phenylephrine in both endothelium-intact and endothelium-denuded aortas and these responses were prevented by losartan. Conversely, neither ethanol nor losartan affected the endothelium-dependent relaxation induced by acetylcholine.

  12. Selective cyclooxygenase-1 inhibition improves collateral vascular reactivity in biliary cirrhotic rats

    Directory of Open Access Journals (Sweden)

    Ching-Chih Chang

    2013-10-01

    Conclusion: There was no significant hemodynamic change and renal toxicity after acute administration of COX inhibitor in the FBDL-induced cirrhotic rats. Preincubation of selective COX-1, but not COX-2, inhibitor could enhance collateral vascular response to AVP, indicating that COX-1 plays a major role in the collateral vascular reactivity.

  13. Acupuncture reversed hippocampal mitochondrial dysfunction in vascular dementia rats.

    Science.gov (United States)

    Li, Hui; Liu, Yi; Lin, Li-Ting; Wang, Xue-Rui; Du, Si-Qi; Yan, Chao-Qun; He, Tian; Yang, Jing-Wen; Liu, Cun-Zhi

    2016-01-01

    Hippocampal mitochondrial dysfunction due to oxidative stress has been considered to play a major role in the pathogenesis of vascular dementia (VD). Previous studies suggested that acupuncture could improve cerebral hypoperfusion-induced cognitive impairments. However, whether hippocampal mitochondria are associated with this cognitive improvement remains unclear. In this study, an animal model of VD was established via bilateral common carotid arteries occlusion (BCCAO) to investigate the alterations of cognitive ability and hippocampal mitochondrial function. BCCAO rats showed impairments in hippocampal mitochondrial function, overproduction of reactive oxygen species (ROS) and learning and memory deficits. After two-week acupuncture treatment, BCCAO-induced spatial learning and memory impairments as shown in Morris water maze were ameliorated. Hippocampal mitochondrial respiratory complex enzymes (complex I, II, IV) activities and cytochrome c oxidase IV expression significantly increased, which might contribute to the reduction of hippocampal ROS generation. In addition, acupuncture significantly improve mitochondrial bioenergy parameters such as mitochondrial respiratory control rate and membrane potential not PDH A1 expression. Placebo-acupuncture did not produce similar therapeutic effects. These findings suggested that acupuncture reversed BCCAO-induced hippocampal mitochondrial dysfunction, which might contribute to its prevention on cognitive deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Hepatic oxidative stress, genotoxicity and vascular dysfunction in lean or obese zucker rats

    DEFF Research Database (Denmark)

    Løhr, Mille; Folkmann, Janne Kjærsgaard; Sheykhzade, Majid

    2015-01-01

    Metabolic syndrome is associated with increased risk of cardiovascular disease, which could be related to oxidative stress. Here, we investigated the associations between hepatic oxidative stress and vascular function in pressurized mesenteric arteries from lean and obese Zucker rats at 14, 24...... of the vascular wall. There was increased maximal response to acetylcholine-mediated endothelium-dependent vasodilatation in both strains of rats. Collectively, the results indicate that obese Zucker rats only displayed a modest mesenteric vascular dysfunction, with no increase in hepatic oxidative stress...... and 37 weeks of age. Obese Zucker rats had more hepatic fat accumulation than their lean counterparts. Nevertheless, the obese rats had unaltered age-related level of hepatic oxidatively damaged DNA in terms of formamidopyrimidine DNA glycosylase (FPG) or human oxoguanine DNA glycosylase (hOGG1...

  15. 2′,3′-cAMP, 3′-AMP, and 2′-AMP inhibit human aortic and coronary vascular smooth muscle cell proliferation via A2B receptors

    Science.gov (United States)

    Ren, Jin; Gillespie, Delbert G.

    2011-01-01

    Rat vascular smooth muscle cells (VSMCs) from renal microvessels metabolize 2′,3′-cAMP to 2′-AMP and 3′-AMP, and these AMPs are converted to adenosine that inhibits microvascular VSMC proliferation via A2B receptors. The goal of this study was to test whether this mechanism also exists in VSMCs from conduit arteries and whether it is similarly expressed in human vs. rat VSMCs. Incubation of rat and human aortic VSMCs with 2′,3′-cAMP concentration-dependently increased levels of 2′-AMP and 3′-AMP in the medium, with a similar absolute increase in 2′-AMP vs. 3′-AMP. In contrast, in human coronary VSMCs, 2′,3′-cAMP increased 2′-AMP levels yet had little effect on 3′-AMP levels. In all cell types, 2′,3′-cAMP increased levels of adenosine, but not 5′-AMP, and 2′,3′-AMP inhibited cell proliferation. Antagonism of A2B receptors (MRS-1754), but not A1 (1,3-dipropyl-8-cyclopentylxanthine), A2A (SCH-58261), or A3 (VUF-5574) receptors, attenuated the antiproliferative effects of 2′,3′-cAMP. In all cell types, 2′-AMP, 3′-AMP, and 5′-AMP increased adenosine levels, and inhibition of ecto-5′-nucleotidase blocked this effect of 5′-AMP but not that of 2′-AMP nor 3′-AMP. Also, 2′-AMP, 3′-AMP, and 5′-AMP, like 2′,3′-cAMP, exerted antiproliferative effects that were abolished by antagonism of A2B receptors with MRS-1754. In conclusion, VSMCs from conduit arteries metabolize 2′,3′-cAMP to AMPs, which are metabolized to adenosine. In rat and human aortic VSMCs, both 2′-AMP and 3′-AMP are involved in this process, whereas, in human coronary VSMCs, 2′,3′-cAMP is mainly converted to 2′-AMP. Because adenosine inhibits VSMC proliferation via A2B receptors, local vascular production of 2′,3′-cAMP may protect conduit arteries from atherosclerosis. PMID:21622827

  16. Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat.

    Science.gov (United States)

    Szabo, S; Trier, J S; Brown, A; Schnoor, J

    1985-01-01

    The hypothesis that vascular injury contributes to the development of hemorrhagic erosions after intragastric administration of ethanol has been examined in the rat using vascular tracers. Extravasation of intravenously injected Evans blue into the gastric wall and into gastric contents was used as an indicator of vascular permeability. India ink and monastral blue, which label damaged blood vessels, were used to demonstrate vascular injury morphologically. Intragastric instillation of 75% and 100% ethanol induced increased vascular permeability within 1-3 min and resulted in monastral blue labeling of vessels in 13% and 17%, respectively, of the glandular mucosa within 1 min. After 1 h of 100% ethanol exposure, the areal density of monastral blue-stained blood vessels did not increase compared with that seen at 1 min, but the areal density of grossly visible hemorrhagic lesions increased strikingly and approximated that of vessel staining. The hemorrhagic erosions consistently occurred in regions of glandular mucosa where vessels were stained with monastral blue. Pretreatment with prostaglandin F2 beta or cysteamine reduced ethanol-induced Evans blue extravasation and monastral blue staining of mucosal blood vessels but did not reduce histologic evidence of gastric surface cell damage in the glandular mucosa. As increased vascular permeability and morphologically detectable vascular lesions consistently preceded the development of grossly visible hemorrhagic erosions in the glandular mucosa, we suggest that vascular injury is an early pathogenetic factor in the development of ethanol-induced gastric hemorrhagic erosions. The data also indicate that the degree of vascular damage, unlike the injury to surface epithelial cells, is reduced by pretreatment with prostaglandin F2 beta or the sulfhydryl cysteamine.

  17. Effect of sarpogrelate hydrochloride, a 5-hydroxytryptamine2 receptor antagonist, on allograft arteriosclerosis after aortic transplantation in rats.

    Science.gov (United States)

    Watada, Susumu; Harada, Hirohisa; Matsubara, Kentaro; Obara, Hideaki; Matsumoto, Kenji; Ando, Nobutoshi; Kitagawa, Yuko

    2013-12-01

    Sarpogrelate hydrochloride, a 5-hydroxytryptamine2 receptor antagonist, is known to prevent serotonin-induced neointimal hyperplasia. We examined the effect of this agent on allograft arteriosclerosis in a rat model of aortic transplantation. Rats were given an aortic isograft or allograft and oral administration of either saline vehicle alone or 20mg/kg daily of sarpogrelate for 8 weeks. The grafts were then harvested, and the lumen diameter and the thickness of the intima and media were measured. Comparisons were made between measurement results in isografts and allografts from rats treated and not treated with sarpogrelate. Immunohistochemistry assessments were used to detect expression of serotonin in graft specimens. For both allografts and isografts, significantly less intimal thickening was observed in specimens from rats given sarpogrelate compared with rats given saline. Sarpogrelate had no effect on medial thickening in either graft type. Serotonin was detected in allografts from rats given saline alone but not in allografts from rats given sarpogrelate or in isografts. Sarpogrelate hydrochloride may mitigate arteriosclerosis in allografts. Platelet aggregation and serotonin may be correlated with intimal thickening associated with chronic rejection. © 2013. Published by Elsevier B.V. All rights reserved.

  18. The Diterpene Sclareol Vascular Effect in Normotensive and Hypertensive Rats.

    Science.gov (United States)

    Campos, Debora Ribeiro; Celotto, Andrea Carla; Albuquerque, Agnes Afrodite S; Ferreira, Luciana Garros; Monteiro, Ariadne Santana E Neves; Coelho, Eduardo Barbosa; Evora, Paulo Roberto Barbosa

    2017-06-29

    The diterpene Sclareol has antimicrobial action, cytotoxic and cytostatic effects and anti-tumor activities. However, researches on the cardiovascular system are scarce. This study was designed to investigate the mechanisms involved in the Sclareol cardiovascular effect in normotensive and hypertensive rats. The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The effect of sclareol on blood pressure was performed by using three dose (10, 20 and 40 mg/kg). Cumulative dose-response curves for Sclareol were determined for endothelium-intact and endothelium-denuded aortic rings in presence or absence of L-NAME and ODQ. The NOx levels were measure in the plasma sample. The Sclareol administration in vivo caused a significant reduction in blood pressure in both groups. In vitro the sclareol promoted relaxation in aorta, with endothelium, pre-contracted to Phe. The inhibitors of the nitric oxide synthase and soluble guanylate cyclase were as efficient as the removal of endothelium, in inhibiting the Sclareol-induced relaxation. Otherwise, it was no change of NOx. Also, for unknown reasons, the Sclareol is not selective for hypertensive animals. The diterpene Sclareol showed in vivo hypotensive and in-vitro vasodilator effects; The chemiluminescence plasmatic NO analysis showed no significant difference between groups and The Sclareol exhibit better effect on normotensive than hypertensive animals to reduce blood pressure. It is concluded that the diterpenes metabolites would be a promising source prototype for the development of new agents in the cardiovascular therapy. O diterpeno Esclareol tem ação antimicrobiana, efeitos citotóxicos e citostáticos e atividades antitumorais. No entanto, pesquisas sobre o sistema cardiovascular são escassas. Este estudo foi desenvolvido para investigar os mecanismos envolvidos no efeito cardiovascular de Esclareol em ratos normotensos e hipertensos. A hipertensão arterial foi promovida utilizando modelo de

  19. Impact of Mean Platelet Volume on Combined Safety Endpoint and Vascular and Bleeding Complications following Percutaneous Transfemoral Transcatheter Aortic Valve Implantation

    Directory of Open Access Journals (Sweden)

    Caroline J. Magri

    2013-01-01

    Full Text Available Background. Vascular and bleeding complications remain important complications in patients undergoing percutaneous transfemoral transcatheter aortic valve implantation (TF-TAVI. Platelets play an important role in bleeding events. Mean platelet volume (MPV is an indicator of platelet activation. The objective of this study was to assess whether low MPV is an indicator of major vascular and bleeding complications following TF-TAVI. Methods. A retrospective cohort study of 330 subjects undergoing TF-TAVI implantation was performed. The primary study endpoint was the occurrence of combined safety endpoint (CSEP; secondary endpoints included major vascular complications and life-threatening bleeding. Endpoints were defined according to Valve Academic Research Consortium 2. Results. The CSEP at 30 days was reached in 30.9%; major vascular complications were observed in 14.9% while life-threatening bleeding occurred in 20.6%. Logistic Euroscore and MPV were independent predictors of CSEP. Predictors of vascular complications were female sex, previous myocardial infarction, red blood cell distribution width (RDW, and MPV while predictors of life-threatening bleeding were peripheral arterial disease, RDW, and MPV. Conclusion. A low baseline MPV was shown for the first time to be a significant predictor of CSEP, major vascular complications, and life-threatening bleeding following TF-TAVI.

  20. MiR-21 inhibits c-Ski signaling to promote the proliferation of rat vascular smooth muscle cells.

    Science.gov (United States)

    Li, Jun; Zhao, Li; He, Xie; Yang, Ting; Yang, Kang

    2014-04-01

    Previously, we reported that the decrease of endogenous c-Ski expression is implicated in the progression of vascular smooth muscle cell (VSMC) proliferation after arterial injury. However, the molecular mechanism of the down-regulation of c-Ski is not clear. In this study, a potential miR-21 recognition element was identified in the 3'-untranslated region (UTR) of rat c-Ski mRNA. A reporter assay revealed that miR-21 could recognize the miR-21 recognition element of c-Ski mRNA. In A10 rat aortic smooth muscle cells, overexpression of miR-21 significantly inhibited the expression of c-Ski protein and promoted cell proliferation, which could be blocked by inhibition of miR-21 or overexpression of c-Ski. Further investigation demonstrated that the effect of miR-21 on VSMC proliferation resulted from negative regulation of c-Ski to suppress p38-p21/p27 signaling, the downstream pathway of c-Ski in VSMCs. These results indicate that c-Ski is a target gene of miR-21. miR-21 specifically binds to the 3'-untranslated region of c-Ski and negatively regulates c-Ski expression to diminish the protective effects of c-Ski and stimulate VSMC proliferation in the progression of arterial injury. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. [Effects of ANP upon ion pump activity and gene expression in aortic smooth muscle cells from spontaneously hypertensive rats].

    Science.gov (United States)

    Zhang, Gui-hai; Shang, Qian-hui; Jiang, Qian-feng; Wu, Ze-bing; Liu, Zu-lin; Wan, Wei-hong

    2009-11-03

    To explore the effects of atrial natriuretic peptide (ANP) upon the activities of Na(+), K(+)-ATPase, Ca(2+)-ATPase and mRNA expression levels of Na(+), K(+)-ATPase alpha(1)-subunit and plasma membrane Ca(2+)-ATPase isoform 1 (PMCA1) in cultured thoracic aortic vascular smooth muscle cells (ASMCs) isolated from spontaneously hypertensive rats (SHR). ASMCs isolated from 14-week-old male SHR and Wistar-Kyoto (WKY) rats were interference-cultured in different doses of ANP and Angiotensin II (AngII). The contents of ANP and AngII in supernatant from ASMCs were measured by radioimmunoassay. The activities of the above two ATPases were measured by biochemistry and enzymology. RT-PCR assay was employed to determine the relative levels of Na(+), K(+)-ATPase alpha(1)-subunit and PMCA1 mRNA in ASMCs. The ANP level of supernatant in SHR ASMCs was significantly lower than those from WKY control [(7.3 +/- 2.4) pg x 10(-6) cells vs (19.3 +/- 3.3) pg x 10(-6) cells, P ANP improved obviously the activities of Na(+), K(+)-ATPase, Ca(2+)-ATPase and expression of alpha(1)-subunit, PMCA1 mRNA in a does-dependent manner (P ANP antagonized the effects of AngII (1 x 10(-7) mol/L) upon the activities of two ATPases and the expression of Na(+), K(+)-ATPase alpha(1)-subunit PMCA1 mRNA (P ANP antagonized the effects of AngII (1 x 10(-7) mol/L) upon the activity of Ca(2+)-ATPase and the expression of PMCA1 mRNA (P 0.05). The decreased activities of Na(+), K(+)-ATPase and Ca(2+)-ATPase may be related to the abnormal autocrine of ANP and AngII in ASMC of SHR. ANP can antagonize the effects of AngII upon the activities of two ATPases and the expression of Na(+), K(+)-ATPase alpha(1)-subunit PMCA1 mRNA.

  2. Vascular endothelial function is improved by oral glycine treatment in aged rats.

    Science.gov (United States)

    Gómez-Zamudio, Jaime H; García-Macedo, Rebeca; Lázaro-Suárez, Martha; Ibarra-Barajas, Maximiliano; Kumate, Jesús; Cruz, Miguel

    2015-06-01

    Glycine has been used to reduce oxidative stress and proinflammatory mediators in some metabolic disorders; however, its effect on the vasculature has been poorly studied. The aim of this work was to explore the effect of glycine on endothelial dysfunction in aged rats. Aortic rings with intact or denuded endothelium were obtained from untreated or glycine-treated male Sprague-Dawley rats at 5 and 15 months of age. Concentration-response curves to phenylephrine (PHE) were obtained from aortic rings incubated with N(G)-nitro-l-arginine methyl ester (l-NAME), superoxide dismutase (SOD), indomethacin, SC-560, and NS-398. Aortic mRNA expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase 4 (NOX-4), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), tumour necrosis factor (TNF)-α, and interleukin-1 β was measured by real time RT-PCR. The endothelial modulation of the contraction by PHE was decreased in aortic rings from aged rats. Glycine treatment improved this modulator effect and increased relaxation to acetylcholine. Glycine augmented the sensitivity for PHE in the presence of l-NAME and SOD. It also reduced the contraction by incubation with indomethacin, SC-560, and NS-398. Glycine increased the mRNA expression of eNOS and decreased the expression of COX-2 and TNF-α. Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.

  3. Vasorelaxant effects of Angelica decursiva root on isolated rat aortic rings.

    Science.gov (United States)

    Kim, Bumjung; Kwon, Youngki; Lee, Somin; Lee, Kyungjin; Ham, Inhye; Choi, Ho-Young

    2017-10-02

    Hypertension is one of the most important risk factors for cardiovascular disease (CVD) and a worldwide problem. Despite increases in the development of synthetic drugs for hypertension treatment, the rate of untreated and uncontrolled hypertension remains high. These drugs are effective, but can also cause side effects. Approximately 80% of the world population uses herbal medicines because of their low toxicity and better acceptability by the human body. Therefore, we attempted to identify natural medications for treating hypertension. The 70% ethanol extract of Angelica decursiva root (ADE) shows strong vasorelaxant potential, but no studies have investigated the mechanisms underlying the vasorelaxation effect of A. decursiva. Dried root of A. decursiva was identified by DNA sequencing and was extracted once with 1 L 70% ethanol (EtOH) for 3 h in a reflux apparatus at 70 °C. ADE was evaluated for its vasorelaxant effects in rat thoracic aortas. Various inhibitors of ADE-induced vasorelaxation were used. ADE showed vasorelaxant effects on the intact and denuded endothelium of aortic rings pre-contracted with phenylephrine and KCl in Krebs-Henseleit solution. Tetraethylammonium and 4-aminopyridine did not alter ADE-induced vasorelaxation. However, the vasorelaxant effect of ADE was partially inhibited by pre-treatment with glibenclamide an ATP-sensitive K(+) channel blocker. Furthermore, ADE concentration-dependently inhibited Ca(2+) supplementation-induced vasoconstriction of aortic rings that had been pretreated with phenylephrine or KCl in Ca(2+)-free Krebs-Henseleit solution. These results suggest that ADE-induced vasorelaxation occurred in an endothelium-independent manner. The vasorelaxant effects of ADE were correlated with blockade of the KATP channel and inhibition of Ca(2+) influx via receptor-operative Ca(2+) channels or voltage-dependent Ca(2+) channels.

  4. Pulmonary vascular responsiveness in rats following neonatal exposure to high altitude or carbon monoxide

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, A.; Penney, D.G. (Colorado State Univ., Fort Collins, CO (United States) Wayne State Univ., Detroit, MI (United States))

    1993-01-01

    Exposure of adult and neonatal rats to high altitude increases pulmonary vascular responsiveness during the exposure. A study was undertaken to determine if a short exposure of neonatal rats to either high-altitude or carbon monoxide (CO) hypoxia would cause persistent alterations in pulmonary vascular responsiveness postexposure. One-day-old male Sprague-Dawley rats were obtained as 16 litters of 10-12 pups each. At 2 days of age, 4 litters were exposed to CO (500 ppm) for 32 days, and 4 litters were exposed to ambient air (AIR) in Detroit (200 m). Another 4 litters were exposed to 3500 m altitude (ALT) in a chamber for 32 days, and 3 litters were exposed to ambient conditions in Fort Collins (CON, 1524 m). After the exposures, all rats were maintained at 1524 m. At 2, 40, 76 and 112 days postexposure, lungs were isolated and perfused with Earle's salt solution (+Ficoll, 4 g%). Pulmonary vascular responsiveness was assessed by dose responses to angiotensin II (AII, 0.025-0.40 [mu]g) and acute hypoxia (3% O[sub 2] for 3 min). AII responses were higher in ALT vs CON rats at 2 and 40 days postexposure, but no differences were noted between CO and AIR rats. Baseline pulmonary vascular resistance and pulmonary arterial pressure (in isolated lungs) were higher in ALT rats at all four ages compared to the other three groups. Both the ALT and CO rats displayed hypertrophy of the right ventricle (RV) and the left ventricle (LV) at the termination of treatment and elevated hematocrit. LV hypertrophy and polycythemia regressed with time, but RV hypertrophy remained significant in the ALT rats through 112 days postexposure. The results indicate that neonatal exposure to ALT, but no CO, causes a persistent increase in pulmonary vascular responsiveness and RV hypertrophy for at least 112 days after termination of the exposure. 40 refs., 3 figs., 2 tabs.

  5. Intrahepatic Vascular Anatomy in Rats and Mice--Variations and Surgical Implications.

    Directory of Open Access Journals (Sweden)

    Constanze Sänger

    Full Text Available The intra-hepatic vascular anatomy in rodents, its variations and corresponding supplying and draining territories in respect to the lobar structure of the liver have not been described. We performed a detailed anatomical imaging study in rats and mice to allow for further refinement of experimental surgical approaches.LEWIS-Rats and C57Bl/6N-Mice were subjected to ex-vivo imaging using μCT. The image data were used for semi-automated segmentation to extract the hepatic vascular tree as prerequisite for 3D visualization. The underlying vascular anatomy was reconstructed, analysed and used for determining hepatic vascular territories.The four major liver lobes have their own lobar portal supply and hepatic drainage territories. In contrast, the paracaval liver is supplied by various small branches from right and caudate portal veins and drains directly into the vena cava. Variations in hepatic vascular anatomy were observed in terms of branching pattern and distance of branches to each other. The portal vein anatomy is more variable than the hepatic vein anatomy. Surgically relevant variations were primarily observed in portal venous supply.For the first time the key variations of intrahepatic vascular anatomy in mice and rats and their surgical implications were described. We showed that lobar borders of the liver do not always match vascular territorial borders. These findings are of importance for the design of new surgical procedures and for understanding eventual complications following hepatic surgery.

  6. Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Chu-Lin Chou

    Full Text Available Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group. Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L. These results suggest a protective role of calcitriol treatment on endothelial

  7. Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

    Science.gov (United States)

    Chou, Chu-Lin; Pang, Cheng-Yoong; Lee, Tony J F; Fang, Te-Chao

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose

  8. Vasopressor mechanisms in acute aortic coarctation hypertension

    Directory of Open Access Journals (Sweden)

    Salgado H.C.

    1997-01-01

    Full Text Available Angiotensin II (ANG II and vasopressin (AVP act together with the mechanical effect of aortic constriction in the onset of acute aortic coarctation hypertension. Blockade of ANG II and AVP V1 receptors demonstrated that ANG II acts on the prompt (5 min rise in pressure whereas AVP is responsible for the maintenance (30-45 min of the arterial pressure elevation during aortic coarctation. Hormone assays carried out on blood collected from conscious rats submitted to aortic constriction supported a role for ANG II in the early stage and a combined role for both ANG II and AVP in the maintenance of proximal hypertension. As expected, a role for catecholamines was ruled out in this model of hypertension, presumably due to the inhibitory effect of the sinoaortic baroreceptors. The lack of afferent feedback from the kidneys for AVP release from the central nervous system in rats with previous renal denervation allowed ANG II to play the major role in the onset of the hypertensive response. Median eminence-lesioned rats exhibited a prompt increase in proximal pressure followed by a progressive decline to lower hypertensive levels, revealing a significant role for the integrity of the neuroaxis in the maintenance of the aortic coarctation hypertension through the release of AVP. In conclusion, the important issue raised by this model of hypertension is the likelihood of a link between some vascular territory - probably renal - below the coarctation triggering the release of AVP, with this vasoconstrictor hormone participating with Ang II and the mechanical effect of aortic constriction in the acute aortic coarctation hypertension

  9. ATP sensitive K+channel subunits (Kir6.1, Kir6.2) are the candidate mediators regulating ameliorating effects of pulsed magnetic field on aortic contractility in diabetic rats.

    Science.gov (United States)

    Ocal, Isil; Yilmaz, Mehmet B; Kocaturk-Sel, Sabriye; Tufan, Turan; Erkoc, Mehmet A; Comertpay, Gamze; Oksuz, Hale; Barc, Esma D

    2018-02-15

    Diabetes mellitus is a metabolic disease that causes increased morbidity and mortality in developed and developing countries. With recent advancements in technology, alternative treatment methods have begun to be investigated in the world. This study aims to evaluate the effect of pulsed magnetic field (PMF) on vascular complications and contractile activities of aortic rings along with Kir6.1 and Kir6.2 subunit expressions of ATP-sensitive potassium channels (K ATP ) in aortas of controlled-diabetic and non-controlled diabetic rats. Controlled-diabetic and non-controlled diabetic adult male Wistar rats were exposed to PMF for a period of 6 weeks according to the PMF application protocol (1 h/day; intensity: 1.5 mT; consecutive frequency: 1, 10, 20, and 40 Hz). After PMF exposure, body weight and blood glucose levels were measured. Then, thoracic aorta tissue was extracted for relaxation-contraction and Kir6.1 and Kir6.2 expression experiments. Blood plasma glucose levels, body weight, and aortic ring contraction percentage decreased in controlled-diabetic rats but increased in non-controlled diabetic rats. PMF therapy repressed Kir6.1 mRNA expression in non-controlled diabetic rats but not in controlled diabetic rats. Conversely, Kir6.2 mRNA expressions were repressed both in controlled diabetic and non-controlled diabetic rats by PMF. Our findings suggest that the positive therapeutic effects of PMF may act through (K ATP ) subunits and may frequently occur in insulin-free conditions. Bioelectromagnetics. 2018;9999:XX-XX. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  10. Abdominal aortic injury in a child: intravenous digital subtraction angiogram (IVDSA) for the diagnosis of pediatric vascular trauma

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Gregory [Division of Interventional Radiology, Department of Diagnostic Imaging, Rhode Island Hospital, Brown Medical School, RI 02903, Providence (United States); Ibarra, Rodolfo; Ferral, Hector [Department of Radiology, University of Texas Health Science Center, San Antonio, TX (United States)

    2003-08-01

    Abdominal aortic injury due to trauma is a rare entity, especially in the pediatric population. We report a 6-year-old girl with partial transection of the abdominal aorta as a result of a motor vehicle accident. The diagnosis was made with IVDSA. The patient survived the injury. We discuss the imaging findings, mechanisms, and associated injuries of abdominal aortic trauma in children. (orig.)

  11. [Effect of premature birth on retinal vascular development in the neonatal rat].

    Science.gov (United States)

    Yang, Xiang-min; Li, Rong; Wang, Yu-sheng; Chu, Zhao-jie; Gao, Xiang

    2013-08-01

    To study the effects of premature birth on the development of rat retinal vasculature. Experimental study. Sixty pregnant Sprague-Dawley rats were divided into four groups: bacterial lipopolysaccharide-induced preterm group (LPS group), RU-486 induced preterm group (RP group), cesarean section induced preterm group (CP group), and the normal delivery rats as the control group. The weight of rats from each group was recorded until postnatal day 21. On postnatal day 4, 7, 10 and 14 (P4, P7, P10 and P14), the retina of right eye was dissected and whole-mounted. Each premature group was divided into two subgroups based on the number of rats in each litter, the small subgroup (6-8 rats per litter, group 1) and the large subgroup (14-18 rats per litter, group 2). The development of retinal vascularization process was observed on P4, P7 and P10 (n = 6).Independent t test, one-way ANOVA and LSD-t test were used to analyzed the results. The weight of premature rats in LPS, CP and RP groups was significantly lower than that in the normal group within postnatal 21 days (LSD-t test: all P premature rats have lower weight and much slower rate of early retinal vascularization, as compared with the normal rats. Furthermore, in the premature rats, the proportion of retinal vascularization in larger litters is less than that in smaller litters. These results indicate that premature birth and larger litter size have effects on the development of rat retinal vasculature.

  12. Efficacy of bosentan, a dual ETA and ETB endothelin receptor antagonist, in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.

    Science.gov (United States)

    Singh, Gurpreet; Sharma, Bhupesh; Jaggi, Amteshwar Singh; Singh, Nirmal

    2014-09-01

    The study was designed to investigate the efficacy of bosentan a dual endothelin (ETA and ETB) receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia. Diabetes was induced in rats by administration of a single dose (50mg/kg, i.p.) of streptozotocin (STZ). Drug treatment was started after 1 month of STZ administration and treatment was continued until the end of the study. Morris water maze (MWM) test was employed for testing spatial learning and memory. Endothelial function was measured on isolated aortic rings using student physiograph. Serum glucose, body weight, serum nitrite/nitrate, brain thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH) levels, and brain acetylcholinesterase activity were also tested. STZ treatment resulted in significant development of cognitive and vascular endothelial deficits, manifested in the terms of endothelial dysfunction, impairment of learning and memory, reduction in body weight and serum nitrite/nitrate levels along with increase in serum glucose, brain acetylcholinesterase activity, TBARS, and decreased GSH levels. Treatment of bosentan attenuated diabetes induced impairment of learning, memory, endothelial function, and various biochemical parameters. It may be concluded that bosentan has shown efficacy in STZ induced cognitive and vascular endothelial deficits. Thus, endothelin receptors can be considered as a potential pharmacological target for the management of experimental diabetes induced vascular endothelial dysfunction and associated dementia. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. L-carnitine attenuates cardiac remodelling rather than vascular remodelling in deoxycorticosterone acetate-salt hypertensive rats.

    Science.gov (United States)

    O'Brien, Daniel; Chunduri, Prasad; Iyer, Abishek; Brown, Lindsay

    2010-04-01

    L-carnitine is an important co-factor in fatty acid metabolism by mitochondria. This study has determined whether oral administration of L-carnitine prevents remodelling and the development of impaired cardiovascular function in deoxycorticosterone acetate (DOCA)-salt hypertensive rats (n = 6-12; #p carnitine (1.2% in food; 0.9 mg/g/day in DOCA-salt rats) decreased blood pressure (DOCA-salt 169 +/- 2; + L-carnitine 148 +/- 6# mmHg), decreased left ventricular wet weights (DOCA-salt 3.02 +/- 0.07; + L-carnitine 2.72 +/- 0.06# mg/g body-wt), decreased inflammatory cells in the replacement fibrotic areas, reduced left ventricular interstitial collagen content (DOCA-salt 14.4 +/- 0.2; + L-carnitine 8.7 +/- 0.5# % area), reduced diastolic stiffness constant (DOCA-salt 26.9 +/- 0.5; + L-carnitine 23.8 +/- 0.5# dimensionless) and decreased plasma malondialdehyde concentrations (DOCA-salt 26.9 +/- 0.8; + L-carnitine 21.2 +/- 0.4# micromol/l) without preventing endothelial dysfunction. L-carnitine attenuated the cardiac remodelling and improved cardiac function in DOCA-salt hypertension but produced minimal changes in aortic wall thickness and vascular function. This study suggests that the mitochondrial respiratory chain is a significant source of reactive oxygen species in the heart but less so in the vasculature in DOCA-salt rats, underlying the relatively selective cardiac responses to L-carnitine treatment.

  14. Clopidogrel, a platelet P2Y12 receptor inhibitor, reduces vascular inflammation and angiotensin II induced-abdominal aortic aneurysm progression.

    Directory of Open Access Journals (Sweden)

    Ou Liu

    Full Text Available Medial degeneration and inflammation are features of abdominal aortic aneurysms (AAAs. However, the early inflammatory event initiating aneurysm formation remains to be identified. Activated platelets release abundant proinflammatory cytokines and are involved in initial inflammation in various vascular diseases. We investigated the role of platelets in progression of AAA in vivo and in vitro. Histological studies of tissues of patients with AAA revealed that the number of platelets was increased in aneurysm sites along with the increased infiltration of T lymphocytes and augmented angiogenesis. In a murine model of AAA, apolipoprotein E-knockout mice infused with 1,000 ng/kg/min angiotensin II, treatment with clopidogrel, an inhibitor of platelets, significantly suppressed aneurysm formation (47% decrease, P<0.05. The clopidogrel also suppressed changes in aortic expansion, elastic lamina degradation and inflammatory cytokine expression. Moreover, the infiltration of macrophages and production of matrix metalloproteinases (MMPs were also significantly reduced by clopidogrel treatment. In vitro incubation of macrophages with isolated platelets stimulated MMP activity by 45%. These results demonstrate a critical role for platelets in vascular inflammation and AAA progression.

  15. Association of left subclavian artery coverage without revascularization and spinal cord ischemia in patients undergoing thoracic endovascular aortic repair: A Vascular Quality Initiative® analysis.

    Science.gov (United States)

    Teixeira, Pedro Gr; Woo, Karen; Beck, Adam W; Scali, Salvatore T; Weaver, Fred A

    2017-12-01

    Objectives Investigate the impact of left subclavian artery coverage without revascularization on spinal cord ischemia development in patients undergoing thoracic endovascular aortic repair. Methods The Vascular Quality Initiative thoracic endovascular aortic repair module (April 2011-July 2014) was analyzed. Patients undergoing left subclavian artery coverage were divided into two groups according to revascularization status. The association between left subclavian artery revascularization with the primary outcome of spinal cord ischemia and the secondary outcome of stroke was assessed with multivariable analysis adjusting for between-group baseline differences. Results The left subclavian artery was covered in 508 (24.6%) of the 2063 thoracic endovascular aortic repairs performed. Among patients with left subclavian artery coverage, 58.9% underwent revascularization. Spinal cord ischemia incidence was 12.1% in the group without revascularization compared to 8.5% in the group undergoing left subclavian artery revascularization (odds ratio (95%CI): 1.48(0.82-2.68), P = 0.189). Multivariable analysis adjustment identified an independent association between left subclavian artery coverage without revascularization and the incidence of spinal cord ischemia (adjusted odds ratio (95%CI): 2.29(1.03-5.14), P = 0.043). Although the incidence of stroke was also higher for the group with a covered and nonrevascularized left subclavian artery (12.1% versus 8.5%), this difference was not statistically significant after multivariable analysis (adjusted odds ratio (95%CI): 1.55(0.74-3.26), P = 0.244). Conclusion For patients undergoing left subclavian artery coverage during thoracic endovascular aortic repair, the addition of a revascularization procedure was associated with a significantly lower incidence of spinal cord ischemia.

  16. Nicotinamide and its metabolite N-methylnicotinamide increase skin vascular permeability in rats.

    Science.gov (United States)

    Pietrzak, L; Mogielnicki, A; Buczko, W

    2009-04-01

    It has been suggested that topically applied nicotinamide and its metabolite N-methylnicotinamide (NMN(+)) might be useful agents for treatment of dermatological disorders such as acne vulgaris and rosacea. This study aimed to find out if the mechanism of these therapeutic effects depends on their vascular effects, by investigating if nicotinamide and NMN(+) are able to influence vascular permeability of the vessels in the skin on the back of Wistar rats. A dose-dependent increase in vascular permeability was seen in rats treated intradermally with nicotinamide and NMN(+). Interestingly, a significantly stronger effect of NMN(+) compared with nicotinamide was evident. Increased vascular permeability in rats treated with 0.5% NMN(+) ointment was seen. Moreover, indomethacin, a cyclo-oxygenase 1 and 2 inhibitor and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, reduced the observed effects of nicotinamide and NMN(+). This study provides direct in vivo evidence that nicotinamide and its metabolite NMN(+) increase skin vascular permeability in rats by a mechanism that may involve NO and prostaglandins.

  17. The role of nitric oxide in the altered vascular reactivity of pregnancy in the rat.

    OpenAIRE

    Nathan, L; Cuevas, J; Chaudhuri, G

    1995-01-01

    1. Pregnancy is characterized by a decrease in systemic vascular resistance and a blunting of the angiotensin II (AII) pressor response. We studied the role of nitric oxide (NO) and prostanoids in these vascular changes of pregnancy in anaesthesized, ganglion blocked non-pregnant and pregnant rats. 2. Inhibition of NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME) led to an increase in mean arterial pressure (MAP) which was of a significantly greater magnitude in pregnant rats in la...

  18. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

    Directory of Open Access Journals (Sweden)

    Xue-ying Chang

    2017-01-01

    Full Text Available Background. This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d, 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS/p38 mitogen activated protein kinase (p38MAPK pathway was determined to explore the potential mechanism. Results. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA and creatinine levels, malonaldehyde (MDA content, and superoxide dismutase (SOD activity in serum and the increases of calcium and alkaline phosphatase (ALP activity in the aorta (P<0.05 and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Conclusions. Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

  19. Alterations in the vascular architecture of the dorsal root ganglia in a rat neuropathic pain model.

    Science.gov (United States)

    Kubícek, Lubos; Kopácik, Roman; Klusáková, Ilona; Dubový, Petr

    2010-04-20

    An alteration in the structural arrangement of blood vessels identified by RECA immunohistochemistry was studied in a rat L4 dorsal root ganglia (L4-DRG) neuropathic pain model. We compared a three-dimensional (3-D) reconstruction of the vascular architecture surrounding bodies of the primary sensory neurons in the L4-DRG of naïve rats with that of rats that had surgically undergone unilateral sciatic nerve ligature. Rhodamine-conjugated dextran (Fluoro-Ruby) was used for retrograde labelling of neurons, the axons of which had been injured by nerve ligature. In contrast to DRG from naïve rats and contralateral DRG from operated rats, an increased proportion of RECA+ vascular area and the appearance of nest-like arrangements of blood vessels around neuronal bodies with injured axons were observed in L4-DRG ipsilateral to the sciatic nerve ligature. Fractal analysis confirmed a higher degree of vascular branching, irregularity, and tortuosity in L4-DRG related with sciatic nerve injury. The results suggest that nerve injury induces changes in vascular architecture in associated DRG. Copyright 2010 Elsevier GmbH. All rights reserved.

  20. Effects of one resistance exercise session on vascular smooth muscle of hypertensive rats.

    Science.gov (United States)

    Silva, Tharciano Luiz Teixeira Braga da; Mota, Marcelo Mendonça; Fontes, Milene Tavares; Araújo, João Eliakim Dos Santos; Oliveira Carvalho, Vitor; Bonjardim, Leonardo Rigoldi; Santos, Márcio Roberto Viana

    2015-08-01

    Hypertension is a public health problem and increases the incidence of cardiovascular diseases. To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats. Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP). Rats treated with L-NAME showed an increase (p session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

  1. Nitric oxide-mediated changes in vascular reactivity in pregnancy in spontaneously hypertensive rats.

    OpenAIRE

    Chu, Z. M.; Beilin, L. J.

    1993-01-01

    1. To examine the mechanisms which may account for pregnancy-induced vasodilatation in spontaneously hypertensive rats (SHR), we have investigated the changes in vascular reactivity and the effects of endothelial nitric oxide (NO) inhibition in the in situ blood-perfused, mesenteric resistance vessels of 18-20 day pregnant SHR. The effects of NG-nitro-L-arginine (L-NOARG) were compared in pregnant and nonpregnant SHR and gestation matched normotensive Wistar-Kyoto (WKY) rats. 2. Intra-arteria...

  2. Effects of hypothyroidism on vascular /sup 125/I-albumin permeation and blood flow in rats

    Energy Technology Data Exchange (ETDEWEB)

    Tilton, R.G.; Pugliese, G.; Chang, K.; Speedy, A.; Province, M.A.; Kilo, C.; Williamson, J.R.

    1989-05-01

    Effects of hypothyroidism on vascular 125I-albumin permeation and on blood flow were assessed in multiple tissues of male Sprague-Dawley rats rendered hypothyroid by dietary supplementation with 0.5% (wt/wt) 2-thiouracil or by thyroidectomy. In both thiouracil-treated and thyroidectomized rats, body weights, kidney weight, arterial blood pressure, and pulse rate were decreased significantly v age-matched controls. After 10 to 12 weeks of thiouracil treatment, 125I-albumin permeation was increased significantly in the kidney, aorta, eye (anterior uvea, choroid, retina), skin, and new granulation tissue, remained unchanged in brain, sciatic nerve, and heart, and was decreased in forelimb skeletal muscle. A similar pattern was observed in thyroidectomized rats, except that increases in 125I-albumin permeation for all tissues were smaller than those observed in thiouracil-treated rats, and 125I-albumin permeation in retina did not differ from controls. In both thiouracil-treated and thyroidectomized rats, changes in blood flow (assessed with 15-microns, 85Sr-labeled microspheres) relative to the decrease in arterial blood pressure were indicative of a decrease in regional vascular resistance except in the choroid and in the kidney, in which vascular resistance was increased significantly. Glomerular filtration rate was decreased, but filtration fraction and urinary excretion of albumin remained unchanged by thiouracil treatment and thyroidectomy. These results indicate that vascular hemodynamics and endothelial cell barrier functional integrity are modulated in many different tissues by the thyroid. In view of the correspondence of hypothyroid- and diabetes-induced vascular permeability changes, these results raise the possibility that altered thyroid function in diabetes may play a role in the pathogenesis of diabetic vascular disease.

  3. Step training in a rat model for complex aneurysmal vascular microsurgery

    Directory of Open Access Journals (Sweden)

    Martin Dan

    2015-12-01

    Full Text Available Introduction: Microsurgery training is a key step for the young neurosurgeons. Both in vascular and peripheral nerve pathology, microsurgical techniques are useful tools for the proper treatment. Many training models have been described, including ex vivo (chicken wings and in vivo (rat, rabbit ones. Complex microsurgery training include termino-terminal vessel anastomosis and nerve repair. The aim of this study was to describe a reproducible complex microsurgery training model in rats. Materials and methods: The experimental animals were Brown Norway male rats between 10-16 weeks (average 13 and weighing between 250-400g (average 320g. We performed n=10 rat hind limb replantations. The surgical steps and preoperative management are carefully described. We evaluated the vascular patency by clinical assessment-color, temperature, capillary refill. The rats were daily inspected for any signs of infections. The nerve regeneration was assessed by foot print method. Results: There were no case of vascular compromise or autophagia. All rats had long term survival (>90 days. The nerve regeneration was clinically completed at 6 months postoperative. The mean operative time was 183 minutes, and ischemia time was 25 minutes.

  4. Surgical Anatomy and Microvascular Surgical Technique Relevant to Experimental Renal Transplant in Rat Employing Aortic and Inferior Venacaval Conduits.

    Science.gov (United States)

    Shrestha, Badri Man; Haylor, John

    2017-11-15

    Rat models of renal transplant are used to investigate immunologic processes and responses to therapeutic agents before their translation into routine clinical practice. In this study, we have described details of rat surgical anatomy and our experiences with the microvascular surgical technique relevant to renal transplant by employing donor inferior vena cava and aortic conduits. For this study, 175 rats (151 Lewis and 24 Fisher) were used to establish the Fisher-Lewis rat model of chronic allograft injury at our institution. Anatomic and technical details were recorded during the period of training and establishment of the model. A final group of 12 transplanted rats were studied for an average duration of 51 weeks for the Lewis-to-Lewis isografts (5 rats) and 42 weeks for the Fisher-to-Lewis allografts (7 rats). Functional measurements and histology confirmed the diagnosis of chronic allograft injury. Mastering the anatomic details and microvascular surgical techniques can lead to the successful establishment of an experimental renal transplant model.

  5. Genistein Prevents Hyperglycemia-Induced Monocyte Adhesion to Human Aortic Endothelial Cells through Preservation of the cAMP Signaling Pathway and Ameliorates Vascular Inflammation in Obese Diabetic Mice123

    OpenAIRE

    Babu, Pon Velayutham Anandh; Si, Hongwei; Fu, Zhuo; Zhen, Wei; Liu, Dongmin

    2012-01-01

    Hyperglycemia-induced vascular inflammation resulting in the enhanced monocyte-endothelial cell (EC) interaction is the key event in the pathogenesis of atherosclerosis in diabetes. Here, we investigated the effect of isoflavone genistein on hyperglycemia-stimulated vascular inflammation. Human aortic EC (HAEC) were pretreated with genistein before the addition of high glucose (HG; 25 mmol/L) for 48 h. Genistein at a physiological concentration (0.1 μmol/L) significantly inhibited HG-induced ...

  6. Mathematical Modeling of Neuro-Vascular Coupling in Rat Cerebellum

    DEFF Research Database (Denmark)

    Rasmussen, Tina

    measured field potential is used as an indicator of neuronal activity, and the cortical blood flow is measured by means of laser-Doppler flowmetry. Using system identification methods, these measurements have been used to construct and validate parametric mathematical models of the neuro-vascular system....... Mathematical arguments as well as hypotheses about the physiological system have been used to construct the models.......Activity in the neurons called climbing fibers causes blood flow changes. But the physiological mechanisms which mediate the coupling are not well understood. This PhD thesis investigates the mechanisms of neuro-vascular coupling by means of mathematical methods. In experiments, the extracellularly...

  7. Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway.

    Science.gov (United States)

    Zhao, Jing; Liu, Ge-Li; Wei, Ying; Jiang, Li-Hong; Bao, Peng-Li; Yang, Qing-Yan

    2016-09-01

    The aim of the present study was to investigate the effect of testosterone on glucolipid metabolism and vascular injury in male rats, and examine the underlying molecular mechanisms. A total of 40 male Sprague-Dawley rats were divided into a control group (n=10), high-fat-diet + castration group (n=10), high‑fat‑diet + castration + low dose testosterone group (n=10), and high-fat-diet + castration + high dose testosterone group (n=10). Hematoxylin and eosin staining was performed to evaluate the morphology of the thoracic aortic tissues. Immunohistochemical staining was used to detect biomarkers of the phosphoinositide 3‑kinase (PI3K) signaling pathway. The mRNA and protein expression levels of PI3K, AKT, insulin receptor substrate‑1 (IRS‑1), glucose transporter type 4 (GLUT‑4), nuclear factor (NF)‑κB and tumor necrosis factor (TNF)‑α in the aortas were determined using quantitative polymerase chain reaction and Western blot analyses, respectively. Apoptosis in the aortic tissues was detected using a TUNEL assay. Castration induced apoptosis in the animals fed a high‑fat‑diet, whereas low dose testosterone replacement ameliorated the apoptosis in the aorta. However, the levels of apoptosis was more severe following high‑dose testosterone treatment. Low‑dose testosterone induced upregulation in the levels of IRS‑1, AKT, GLUT‑4 protein, NF‑κB, TNF‑α and PI3K, compared with those in the animals fed a high‑fat diet following castration. A high dose of testosterone resulted in a significant decrease in the levels of IRS‑1, AKT, GLUT‑4, NF‑κB, TNF‑α and PI3K. Compared with the rats in the high‑fat diet + castration group, a low dose of testosterone induced upregulation in the mRNA levels of IRS‑1, AKT and GLUT‑4, and downregulation of the mRNA levels of NF‑κB, TNF‑α and PI3K. A high dose of testosterone resulted in a significant decrease in the levels of IRS‑1, AKT and GLUT‑4, and marked

  8. Modeling neuro-vascular coupling in rat cerebellum

    DEFF Research Database (Denmark)

    Rasmussen, Tina; Holstein-Rathlou, Niels-Henrik; Lauritzen, Martin

    2009-01-01

    We investigated the quantitative relation between neuronal activity and blood flow by means of a general parametric mathematical model which described the neuro-vascular system as being dynamic, linear, time-invariant, and subjected to additive noise. The model was constructed from measurements b...

  9. Vascular smooth muscle function of renal glomerular and interlobar arteries predicts renal damage in rats

    NARCIS (Netherlands)

    Vavrinec, Peter; Henning, Robert H.; Goris, Maaike; Vavrincova-Yaghi, Diana; Buikema, Hendrik; van Dokkum, Richard P. E.

    2012-01-01

    Vavrinec P, Henning RH, Goris M, Vavrincova-Yaghi D, Buikema H, van Dokkum RP. Vascular smooth muscle function of renal glomerular and interlobar arteries predicts renal damage in rats. Am J Physiol Renal Physiol 303: F1187-F1195, 2012. First published July 11, 2012;

  10. Physiologic Responses to Infrarenal Aortic Cross-Clamping during Laparoscopic or Conventional Vascular Surgery in Experimental Animal Model: Comparative Study

    Directory of Open Access Journals (Sweden)

    María F. Martín-Cancho

    2008-01-01

    Full Text Available The aim of this study was to compare the hemodynamic and ventilatory effects of prolonged infrarenal aortic cross-clamping in pigs undergoing either laparotomy or laparoscopy. 18 pigs were used for this study. Infrarenal aortic crossclamping was performed for 60 minutes in groups I (laparotomy, n=6 and II (laparoscopy, n=6. Group III (laparoscopy, n=6 underwent a 120-minute long pneumoperitoneum in absence of aortic clamping (sham group. Ventilatory and hemodynamic parameters and renal function were serially determined in all groups. A significant decrease in pH and significant increase in PaCO2 were observed in group II, whereas no changes in these parameters were seen in group I and III. All variables returned to values similar to baseline in groups I and II 60 minutes after declamping. A significant increase in renal resistive index was evidenced during laparoscopy, with significantly higher values seen in Group II. Thus a synergic effect of pneumoperitoneum and aortic cross-clamping was seen in this study. These two factors together cause decreased renal perfusion and acidosis, thus negatively affecting the patient's general state during this type of surgery.

  11. Supravalvular aortic stenosis associated to infectious endocarditis and cerebral vascular disease in a patient with Williams-Beuren Syndrome.

    Science.gov (United States)

    De Rubens Figueroa, Jesús; Marhx, Alfonso; López Terrazas, Javier; Palacios Macedo, Alexis

    2015-01-01

    The Williams-Beuren syndrome is a rare genetic disease characterized by: (a) typical facial features; (b) psychomotor retardation with a specific neurocognitive profile; (c) cardiovascular condition and (d) likely transient hypocalcemia in infancy. The objective of this study was to describe the clinic evolution and diagnosis of patient with this syndrome that was associated with endocarditis caused by Streptococcus parasanguis in the ascending aorta and an aneurism located in the fronto-temporal area, which produced a parenchymal hematoma in the left lobe, and subarachnoid hemorrhage. He was treated with ceftriaxone and dicloxacillin. Then we proceeded to correct the aneurysm and perform vegetation resection in aortic arteries with supravalvular aortic stenosis correction. The evolution after one year has been favorable and is currently without neurologic sequelae. A 5-year-old male patient presented a diagnosis of supravalvular aortic stenosis. After cardiac catheterization was performed, he presented a fever and right side paresis. The echocardiogram showed multiple vegetations in the ascendant aortic arch and the supraortic arteries. The blood cultures reported S. parasanguis. The magnetic resonance showed a subarachnoid hemorrhage with an aneurysm and a hematoma. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  12. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats.

    Science.gov (United States)

    Li, Peng; Huang, Pei-Pei; Yang, Yun; Liu, Chi; Lu, Yan; Wang, Fang; Sun, Wei; Kong, Xiang-Qing

    2017-01-01

    Li P, Huang P, Yang Y, Liu C, Lu Y, Wang F, Sun W, Kong X. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats. J Appl Physiol 122: 121-129, 2017. First published October 14, 2016; doi:10.1152/japplphysiol.01019.2015-Sympathetic activity is enhanced in patients with essential or secondary hypertension, as well as in various hypertensive animal models. Therapeutic targeting of sympathetic activation is considered an effective antihypertensive strategy. We hypothesized that renal sympathetic denervation (RSD) attenuates hypertension and improves vascular remodeling and renal disease in the 2-kidney, 1-clip (2K1C) rat model. Rats underwent 2K1C modeling or sham surgery; then rats underwent RSD or sham surgery 4 wk later, thus resulting in four groups (normotensive-sham, normotensive-RSD, 2K1C-sham, and 2K1C-RSD). Norepinephrine was measured by ELISA. Echocardiography was used to assess heart function. Fibrosis and apoptosis were assessed by Masson and TUNEL staining. Changes in mean arterial blood pressure in response to hexamethonium and plasma norepinephrine levels were used to evaluate basal sympathetic nerve activity. The 2K1C modeling success rate was 86.8%. RSD reversed the elevated systolic blood pressure induced by 2K1C, but had no effect on body weight. Compared with rats in the 2K1C-sham group, rats in the 2K1C-RSD group showed lower left ventricular mass/body weight ratio, interventricular septal thickness in diastole, left ventricular end-systolic diameter, and left ventricular posterior wall thickness in systole, whereas fractional shortening and ejection fraction were higher. Right kidney apoptosis and left kidney hypertrophy were not changed by RSD. Arterial fibrosis was lower in animals in the 2K1C-RSD group compared with those in the 2K1C-sham group. RSD reduced plasma norepinephrine and basal sympathetic activity in rats in the 2K1C-RSD group compared with rats in the 2K1C-sham group. These

  13. Ethyl Pyruvate Prevents Methyglyoxal-Induced Retinal Vascular Injury in Rats

    Directory of Open Access Journals (Sweden)

    Junghyun Kim

    2013-01-01

    Full Text Available Pyruvate is an endogenous antioxidant substance. The aim of this study was to investigate the protective effects of ethyl pyruvate (EP on retinal vascular injury in diabetic retinopathy. To investigate the protective effect of EP on vascular cell apoptosis and blood-retinal barrier (BRB breakage, we have used intravitreally methylglyoxal-(MGO- injected rat eyes. Apoptosis of the retinal vascular cell that was stimulated by the intravitreal injection of MGO was evidently attenuated by the EP treatment. EP exerts inhibitory effect on MGO-induced vascular cell apoptosis by blocking oxidative injury. In addition, EP treatment prevented MGO-induced BRB breakage and the degradation of occludin, an important tight junction protein. These observations suggest that EP acts through an antioxidant mechanism to protect against oxidative stress-induced apoptosis in retinal vessels.

  14. Sida rhomboidea.Roxb aqueous extract down-regulates in vivo expression of vascular cell adhesion molecules in atherogenic rats and inhibits in vitro macrophage differentiation and foam cell formation.

    Science.gov (United States)

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Salunke, Sunita P; Devkar, Ranjitsinh V; Ramachandran, A V

    2012-10-01

    The present study evaluates efficacy of Sida rhomboidea.Roxb (SR) leaves extract in ameliorating experimental atherosclerosis using in vitro and in vivo experimental models. Atherogenic (ATH) diet fed rats recorded significant increment in the serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), very LDL (VLDL), autoantibody against oxidized LDL (Ox-LDL), markers of LDL oxidation and decrement in high-density lipoprotein (HDL) along with increment in aortic TC and TG. The ex vivo LDL oxidation assay revealed an increased susceptibility of LDL isolated from ATH rats to undergo copper mediated oxidation. These set of changes were minimized by simultaneous co-supplementation of SR extract to ATH diet fed rats. Histopathology of aorta and immunolocalization studies recorded pronounced atheromatous plaque formation, vascular calcification, significant elastin derangements and higher expression of macrophage surface marker (F4/80), vascular cell adhesion molecule-1 (VCAM-1) and p-selectin in ATH rats. Whereas, ATH+SR rats depicted minimal evidence of atheromatous plaque formation, calcium deposition, distortion/defragmentation of elastin and accumulation of macrophages along with lowered expression of VCAM-1 and P-selectin compared to ATH rats. Further, monocyte to macrophage differentiation and in vitro foam cell formation were significantly attenuated in presence of SR extract. In conclusion, SR extract has the potency of controlling experimental atherosclerosis and can be used as promising herbal supplement in combating atherosclerosis.

  15. Preventive effect of Eucommia leaf extract on aortic media hypertrophy in Wistar-Kyoto rats fed a high-fat diet.

    Science.gov (United States)

    Hosoo, Shingo; Koyama, Masahiro; Watanabe, Akira; Ishida, Ryuya; Hirata, Tetsuya; Yamaguchi, Yasuyo; Yamasaki, Hiroo; Wada, Keiji; Higashi, Yukihito; Nakamura, Kozo

    2017-06-01

    Eucommia ulmoides Oliver leaf extract (ELE) has been shown to have anti-hypertensive and anti-obesity effects in rats that are fed a high-fat diet (HFD). To explore the effects of chronic administration of ELE on body weight, blood pressure and aortic media thickness, 7-week-old male Wistar-Kyoto (WKY) rats were orally administered a normal diet, a 30% HFD, or a 5% ELE plus HFD ad libitum for 10 weeks. The HFD treatment caused mild obesity and hypertension in the normotensive rats, while rats receiving both ELE and the HFD had significantly lower body weights, less visceral and perirenal fat, lower blood pressure and thinner aortic media than the control rats receiving the HFD only. The plasma adiponectin/leptin ratio also improved in ELE-treated rats. Although plasma leptin levels were elevated in all HFD rats, adiponectin levels increased only in the ELE-treated rats. Anti-hypertensive and anti-obesity effects may be caused by the geniposidic acid (GEA) and/or asperuloside present in ELE. These findings suggest that chronic ELE administration prevents aortic media hypertrophy in early-stage obesity with hypertension. Long-term administration of ELE might inhibit the development of arteriosclerosis.

  16. Angiopoietins regulate vascular reactivity after haemorrhagic shock in rats through the Tie2-nitric oxide pathway.

    Science.gov (United States)

    Xu, Jing; Lan, Dan; Li, Tao; Yang, Guangming; Liu, Liangming

    2012-11-01

    Vascular reactivity shows biphasic changes after severe trauma or shock. Our aim was to elucidate the mechanisms of biphasic-changed vascular reactivity after haemorrhagic shock by observing the regulation of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) on it. Haemorrhagic-shock Sprague-Dawley rats, hypoxia-treated superior mesenteric arteries (SMAs) with intact endothelia, and a cell mixture of vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) were adopted to evaluate the regulatory effects of Ang-1 and Ang-2 on vascular reactivity and their relationship to Tie2 (receptor tyrosine kinase)-Akt-endothelial nitric oxide synthase (eNOS) and Tie2-extracellular signal-regulated kinase (Erk)-inducible nitric oxide synthase (iNOS) signal pathways. Ang-1 expression, Tie2 phosphorylation, and nitric oxide (NO) release were increased at early shock. Exogenous Ang-1 maintained the vascular reactivity of SMAs after early hypoxia. Tie2-blocking antibody and the antagonists of Akt and eNOS antagonized Ang-1-induced maintenance in vascular reactivity and a slight release in NO at the early stage of shock. Ang-2 expression, Tie2 phosphorylation, and NO release were greatly increased at late shock, but exogenous Ang-2 further decreased the vascular reactivity of SMAs after late hypoxia. Tie2-blocking antibody and the antagonists of Erk and iNOS andtagonized the Ang-2-induced decrease in vascular reactivity and a large release of NO at the late stage of shock. Ang-1 and Ang-2 participated in the regulation of vascular reactivity after haemorrhagic shock. Ang-1 was mainly responsible for the hyperreactivity at early shock through the Tie2-Akt-eNOS pathway and an appropriate amount of NO release. Ang-2 was mainly responsible for the hyporeactivity at late shock through the Tie2-Erk-iNOS pathway and the release of a large amount of NO.

  17. miR-503 inhibits platelet-derived growth factor-induced human aortic vascular smooth muscle cell proliferation and migration through targeting the insulin receptor.

    Science.gov (United States)

    Bi, Rui; Ding, Fangbao; He, Yi; Jiang, Lianyong; Jiang, Zhaolei; Mei, Ju; Liu, Hao

    2016-12-01

    Abnormal proliferation and migration of vascular smooth muscle cells (VSMC) is a common feature of disease progression in atherosclerosis. Here, we investigated the potential role of miR-503 in platelet-derived growth factor (PDGF)-induced proliferation and migration of human aortic smooth muscle cells and the underlying mechanisms of action. miR-503 expression was significantly downregulated in a dose- and time-dependent manner following PDGF treatment. Introduction of miR-503 mimics into cultured SMCs significantly attenuated cell proliferation and migration induced by PDGF. Bioinformatics analyses revealed that the insulin receptor (INSR) is a target candidate of miR-503. miR-503 suppressed luciferase activity driven by a vector containing the 3'-untranslated region of INSR in a sequence-specific manner. Downregulation of INSR appeared critical for miR-503-mediated inhibitory effects on PDGF-induced cell proliferation and migration in human aortic SMCs. Based on the collective data, we suggest a novel role of miR-503 as a regulator of VSMC proliferation and migration through modulating INSR. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Assessment of ventriculo-vascular properties in repaired coarctation using cardiac magnetic resonance-derived aortic, left atrial and left ventricular strain

    Energy Technology Data Exchange (ETDEWEB)

    Shang, Quanliang [University of Nebraska College of Medicine and Children' s Hospital and Medical Center, Division of Pediatric Cardiology, Omaha, NE (United States); Central South University, Department of Radiology, Second Xiangya Hospital, Changsha, Hunan Province (China); Sarikouch, Samir; Beerbaum, Philipp [Hannover Medical School, Hannover (Germany); Patel, Shivani; Danford, David A.; Kutty, Shelby [University of Nebraska College of Medicine and Children' s Hospital and Medical Center, Division of Pediatric Cardiology, Omaha, NE (United States); Schuster, Andreas [Department of Cardiology and Pneumonology, Georg-August-University and German Center for Cardiovascular Research (DZHK, Partner Site), Goettingen (Germany); Steinmetz, Michael [Department of Pediatric Cardiology, Georg-August-University and German Center for Cardiovascular Research (DZHK, Partner Site), Goettingen (Germany); Ou, Phalla [University Paris Diderot, Department of Radiology, Hospital Bichat, APHP, Paris (France)

    2017-01-15

    In patients with repaired coarctation of aorta (CoA), we assessed ventriculo-vascular characteristics using CMR-derived aortic area strain (AAS), left atrial (LA) and left ventricular (LV) longitudinal and circumferential strain (LS, CS). Seventy-five subjects including 50 with repaired CoA divided into hypertensive (n = 25), normotensive (n = 25) and 25 controls were studied. AAS was measured at 3 levels: ascending aorta, proximal descending and descending aorta. LA and LV LS were measured using CMR-feature tracking. LA and LV end-diastolic volumes, ejection fraction (EF) and mass were measured. Mean patient age was 19.7 ± 6.7 and controls 23 ± 15 (years). All strains (LA, LV, ascending and descending aortic) were lower in CoA subgroups compared to controls except the AAS at diaphragm, which was not different. Comparisons between hypertensive and normotensive CoA showed no differences in LV mass, LV volumetric indices, and LA and LV strain indices; however, ascending AAS was lower in hypertensive subgroup (p = 0.02). Ascending AAS was correlated with LV mass (r = -0.4, p = 0.005), LVEF (r = -0.4, p = 0.004), systolic blood pressure (r = -0.5, p = 0.0001) and LVLS (r = 0.5, p = 0.001). Ascending AAS correlated with LV mass, EF and LVLS. In hypertensive CoA, ascending AAS was reduced compared to normotensive CoA and controls, indicating vascular remodelling differences influenced by ongoing hypertension. (orig.)

  19. Vascular responsiveness in isolated perfused kidneys of diabetic hypertensive rats

    NARCIS (Netherlands)

    Beenen, O. H.; Mathy, M. J.; Pfaffendorf, M.; van Zwieten, P. A.

    1996-01-01

    The aim of this study was to investigate whether diabetes and hypertension cause additive effects in the responses to various vasoconstrictor and vasodilator agents, in isolated perfused kidneys obtained from streptozotocin (STZ)-diabetic Wistar-Kyoto (WKY) rats and from diabetic spontaneously

  20. Preserved vascular reactivity of rat renal arteries after cold storage.

    NARCIS (Netherlands)

    Bartels-Stringer, M.; Terlunen, L.; Siero, H.L.M.; Russel, F.G.M.; Smits, P.; Kramers, C.

    2004-01-01

    In cultured renal tubular cells hypothermia results in cell damage caused by iron-dependent formation of reactive oxygen species. It is unknown whether cold preservation affects function of renal vessels. Rat renal arcuate arteries were stored in a physiological salt solution at 4 degrees C for 24h

  1. White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies.

    Science.gov (United States)

    Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli

    2017-02-01

    We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p < 0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age-matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 expression around blood vessels. MMI-induced glymphatic dysfunction with delayed cerebrospinal fluid penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases Aquaporin-4 and induces glymphatic dysfunction which may play an important role in MMI-induced axonal/WM damage and cognitive deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The retardation of vasculopathy induced by attenuation of insulin resistance in the corpulent JCR:LA-cp rat is reflected by decreased vascular smooth muscle cell proliferation in vivo.

    Science.gov (United States)

    Absher, P M; Schneider, D J; Baldor, L C; Russell, J C; Sobel, B E

    1999-04-01

    Proliferation in vivo of vascular smooth muscle cells occurs early in the course of atherosclerosis. Cultured smooth muscle cells (SMCs) explanted from aortas of JCR:LA-cp corpulent rats known to exhibit metabolic derangements and insulin resistance typical of type II diabetes early in life and to develop atherosclerosis later in life exhibit increased proliferation compared with SMCs from lean, normal rats. Vascular smooth muscle proliferation in vitro was found to be positively and significantly correlated with plasma insulin levels in vivo. Proliferation of aortic SMCs from JCR:LA-cp cp/cp corpulent rats cultured in vitro exhibited increased proliferation in the presence of exogenous insulin. Exercise and diet, selected as interventions designed to ameliorate the insulin resistance and hyperinsulinemia in the JCR:LA-cp cp/cp rat, effectively lowered blood insulin levels and decreased subsequent proliferation in vitro of aortic SMCs explanted from these animals. The results indicate that assessment of proliferation of vascular smooth muscle cells ex vivo may provide insight into the presence and severity of atherogenicity in association with insulin resistance in diverse species under diverse circumstances. Accordingly, with appropriate controls, it may be possible to use SMC proliferation ex vivo as a marker of the extent to which an intervention such as administration of insulin sensitizers to experimental animals and human subjects results in a change in behavior of vessel wall elements potentially indicative of amelioration of atherogenicity and detectable as judged from reduced proliferative rates of the cells ex vivo when they have been harvested from vessels exposed to a milieu in which insulin resistance has been attenuated.

  3. Aortic and carotid arterial stiffness and epigenetic regulator gene expression changes precede blood pressure rise in stroke-prone Dahl salt-sensitive hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Victoria L Herrera

    Full Text Available Multiple clinical studies show that arterial stiffness, measured as pulse wave velocity (PWV, precedes hypertension and is an independent predictor of hypertension end organ diseases including stroke, cardiovascular disease and chronic kidney disease. Risk factor studies for arterial stiffness implicate age, hypertension and sodium. However, causal mechanisms linking risk factor to arterial stiffness remain to be elucidated. Here, we studied the causal relationship of arterial stiffness and hypertension in the Na-induced, stroke-prone Dahl salt-sensitive (S hypertensive rat model, and analyzed putative molecular mechanisms. Stroke-prone and non-stroke-prone male and female rats were studied at 3- and 6-weeks of age for arterial stiffness (PWV, strain, blood pressure, vessel wall histology, and gene expression changes. Studies showed that increased left carotid and aortic arterial stiffness preceded hypertension, pulse pressure widening, and structural wall changes at the 6-week time-point. Instead, differential gene induction was detected implicating molecular-functional changes in extracellular matrix (ECM structural constituents, modifiers, cell adhesion, and matricellular proteins, as well as in endothelial function, apoptosis balance, and epigenetic regulators. Immunostaining testing histone modifiers Ep300, HDAC3, and PRMT5 levels confirmed carotid artery-upregulation in all three layers: endothelial, smooth muscle and adventitial cells. Our study recapitulates observations in humans that given salt-sensitivity, increased Na-intake induced arterial stiffness before hypertension, increased pulse pressure, and structural vessel wall changes. Differential gene expression changes associated with arterial stiffness suggest a molecular mechanism linking sodium to full-vessel wall response affecting gene-networks involved in vascular ECM structure-function, apoptosis balance, and epigenetic regulation.

  4. Dietary magnesium supplementation prevents and reverses vascular and soft tissue calcifications in uremic rats.

    Science.gov (United States)

    Diaz-Tocados, Juan M; Peralta-Ramirez, Alan; Rodríguez-Ortiz, María E; Raya, Ana I; Lopez, Ignacio; Pineda, Carmen; Herencia, Carmen; Montes de Oca, Addy; Vergara, Noemi; Steppan, Sonja; Pendon-Ruiz de Mier, M Victoria; Buendía, Paula; Carmona, Andrés; Carracedo, Julia; Alcalá-Díaz, Juan F; Frazao, Joao; Martínez-Moreno, Julio M; Canalejo, Antonio; Felsenfeld, Arnold; Rodriguez, Mariano; Aguilera-Tejero, Escolástico; Almadén, Yolanda; Muñoz-Castañeda, Juan R

    2017-11-01

    Although magnesium has been shown to prevent vascular calcification in vitro, controlled in vivo studies in uremic animal models are limited. To determine whether dietary magnesium supplementation protects against the development of vascular calcification, 5/6 nephrectomized Wistar rats were fed diets with different magnesium content increasing from 0.1 to 1.1%. In one study we analyzed bone specimens from rats fed 0.1%, 0.3%, and 0.6% magnesium diets, and in another study we evaluated the effect of intraperitoneal magnesium on vascular calcification in 5/6 nephrectomized rats. The effects of magnesium on established vascular calcification were also evaluated in uremic rats fed on diets with either normal (0.1%) or moderately increased magnesium (0.6%) content. The increase in dietary magnesium resulted in a marked reduction in vascular calcification, together with improved mineral metabolism and renal function. Moderately elevated dietary magnesium (0.3%), but not high dietary magnesium (0.6%), improved bone homeostasis as compared to basal dietary magnesium (0.1%). Results of our study also suggested that the protective effect of magnesium on vascular calcification was not limited to its action as an intestinal phosphate binder since magnesium administered intraperitoneally also decreased vascular calcification. Oral magnesium supplementation also reduced blood pressure in uremic rats, and in vitro medium magnesium decreased BMP-2 and p65-NF-κB in TNF-α-treated human umbilical vein endothelial cells. Finally, in uremic rats with established vascular calcification, increasing dietary magnesium from 0.1% magnesium to 0.6% reduced the mortality rate from 52% to 28%, which was associated with reduced vascular calcification. Thus, increasing dietary magnesium reduced both vascular calcification and mortality in uremic rats. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  5. Effects of Urotensin II and Its Specific Receptor Antagonist Urantide on Rat Vascular Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Juan Zhao

    2013-05-01

    Full Text Available We investigated the effects of urantide, a receptor antagonist of urotensin II (U-II, on the expression of U-II and its receptor GPR14 in rat vascular smooth muscle cells. Vascular smooth muscle cells from rat thoracic aorta were cultured by explant method. Subjects in this experiment were divided into eight groups: normal control group (group C, U-II group (group M, positive control group (Flu group and urantide-treated groups (10-10, 10-9, 10-8, 10-7 and 10-6 mol/L. Cultured vascular smooth muscle cells in vitro were studied by immunocytochemistry, biochemistry, and flow cytometry. U-II (10-8 mol/L promoted the proliferation of vascular smooth muscle cells at each time point, influenced cell cycle, increased proliferation index and S-phase cell fraction, and dramatically promoted the expression of U-II and GPR14. In the concentration range from 10-10 to 10-6 mol/L, urantide dramatically inhibited the proliferation of vascular smooth muscle cells and the protein expression of U-II and GPR14, especially at a concentration of 10-6 mol/L. U-II, binding with its receptor GPR14, promotes vascular smooth muscle cells proliferation and migration, which can be inhibited by urantide. This study provides an evidence for understanding the effects of U-II and its receptor GPR14 on vascular smooth muscle cells.

  6. Cyclic Mechanical Stretch Up-regulates Hepatoma-Derived Growth Factor Expression in Cultured Rat Aortic Smooth Muscle Cells.

    Science.gov (United States)

    Kao, Ying-Hsien; Chen, Po-Han; Sun, Cheuk-Kwan; Chang, Yo-Chen; Lin, Yu-Chun; Tsai, Ming-Shian; Lee, Po-Huang; Cheng, Cheng-I

    2018-02-21

    Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. This study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uni-axial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 hours of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and PCNA, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced TNF-a, whereas RhoA/ROCK inhibition significantly blunted the IL-6 production and HDGF over-expression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration. ©2018 The Author(s).

  7. Relaxation of rabbit corpus cavernosum smooth muscle and aortic vascular endothelium induced by new nitric oxide donor substances of the nitrosyl-ruthenium complex

    Directory of Open Access Journals (Sweden)

    Joao B. G. Cerqueira

    2008-10-01

    Full Text Available INTRODUCTION: Endothelial dysfunction characterized by endogenous nitric oxide (NO deficiency made 56% of patients affected with erectile dysfunction decline treatment with PDE-5 inhibitors. New forms of treatment are currently being developed for this group of patients. MATERIALS AND METHODS: The study compared the effect of sodium nitroprusside (SNP and two substances of the nitrosyl-ruthenium complex, cis-[Ru(bpy2(SO3(NO]PF-6-9 ("FONO1” and trans-[Ru(NH34(caffeine(NO]C13 ("LLNO1” on relaxation of rabbit corpus cavernosum smooth muscle and aortic vascular endothelium. The samples were immersed in isolated baths and precontracted with 0.1 µM phenylephrine (PE and the corresponding relaxation concentration/response curves were plotted. In order to investigate the relaxation mechanisms involved, 100 µM ODQ (a soluble guanylate cyclase-specific inhibitor, 3 µM or 10 µM oxyhemoglobin (an extracellular NO scavenger or 1 mM L-cysteine (a nitrosyl anion-specific scavenger was added to the samples. RESULTS: All the NO donors tested produced a significant level of relaxation in the vascular endothelium. In corpus cavernosum samples, FONO1 produced no significant effect, but LLNO1 and SNP induced dose-dependent relaxation with comparable potency (pEC50 = 6.14 ± 0.08 and 6.4 ± 0.14, respectively and maximum effect (Emax = 82% vs. 100%, respectively. All NO donors were found to activate soluble guanylate cyclase, since the addition of the corresponding inhibitor (100 µM ODQ completely neutralized the relaxation effect observed. The addition of oxyhemoglobin reduced the relaxation effect, but did not inhibit it completely. In aortic vascular endothelium 3 µM oxyhemoglobin decreased the relaxation effect by 26% on the average, while 10 µM oxyhemoglobin reduced it by over 52%. The addition of 100 µM L-cysteine produced no significant inhibiting effect. CONCLUSIONS: These results suggest that LLNO1 and FONO1 are potent vasodilators. LLNO1 was

  8. Rosmarinic Acid Alleviates the Endothelial Dysfunction Induced by Hydrogen Peroxide in Rat Aortic Rings via Activation of AMPK.

    Science.gov (United States)

    Zhou, Hui; Fu, Baocai; Xu, Bo; Mi, Xiangquan; Li, Gang; Ma, Chengjun; Xie, Jianxin; Li, Ji; Wang, Zhenhua

    2017-01-01

    Endothelial dysfunction is the key player in the development and progression of vascular events. Oxidative stress is involved in endothelial injury. Rosmarinic acid (RA) is a natural polyphenol with antioxidative, antiapoptotic, and anti-inflammatory properties. The present study investigates the protective effect of RA on endothelial dysfunction induced by hydrogen peroxide (H2O2). Compared with endothelium-denuded aortic rings, the endothelium significantly alleviated the decrease of vasoconstrictive reactivity to PE and KCl induced by H2O2. H2O2 pretreatment significantly injured the vasodilative reactivity to ACh in endothelium-intact aortic rings in a concentration-dependent manner. RA individual pretreatment had no obvious effect on the vasoconstrictive reaction to PE and KCl, while its cotreatment obviously mitigated the endothelium-dependent relaxation impairments and the oxidative stress induced by H2O2. The RA cotreatment reversed the downregulation of AMPK and eNOS phosphorylation induced by H2O2 in HAEC cells. The pretreatment with the inhibitors of AMPK (compound C) and eNOS (L-NAME) wiped off RA's beneficial effects. All these results demonstrated that RA attenuated the endothelial dysfunction induced by oxidative stress by activating the AMPK/eNOS pathway.

  9. Rosmarinic Acid Alleviates the Endothelial Dysfunction Induced by Hydrogen Peroxide in Rat Aortic Rings via Activation of AMPK

    Directory of Open Access Journals (Sweden)

    Hui Zhou

    2017-01-01

    Full Text Available Endothelial dysfunction is the key player in the development and progression of vascular events. Oxidative stress is involved in endothelial injury. Rosmarinic acid (RA is a natural polyphenol with antioxidative, antiapoptotic, and anti-inflammatory properties. The present study investigates the protective effect of RA on endothelial dysfunction induced by hydrogen peroxide (H2O2. Compared with endothelium-denuded aortic rings, the endothelium significantly alleviated the decrease of vasoconstrictive reactivity to PE and KCl induced by H2O2. H2O2 pretreatment significantly injured the vasodilative reactivity to ACh in endothelium-intact aortic rings in a concentration-dependent manner. RA individual pretreatment had no obvious effect on the vasoconstrictive reaction to PE and KCl, while its cotreatment obviously mitigated the endothelium-dependent relaxation impairments and the oxidative stress induced by H2O2. The RA cotreatment reversed the downregulation of AMPK and eNOS phosphorylation induced by H2O2 in HAEC cells. The pretreatment with the inhibitors of AMPK (compound C and eNOS (L-NAME wiped off RA’s beneficial effects. All these results demonstrated that RA attenuated the endothelial dysfunction induced by oxidative stress by activating the AMPK/eNOS pathway.

  10. Effect of diesel exhaust particles on renal vascular responses in rats with chronic kidney disease.

    Science.gov (United States)

    Al Suleimani, Y M; Al Mahruqi, A S; Al Za'abi, M; Shalaby, A; Ashique, M; Nemmar, A; Ali, B H

    2017-02-01

    Several recent studies have indicated the possible association between exposure to particulate air pollution and the increased rate of morbidity and mortality in patients with kidney diseases. The link of this observation to vascular damage has not been adequately addressed. Therefore, this study aims to investigate possible vascular damage that might be associated with exposure to diesel exhaust particles (DP) in adenine (AD)-induced chronic kidney disease (CKD) in rats, and the possible ameliorative effect of gum acacia (GA). CKD was induced by feeding AD (0.75%, w/w), and DP (0.5 mg/kg) was instilled intratracheally every second day and GA was given concomitantly in the drinking water at a dose of 15% w/v. All treatments were given concomitantly for 28 days. Changes in renal blood flow (RBF) and systolic and diastolic blood pressure were monitored in these animals after anesthesia, together with several other endpoints. Exposure to DP significantly reduced RBF and this was significantly potentiated in AD-treated rats. Phenylephrine-induced decreases in RBF and increases in systolic and diastolic blood pressure were severely potentiated in rats exposed to DP, and these actions were significantly augmented in AD-treated rats. GA did not significantly affect the vascular impairment induced by AD and DP given together. This study provides experimental evidence that exposure to particulate air pollution can exacerbate the vascular damage seen in patients with CKD. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 541-549, 2017. © 2016 Wiley Periodicals, Inc.

  11. [Effects of vascular peptide bioregulator on cerebral microcirculation of old hypertensive rats].

    Science.gov (United States)

    Sokolova, I B; Sergeev, I V; Ryzhak, G A; Khavinson, V Kh; Kozina, L S

    2017-01-01

    Using a TV device to study brain microcirculation, we found that after a course of vascular peptide bioregulator the density of microvascular network of pia matter of old hypertensive rats (12 months) sensomotor cortex increased about 1,7 times compared to intact old rates SHR. This perfusion in the tissue of the cerebral cortex and the degree of blood oxygen saturation in the microvasculature of this tissue region raised.

  12. Impact of femoral artery puncture using digital subtraction angiography and road mapping on vascular and bleeding complications after transfemoral transcatheter aortic valve implantation.

    Science.gov (United States)

    El-Mawardy, Mohamed; Schwarz, Bettina; Landt, Martin; Sulimov, Dmitriy; Kebernik, Julia; Allali, Abdelhakim; Becker, Bjoern; Toelg, Ralph; Richardt, Gert; Abdel-Wahab, Mohamed

    2017-01-20

    The use of large-diameter sheaths carries the risk of significant vascular and bleeding complications after transfemoral transcatheter aortic valve implantation (TAVI). In this analysis, we sought to assess the impact of a modified femoral artery puncture technique using digital subtraction angiography (DSA) and road mapping during transfemoral TAVI on periprocedural vascular and bleeding events. This is a retrospective analysis of transfemoral TAVI patients included in a prospective institutional database. The modified femoral artery puncture technique using DSA-derived road mapping guidance was introduced in October 2012. Before the introduction of this technique, vascular puncture was acquired based on an integration of angiographic data, the bony iliofemoral landmarks and a radiopaque object. Consecutive patients who underwent TAVI with the road mapping technique (RM group, n=160) were compared with consecutive patients who underwent TAVI without road mapping (control group, n=160) prior to its introduction. A standardised strategy of periprocedural anticoagulation was adopted in both groups as well as the use of a single suture-based closure device. All endpoints were defined according to the VARC-2 criteria for event definition. The mean age in the RM group was 80±7.7 years compared to 81±5.9 years in the control group (p=0.19), and females were equally distributed between both groups (63.1% vs. 58.1%, p=0.36). The baseline logistic EuroSCORE was 20.7±14.4% vs. 24.9±15.2% in the RM and control group, respectively (p=0.01). Notably, sheath size was significantly larger in the RM compared to the control group due to the more frequent use of the 20 Fr sheath (23.8% vs. 1.8%, pstrategy for potentially improving patient outcomes.

  13. Phytoestrogens Enhance the Vascular Actions of the Endocannabinoid Anandamide in Mesenteric Beds of Female Rats

    Directory of Open Access Journals (Sweden)

    Roxana N. Peroni

    2012-01-01

    Full Text Available In rat isolated mesenteric beds that were contracted with NA as an in vitro model of the vascular adrenergic hyperactivity that usually precedes the onset of primary hypertension, the oral administration (3 daily doses of either 10 mg/kg genistein or 20 mg/kg daidzein potentiated the anandamide-induced reduction of contractility to NA in female but not in male rats. Oral treatment with phytoestrogens also restored the vascular effects of anandamide as well as the mesenteric content of calcitonin gene-related peptide (CGRP that were reduced after ovariectomy. The enhancement of anandamide effects caused by phytoestrogens was prevented by the concomitant administration of the estrogen receptor antagonist fulvestrant (2.5 mg/kg, s.c., 3 daily doses. It is concluded that, in the vasculature of female rats, phytoestrogens produced an estrogen-receptor-dependent enhancement of the anandamide-vascular actions that involves the modulation of CGRP levels and appears to be relevant whenever an adrenergic hyperactivity occurs.

  14. O-GlcNAc modification of NFκB p65 inhibits TNF-α-induced inflammatory mediator expression in rat aortic smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Dongqi Xing

    Full Text Available BACKGROUND: We have shown that glucosamine (GlcN or O-(2-acetamido-2-deoxy-D-glucopyranosylideneamino-N-phenylcarbamate (PUGNAc treatment augments O-linked-N-acetylglucosamine (O-GlcNAc protein modification and attenuates inflammatory mediator expression, leukocyte infiltration and neointima formation in balloon injured rat carotid arteries and have identified the arterial smooth muscle cell (SMC as the target cell in the injury response. NFκB signaling has been shown to mediate the expression of inflammatory genes and neointima formation in injured arteries. Phosphorylation of the p65 subunit of NFκB is required for the transcriptional activation of NFκB. This study tested the hypothesis that GlcN or PUGNAc treatment protects vascular SMCs against tumor necrosis factor (TNF-α induced inflammatory stress by enhancing O-GlcNAcylation and inhibiting TNF-α induced phosphorylation of NFκB p65, thus inhibiting NFκB signaling. METHODOLOGY/PRINCIPAL FINDINGS: Quiescent rat aortic SMCs were pretreated with GlcN (5 mM, PUGNAc (10(-4 M or vehicle and then stimulated with TNF-α (10 ng/ml. Both treatments inhibited TNF-α-induced expression of chemokines [cytokine-induced neutrophil chemoattractant (CINC-2β and monocyte chemotactic protein (MCP-1] and adhesion molecules [vascular cell adhesion molecule (VCAM-1 and P-Selectin]. Both treatments inhibited TNF-α induced NFκB p65 activation and promoter activity, increased NFκB p65 O-GlcNAcylation and inhibited NFκB p65 phosphorylation at Serine 536, thus promoting IκBα binding to NFκB p65. CONCLUSIONS: There is a reciprocal relationship between O-GlcNAcylation and phosphorylation of NFκB p65, such that increased NFκB p65 O-GlcNAc modification inhibits TNF-α-Induced expression of inflammatory mediators through inhibition of NFκB p65 signaling. These findings provide a mechanistic basis for our previous observations that GlcN and PUGNAc treatments inhibit inflammation and remodeling induced by

  15. Persistent fifth arch anomalies - broadening the spectrum to include a variation of double aortic arch vascular ring

    Energy Technology Data Exchange (ETDEWEB)

    Newman, Beverley; Chan, Frandics [Stanford Children' s Hospital and Stanford University, Department of Radiology, Stanford, CA (United States); Hanneman, Kate [University of Toronto, Department of Medical Imaging, Toronto, ON (Canada)

    2016-12-15

    Fifth arch anomalies are rare and complex and frequently misdiagnosed or mistaken for other entities. We report a double arch vascular ring that is thought to consist of right fourth arch and left fifth arch components, a previously undescribed persistent fifth arch variant. The currently recognized spectrum and classification of fifth arch vascular anomalies are expanded along with illustrative images to justify the proposed changes. Reviewing and expanding the classification of fifth arch anomalies to include a double arch ring variant will promote recognition, correct diagnosis and appropriate management of these anomalies. (orig.)

  16. Chronic hypoxia increases fetoplacental vascular resistance and vasoconstrictor reactivity in the rat.

    Science.gov (United States)

    Jakoubek, Vít; Bíbová, Jana; Herget, Jan; Hampl, Václav

    2008-04-01

    An increase in fetoplacental vascular resistance caused by hypoxia is considered one of the key factors of placental hypoperfusion and fetal undernutrition leading to intrauterine growth restriction (IUGR), one of the serious problems in current neonatology. However, although acute hypoxia has been shown to cause fetoplacental vasoconstriction, the effects of more sustained hypoxic exposure are unknown. This study was designed to test the hypothesis that chronic hypoxia elicits elevations in fetoplacental resistance, that this effect is not completely reversible by acute reoxygenation, and that it is accompanied by increased acute vasoconstrictor reactivity of the fetoplacental vasculature. We measured fetoplacental vascular resistance as well as acute vasoconstrictor reactivity in isolated perfused placentae from rats exposed to hypoxia (10% O(2)) during the last week of a 3-wk pregnancy. We found that chronic hypoxia shifted the relationship between perfusion pressure and flow rate toward higher pressure values (by approximately 20%). This increased vascular resistance was refractory to a high dose of sodium nitroprusside, implying the involvement of other factors than increased vascular tone. Chronic hypoxia also increased vasoconstrictor responses to angiotensin II (by approximately 75%) and to acute hypoxic challenges (by >150%). We conclude that chronic prenatal hypoxia causes a sustained elevation of fetoplacental vascular resistance and vasoconstrictor reactivity that are likely to produce placental hypoperfusion and fetal undernutrition in vivo.

  17. Responses of the isolated aortic rings of rats to some vasoactive ...

    African Journals Online (AJOL)

    Similar experiments were conducted after incubation of the aortic rings with 2׳, 5׳ dideoxy adenosine (DDA), methylene blue (MB) and L-N nitroarginine (L- NNA) in the three different channels and thereafter relaxed these with forskolin (FSK) and SNP. The results showed that acetylcholine and sodium nitroprusside caused ...

  18. [Effect of paeonol on LPS-induced rat vascular endothelial cell adhesion reaction].

    Science.gov (United States)

    Chen, Jun-Jun; Dai, Min; Chen, Peng

    2013-03-01

    To observe the effect of Paeonol (Pae) on lipopolysaccharide (LPS) induced rat mononuclear cells (MCs) adhesion to vascular endothelial cells (VECs) and provide basis foundation for inflammatary mechanisms of Pae against atherosclerosis. Rat vascular endothelial cells were isolated with tissue predigested adherent method. LPS was used as stimulator to induce VEC injury. Serum containing Pae obtained from healthy rats which were given Pae in intragastric. RP-HPLC method was used for detecting the concentration of Pae in serum. MTT assay was used to determine the protective effect of Pae on injured VECs. Rose Bengal Staining was used to detect the effect of Pae on LPS-induced MCs adhesion to VECs. LPS induced rat MCs adhesion to VECs. The effect was the strongest when the concentration was 10 ng/mL and incubated with VECs for 5 h. Pae in concentration of 2. 5,5 and 10 microg/mL and incubated for 24 h could effectively inhibit the adhesion and improve the survival rate of LPS injured VECs significantly. LPS can damage VECs. Pae could protect VECs from LPS injury via inhibiting MCs adhesion to VECs and improving the VEC survival rate.

  19. Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Tharciano Luiz Teixeira Braga da; Mota, Marcelo Mendonça; Fontes, Milene Tavares; Araújo, João Eliakim dos Santos; Carvalho, Vitor Oliveira; Bonjardim, Leonardo Rigoldi; Santos, Márcio Roberto Viana, E-mail: marciorvsantos@bol.com.br [Universidade Federal de Sergipe, Universidade de São Paulo (Brazil)

    2015-08-15

    Hypertension is a public health problem and increases the incidence of cardiovascular diseases. To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of N{sup G}-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats. Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP). Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H. One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

  20. Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI.

    Directory of Open Access Journals (Sweden)

    Guangliang Ding

    Full Text Available Treatment of stroke with bone marrow stromal cells (BMSC significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM. T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo. T2DM rats received BMSC (5x106, n = 8 or an equal volume of phosphate-buffered saline (PBS (n = 8 via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in T2DM rats significantly (p<0.05 decreased blood-brain barrier disruption starting at 1 week post stroke measured using contrast enhanced T1-weighted imaging with gadopentetate, and reduced cerebral hemorrhagic spots starting at 3 weeks post stroke measured using susceptibility weighted imaging, although BMSC treatment did not reduce the ischemic lesion volumes as demarcated by T2 maps. These MRI measurements were consistent with histological data. Thus, BMSC treatment of stroke in T2DM rats initiated at 3 days after stroke significantly reduced ischemic vascular damage, although BMSC treatment did not change infarction volume in T2DM rats, measured by MRI.

  1. Vascular calcification abrogates the nicorandil mediated cardio-protection in ischemia reperfusion injury of rat heart.

    Science.gov (United States)

    Ravindran, Sriram; Murali, Jeyashri; Amirthalingam, Sunil Kumar; Gopalakrishnan, Senthilkumar; Kurian, Gino A

    2017-02-01

    The present study was aimed to determine the efficacy of nicorandil in treating cardiac reperfusion injury with an underlying co-morbidity of vascular calcification (VC). Adenine diet was used to induce VC in Wistar rat and the heart was isolated to induce global ischemia reperfusion (IR) by Langendorff method, with and without the nicorandil (7.5mg/kg) pre-treatment and compared with those fed on normal diet. The adenine-treated rats displayed abnormal ECG changes and altered mitochondrial integrity compared to a normal rat heart. These hearts, when subjected to IR increased the infarct size, cardiac injury (measured by lactate dehydrogenase and creatine kinase activity in the coronary perfusate) and significantly altered the hemodynamics compared to the normal perfused heart. Nicorandil pretreatment in rat fed on normal diet enhanced the hemodynamics significantly (Pcardio-protective effect of nicorandil was absent in rat heart with underlying calcification. Our results suggest that, the protective effect of nicorandil, a known mitochondrial ATP linked K + channel opener, against myocardial reperfusion injury was confined to normal rat heart. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Chronic skeletal unloading of the rat femur: mechanisms and functional consequences of vascular remodeling.

    Science.gov (United States)

    Stabley, John N; Prisby, Rhonda D; Behnke, Bradley J; Delp, Michael D

    2013-12-01

    Chronic skeletal unloading diminishes hindlimb bone blood flow. The purpose of the present investigation was to determine 1) whether 7 and 14days of skeletal unloading alter femoral bone and marrow blood flow and vascular resistance during reloading, and 2) whether putative changes in bone perfusion are associated with a gross structural remodeling of the principal nutrient artery (PNA) of the femur. Six-month old male Sprague-Dawley rats were assigned to 7-d or 14-d hindlimb unloading (HU) or weight-bearing control groups. Bone perfusion was measured following 10min of standing (reloading) following the unloading treatment. Histomorphometry was used to determine PNA media wall thickness and maximal diameter. Bone blood flow, arterial pressure and PNA structural characteristics were used to calculate arterial shear stress and circumferential wall stress. During reloading, femoral perfusion was lower in the distal metaphyseal region of 7-d HU rats, and in the proximal and distal metaphyses, diaphysis and diaphyseal marrow of 14-d HU animals relative to that in control rats. Vascular resistance was also higher in all regions of the femur in 14-d HU rats during reloading relative to control animals. Intraluminal diameter of PNAs from 14-d HU rats (138±5μm) was smaller than that of control PNAs (162±6μm), and medial wall thickness was thinner in PNAs from 14-d HU (14.3±0.6μm) versus that of control (18.0±0.8μm) rats. Decreases in both shear stress and circumferential stress occurred in the PNA with HU that later returned to control levels with the reductions in PNA maximal diameter and wall thickness, respectively. The results demonstrate that chronic skeletal unloading attenuates the ability to increase blood flow and nutrient delivery to bone and marrow with immediate acute reloading due, in part, to a remodeling of the bone resistance vasculature. © 2013.

  3. Editor's Highlight: Pulmonary Vascular Thrombosis in Rats Exposed to Inhaled Sulfur Mustard.

    Science.gov (United States)

    McGraw, Matthew D; Osborne, Christopher M; Mastej, Emily J; Di Paola, Jorge A; Anderson, Dana R; Holmes, Wesley W; Paradiso, Danielle C; Garlick, Rhonda B; Hendry-Hofer, Tara B; Rancourt, Raymond C; Smith, Russell W; Burns, Carol; Roe, Gates B; Rioux, Jacqueline S; White, Carl W; Veress, Livia A

    2017-10-01

    Sulfur mustard (SM) is a chemical warfare agent. When inhaled, SM causes significant injury to the respiratory tract. Although the mechanism involved in acute airway injury after SM inhalation has been well described previously, the mechanism of SM's contribution to distal lung vascular injury is not well understood. We hypothesized that acute inhalation of vaporized SM causes activated systemic coagulation with subsequent pulmonary vascular thrombi formation after SM inhalation exposure. Sprague Dawley rats inhaled SM ethanolic vapor (3.8 mg/kg). Barium/gelatin CT pulmonary angiograms were performed to assess for pulmonary vascular thrombi burden. Lung immunohistochemistry was performed for common procoagulant markers including fibrin(ogen), von Willebrand factor, and CD42d in control and SM-exposed lungs. Additionally, systemic levels of d-dimer and platelet aggregometry after adenosine diphosphate- and thrombin-stimulation were measured in plasma after SM exposure. In SM-exposed lungs, chest CT angiography demonstrated a significant decrease in the distal pulmonary vessel density assessed at 6 h postexposure. Immunohistochemistry also demonstrated increased intravascular fibrin(ogen), vascular von Willebrand factor, and platelet CD42d in the distal pulmonary vessels (<200 µm diameter). Circulating d-dimer levels were significantly increased (p < .001) at 6, 9, and 12 h after SM inhalation versus controls. Platelet aggregation was also increased in both adenosine diphosphate - (p < .01) and thrombin- (p < .001) stimulated platelet-rich plasma after SM inhalation. Significant pulmonary vascular thrombi formation was evident in distal pulmonary arterioles following SM inhalation in rats assessed by CT angiography and immunohistochemistry. Enhanced systemic platelet aggregation and activated systemic coagulation with subsequent thrombi formation likely contributed to pulmonary vessel occlusion. © The Author 2017. Published by Oxford University Press on

  4. The effects of epinine on arterial blood pressure and regional vascular resistances in anesthetized rats.

    Science.gov (United States)

    Martínez-Mir, I; Palop, V; Morales-Olivas, F J; Estañ, L; Rubio, E

    1998-07-01

    1. We carried out experiments in anesthetized rats to study the hemodynamic effects of intravenous injections of epinine. 2. Epinine (1-320 micrograms/kg) produced a biphasic effect on mean arterial blood pressure (n = 30). At doses lower than 40 micrograms/kg, arterial blood pressure decreased (by as much as 21.5 +/- 3.4%), though at higher doses it increased dose dependently (by as much as 73.2 +/- 14.5%). Epinine also produced bradicardia in a dose-dependent manner (by as much as 26.4 +/- 4.9%). Sulpiride (100 micrograms/kg) suppressed the hypotensive effect of epinine but did not change the hypertensive effect. In the presence of prazosin (1,000 micrograms/kg), arterial blood pressure remained significantly decreased at all doses of epinine. Neither sulpiride nor prazosin changed the bradycardic effect of epinine. 3. Prazosin produced a significant decrease in renal vascular resistance. Epinine (5 micrograms/kg) after prazosin reverted the effects of prazosin in renal vascular resistance, without any significant modification in the renal blood flows. However, 20 micrograms/kg epinine increased the renal vascular resistances and, moreover, produced a significant decrease in the blood flows of both kidneys. Neither prazosin nor epinine produced modifications in the intestinal vascular bed. 4. Although epinine possesses significant dopamine and alpha-adrenergic activities that are involved in the biphasic effect of the agent on mean arterial blood pressure in anesthetized rats, in the presence of prazosin, it is not possible to manifest dopaminergic activity involved in the increase in renal or mesenteric blood flow; this may be due to the low tone of the vascular wall induced by the alpha-adrenergic antagonist, though an alpha 2-activity cannot be discarded.

  5. The calcimimetic AMG 641 abrogates parathyroid hyperplasia, bone and vascular calcification abnormalities in uremic rats.

    Science.gov (United States)

    Henley, Charles; Davis, James; Miller, Gerald; Shatzen, Edward; Cattley, Russ; Li, Xiaodong; Martin, David; Yao, Wei; Lane, Nancy; Shalhoub, Victoria

    2009-08-15

    Calcimimetics and vitamin D sterols reduce serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism receiving dialysis, a disease state associated with parathyroid hyperplasia, vascular calcification, bone disease, and increased mortality. The aim of this study was to determine the effects of the research calcimimetic AMG 641 (Amgen, Inc., Thousand Oaks, CA) or calcitriol (Sigma Aldrich Corporation, St. Louis, MO) on vascular calcification in a rodent model of progressive uremia with accompanying secondary hyperparathyroidism induced by dietary adenine. Treatment effects on parathyroid gland hyperplasia and bone loss were also investigated. Rats were treated daily with vehicle, calcitriol (10 ng), AMG 641 (3 mg/kg), or no treatment during the 4 week period the animals were fed adenine. The uremia-induced increases in serum PTH levels were significantly attenuated by both AMG 641 (>90%) and calcitriol (approximately 50%). AMG 641 significantly reduced calcium-phosphorus product (CaxP) and significantly attenuated the development of both parathyroid hyperplasia and vascular calcification. In addition, AMG 641 prevented the defects in trabecular bone volume, trabecular number, and bone mineralization, as well as increases in trabecular spacing in this rodent model of secondary hyperparathyroidism. Calcitriol (10 ng/rat) decreased osteoid surface/bone surface, but had no effects on other bone parameters, or parathyroid hyperplasia (likely due to the lower PTH suppressive effect of calcitriol at the dose used in this study). However, this dose of calcitriol significantly exacerbated vascular calcification. These results suggest that calcimimetics can reduce the development of vascular calcification, parathyroid hyperplasia and bone abnormalities associated with secondary hyperparathyroidism.

  6. The effects of angiotensin II receptor antagonist (candesartan on rat renal vascular resistance

    Directory of Open Access Journals (Sweden)

    Supatraviwat, J

    2004-05-01

    Full Text Available The present study aimed to investigate the action of angiotensin II (AII on renal perfusion pressure and renal vascular resistance using noncompetitive AT1-receptor antagonist (candesartan or CV 11974. Experiments were performed in isolated kidney of adult male Wistar rats. Kreb's Henseleit solution was perfused into the renal artery at the rate of 3.5 ml/min. This flow rate was designed in order to maintain renal perfusion pressure between 80-120 mm Hg. Dose-response relationship between perfusion flow rate and AII concentration were studied. Renal perfusion pressure in response to 1, 10 and 100 nM AII were increased from basal perfusion pressure of 94±8 mm Hg to 127±6, 157±12 and 190±16 mm Hg, respectively. Administration of perfusate containing 11.4 μM candesartan for 30 min had no effect on the basal perfusion pressure. However, this significantly reduced renal perfusion pressure in the presence of AII (1, 10 and 100 nM by 39%, 47% and 61%, (n=7, P<0.05 respectively. At the basal perfusion pressure, calculated renal vascular resistance was 27±2 mm Hg · min · ml-1. However, the vascular resistance were found to be 41±1, 45±2 and 47±2 mm Hg · min · ml-1 when 1, 10 and 100 nM AII were added. Moreover, this dose of candesartan also showed a significant decrease in renal vascular resistance at the corresponding doses of AII by 38%, 48% and 43%, (n=7, P<0.05 respectively. The higher dose of candesartan (22.7 μM completely inhibited the action of 1, 10 and 100 nM AII on renal vasoconstriction. These results may indicate that the action of AII on renal vascular resistance is via AT1-receptor, at least in rat isolated perfusion kidney.

  7. Effects of unfractionated heparin on renal osteodystrophy and vascular calcification in chronic kidney disease rats.

    Science.gov (United States)

    Meng, Yan; Zhang, Hao; Li, Yingbin; Li, Qingnan; Zuo, Li

    2014-01-01

    Unfractionated heparin (UFH) is the most widely used anticoagulant in hemodialysis for chronic kidney disease (CKD) patients. Many studies have verified that UFH can induce bone loss in subjects with normal bone, but few have focused on its effect on renal osteodystrophy. We therefore investigated this issue in adenine-induced CKD rats. As CKD also impairs mineral metabolism systemically, we also studied the impacts of UFH on serum markers of CKD-mineral and bone disorder (CKD-MBD) and vascular calcification. We administered low and high doses of UFH (1U/g and 2U/g body weight, respectively) to CKD rats and compared them with CKD controls. At sacrifice, the serum markers of CKD-MBD did not significantly differ among the two UFH CKD groups and the CKD control group. The mean bone mineral densities (BMDs) of the total femur and a region of interest (ROI) constituted of trabecular and cortical bone were lower in the high-dose UFH (H-UFH) CKD group than in the CKD control group (Prats indicated secondary hyperparathyroidism, and the femoral trabecular bone volume, but not cortical bone volume, significantly decreased with increasing UFH dose. The same decreasing trend was found in osteoblast parameters, and an increasing trend was found in osteoclast parameters; however, most differences were not significant. Moreover, no distinct statistical differences were found in the comparison of vascular calcium or phosphorus content among the CKD control group and the two UFH CKD groups. Therefore, we concluded that UFH could induce bone loss in CKD rats with secondary hyperparathyroidism, mainly by reducing the trabecular volume and had little effect on cortical bone volume. The underlying mechanism might involve inhibition of osteoblast activity and promotion of osteoclast activity by UFH. We did not find any effect of UFH on vascular calcification in CKD rats with secondary hyperparathyroidism. © 2013.

  8. Tryptophan hydroxylase 1 Inhibition Impacts Pulmonary Vascular Remodeling in Two Rat Models of Pulmonary Hypertension.

    Science.gov (United States)

    Aiello, Robert J; Bourassa, Patricia-Ann; Zhang, Qing; Dubins, Jeffrey; Goldberg, Daniel R; De Lombaert, Stéphane; Humbert, Marc; Guignabert, Christophe; Cavasin, Maria A; McKinsey, Timothy A; Paralkar, Vishwas

    2017-02-01

    Pulmonary arterial hypertension (PAH) is a progressive disease defined by a chronic elevation in pulmonary arterial pressure with extensive pulmonary vascular remodeling and perivascular inflammation characterized by an accumulation of macrophages, lymphocytes, dendritic cells, and mast cells. Although the exact etiology of the disease is unknown, clinical as well as preclinical data strongly implicate a role for serotonin (5-HT) in the process. Here, we investigated the chronic effects of pharmacological inhibition of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in peripheral 5-HT biosynthesis, in two preclinical models of pulmonary hypertension (PH), the monocrotaline (MCT) rat and the semaxanib (SUGEN, Medinoah, Suzhou, China)-hypoxia rat. In both PH models, ethyl (S)-8-(2-amino-6-((R)-1-(5-chloro-[1,1'-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate and ethyl (S)-8-(2-amino-6-((R)-1-(3',4'-dimethyl-3-(3-methyl-1 H-pyrazol-1-yl)-[1,1'-biphenyl]-4-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate, novel orally active TPH1 inhibitors with nanomolar in vitro potency, decreased serum, gut, and lung 5-HT levels in a dose-dependent manner and significantly reduced pulmonary arterial pressure, and pulmonary vessel wall thickness and occlusion in male rats. In the MCT rat model, decreases in lung 5-HT significantly correlated with reductions in histamine levels and mast cell number (P pulmonary vascular remodeling and pressures. These data demonstrate that in addition to reducing vascular remodeling, TPH1 inhibition has the added benefit of reducing the perivascular mast cell accumulation associated with PH. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  9. Effects of Crocetin Esters and Crocetin from Crocus sativus L. on Aortic Contractility in Rat Genetic Hypertension

    Directory of Open Access Journals (Sweden)

    Silvia Llorens

    2015-09-01

    Full Text Available Background: Endothelial dysfunction, characterized by an enhancement in vasoconstriction, is clearly associated with hypertension. Saffron (Crocus sativus L. bioactive compounds have been recognized to have hypotensive properties. Recently, we have reported that crocetin exhibits potent vasodilator effects on isolated aortic rings from hypertensive rats. In this work, we have aimed to analyze the anticontractile ability of crocetin or crocetin esters pool (crocins isolated from saffron. Thus, we have studied the effects of saffron carotenoids on endothelium-dependent and -independent regulation of smooth muscle contractility in genetic hypertension. Methods: We have measured the isometric responses of aortic segments with or without endothelium obtained from spontaneously hypertensive rats. The effects of carotenoids were studied by assessing the endothelial modulation of phenylephrine-induced contractions (10−9–10−5 M in the presence or absence of crocetin or crocins. The role of nitric oxide and prostanoids was analyzed by performing the experiments with L-NAME (NG-nitro-l-arginine methyl ester or indomethacin (both 10−5 M, respectively. Results: Crocetin, and to a minor extent crocins, diminished the maximum contractility of phenylephrine in intact rings, while crocins, but not crocetin, increased this contractility in de-endothelizated vessels. In the intact vessels, the effect of crocetin on contractility was unaffected by indomethacin but was abolished by L-NAME. However, crocetin but not crocins, lowered the already increased contractility caused by L-NAME. Conclusions: Saffron compounds, but especially crocetin have endothelium-dependent prorelaxing actions. Crocins have procontractile actions that take place via smooth muscle cell mechanisms. These results suggest that crocetin and crocins activate different mechanisms involved in the vasoconstriction pathway in hypertension.

  10. Calcium dobesilate attenuates vascular injury and the progression of diabetic retinopathy in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Padilla, Eugenia; Ganado, Patricia; Sanz, Mercedes; Zeini, Miriam; Ruiz, Emilio; Triviño, Alberto; Ramírez, Ana I; Salazar, Juan J; Ramírez, Jose M; Rojas, Blanca; Hoz, Rosa de; Tejerina, Teresa

    2005-01-01

    Diabetic retinopathy (DR) is a highly specific vascular complication of type 1 and type 2 diabetes mellitus. Calcium dobesilate (DOBE) has been tested in the treatment of diabetic retinopathy showing a slowdown of the progression of the disease after long-term oral treatment. The aim of this study was to determine the effects of DOBE on vascular and diabetic retinopathy in streptozotocin (STZ) diabetic rats. Diabetes was induced in wistar rats by the administration of STZ (60 mg/kg, i.p.). Rats were divided into three groups (n = 30). Group 0 (GO): nondiabetic rats. Group 1 (G1): 14 months of insulin treatment after diabetes development. Group 2 (G2): 14 months of insulin treatment after diabetes development plus DOBE (500 mg/kg/day). At the end of the treatment, vascular reactivity was tested. The study of the vascularization of the retina was performed on wholemounts of trypsin retinal digest preparations and retinal sections. Relaxation induced by acetylcholine decreased in the aorta arteries from diabetic rats but it was restored to control values in the DOBE-treated group (71.8 +/- 4.5%, 53.3 +/- 0.5%, 67.4 +/- 4.6% in group 0, 1 and 2 respectively). DOBE treatment also restored noradrenaline (1.08 +/- 0.05 g, 1.70 +/- 0.08 g, 1.13 +/- 0.05 g in group 0, 1 and 2 respectively) and caffeine-induced contractions. Diabetic state did not cause any alteration in mesenteric arteries. The analysis of the retinal digests showed vascular tortuosity, acellular capillaries, focal accumulations of capillaries and reduction of the number of pericytes in G1. The vascular changes observed in G2 seem to be intermediate between the control and the diabetic rats. We showed that long-term treatment with DOBE attenuated the progression of diabetic retinopathy and the alterations in vascular reactivity in streptozotocin-induced diabetic rats. Copyright 2004 John Wiley & Sons, Ltd.

  11. Candesartan and amlodipine combination therapy provides powerful vascular protection in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Takai, Shinji; Jin, Denan; Shimosato, Takashi; Sakonjo, Hiroshi; Miyazaki, Mizuo

    2011-02-01

    The vascular protective effects of placebo, candesartan (1 mg kg(-1) per day) monotherapy, candesartan (1 mg kg(-1) per day) and amlodipine (1 mg kg(-1) per day) combination therapy, and candesartan (1 mg kg(-1) per day) and hydrochlorothiazide (HCTZ) (10 mg kg(-1) per day) combination therapy for 2 weeks were compared in stroke-prone, spontaneously hypertensive rats. Candesartan monotherapy significantly reduced blood pressure, and both combination therapies were equally and significantly lower than the monotherapy. Acetylcholine-induced vascular relaxation was significantly stronger in all therapeutic groups than in the placebo-treated group. Furthermore, the relaxation was significantly stronger in the candesartan plus amlodipine-treated group than in the candesartan-treated group; however, there was no significant difference between the candesartan- and candesartan plus HCTZ-treated groups. Vascular gene expressions of the NADPH oxidase subunits p22(phox), gp91(phox), NOX1 and NOX4 were significantly attenuated in all therapeutic groups compared with the placebo-treated group, and there were no significant differences among those groups. However, a significant augmentation of vascular superoxide dismutase activity was observed in the candesartan plus amlodipine-treated group, but not in other groups. Malondialdehyde levels in the vascular tissues were significantly attenuated in all therapeutic groups. Compared with the candesartan-treated group, significant attenuation was observed in the candesartan plus amlodipine-treated group, but not in the candesartan plus HCTZ-treated group. Immunohistological analysis showed that areas positive for 4-hydroxy-2-nonenal were significantly reduced in all therapeutic groups, but this reduction was significantly greater for the candesartan plus amlodipine-treated group than for the candesartan-treated group. Thus, candesartan and amlodipine combination therapy could have a powerful protective effect in vascular tissues via

  12. Vasodilator and vasoconstriction inhibitor effect of Olea europaea (olive) leaf hydroalcoholic extract on rat aortic rings

    OpenAIRE

    Nexar-QH, Job; Estudiante de medicina, Universidad Nacional de San Agustín, Arequipa, Perú. Centro de Investigación y Desarrollo Científico, Facultad de Medicina, Universidad Nacional de San Agustín, Arequipa, Perú. Sociedad Científica de Estudiantes de Medicina Agustinos, Arequipa, Perú.; Sillo-Surco, Jhon; Estudiante de medicina, Universidad Nacional de San Agustín, Arequipa, Perú. Centro de Investigación y Desarrollo Científico, Facultad de Medicina, Universidad Nacional de San Agustín, Arequipa, Perú. Sociedad Científica de Estudiantes de Medicina Agustinos, Arequipa, Perú.

    2014-01-01

    Objectives: To determine the vasodilator and anti-vasoconstrictor effect of Olea europaea (olive) leaf hydroalcoholic extract on rataortic rings and the mechanism involved. Design: Experimental. Location: Research and Scientific Development Center, Faculty ofMedicine, Universidad Nacional de San Agustin, Arequipa, Peru. Biological material: Leaves of Olea europaea and aortic rings ofRattus norvegicus, swiss albina variety. Interventions: Hydroalcoholic extract was obtained from Olea europaea ...

  13. Imatinib inhibits vascular smooth muscle proteoglycan synthesis and reduces LDL binding in vitro and aortic lipid deposition in vivo

    Science.gov (United States)

    Ballinger, Mandy L; Osman, Narin; Hashimura, Kazuhiko; de Haan, Judy B; Jandeleit-Dahm, Karin; Allen, Terri; Tannock, Lisa R; Rutledge, John C; Little, Peter J

    2010-01-01

    Abstract The ‘response to retention’ hypothesis of atherogenesis proposes that proteoglycans bind and retain low-density lipoproteins (LDL) in the vessel wall. Platelet-derived growth factor (PDGF) is strongly implicated in atherosclerosis and stimulates proteoglycan synthesis. Here we investigated the action of the PDGF receptor inhibitor imatinib on PDGF-mediated proteoglycan biosynthesis in vitro, lipid deposition in the aortic wall in vivo and the carotid artery ex vivo. In human vSMCs, imatinib inhibited PDGF mediated 35S-SO4 incorporation into proteoglycans by 31% (P proteoglycans from PDGF stimulated cells in the presence of imatinib was approximately 2.5-fold higher than for PDGF treatment alone. In high fat fed ApoE−/– mice, imatinib reduced total lipid staining area by ∼31% (P proteoglycans and reduces LDL binding in vitro and in vivo and this effect is mediated via the PDGF receptor. These findings validate a novel mechanism to prevent cardiac disease. PMID:19754668

  14. Evaluation with Doppler vascular ultrasound in postoperative endovascular treatment of abdominal aortic aneurysm: a prospective comparative study with angiotomography

    Directory of Open Access Journals (Sweden)

    Graciliano Jose Franca

    2013-06-01

    Full Text Available BACKGROUND: Diagnosis of abdominal aortic aneurysm (AAA is usually incidental, and surgical treatment, when indicated, may be open or endovascular. The drawbacks of computed angiotomography (CTA and the advantages of Doppler ultrasonography have led to the development of alternative follow-up protocols, comparing the two methods. OBJECTIVE: To determine validity indices for Doppler ultrasonography and to correlate them with CTA results in a group of patients who had undergone elective endovascular treatment of AAAs. MATERIAL AND METHODS: Thirty-three patients were selected. The following three items were evaluated: 1 presence or absence of endoleak; 2 presence of blood flow in the aortoiliac segment; and 3 maximum AAA diameter. RESULTS: For the detection of endoleak, Doppler ultrasonography showed a sensitivity of 54.5%, a specificity of 92.8%, a positive predictive value of 85.7%, a negative predictive value of 92.8%, and an overall accuracy of 76%. For the evaluation of blood flow in the aortoiliac segment, values were 100, 97.8, 80, 97.8, and 98%, respectively. Maximum AAA diameter was similarly measured by both methods, with statistically significant differences (mean difference: 1.98 mm. Pearson's correlation coefficient was 0.97, showing that Doppler ultrasonography and CTA yielded similar results. CONCLUSION: Doppler ultrasonography showed good validity indices and a moderate correlation with CTA in the postoperative evaluation of patients undergoing endovascular treatment of AAAs.

  15. CIDEC Gene Silencing Alleviates Pulmonary Vascular Remodeling in a Type 2 Diabetic Rat Model.

    Science.gov (United States)

    Sui, Dong-Xin; Zhou, Hui-Min; Wang, Feng; Zhong, Ming; Zhang, Wei; Ti, Yun

    2017-10-27

    CIDEC was proven to be closely associated with the development of insulin resistance and metabolic syndrome. We aimed to investigate whether the CIDEC gene silencing could alleviate pulmonary vascular remodeling in a type 2 diabetic rat model. We built a type 2 diabetic rat model. An adenovirus harboring CIDEC small interfering RNA (siRNA) was then injected via the jugular vein to silence the CIDEC gene. After HE and Sirius red staining, we detected indexes of the pulmonary arterioles remodeling. Immunohistochemical staining of PCNA was used to evaluate the pulmonary arterial smooth muscle cell proliferation. Apoptosis was evaluated by TUNEL reaction and Western-blotting. The levels of signaling pathway proteins expression were measured by Western-blotting analyses. Histological analysis of pulmonary artery showed that the thickness of the adventitia and medial layer increased notably in type 2 diabetic rats. Immunohistochemistry showed that more PCNA positive pulmonary arterial smooth muscle cells could be seen in type 2 diabetic rats, and after CIDEC gene silencing PCNA positive cells decreased accordingly. Cleaved caspase-3 and Cleaved PARP measured by Western-blotting indicated increased apoptosis with overexpressed CIDEC in diabetes. TUNEL reaction showed that the apoptosis mainly occurred in endothelial cells. Western-blotting analysis demonstrated CIDEC overexpression in rats with diabetes, and phosphorylated AMPKα expression was significantly decreased. After CIDEC gene silencing, the expression of phosphorylated AMPKα was up-regulated. CIDEC/AMPK signaling pathway could be a potential therapeutic candidate against pulmonary vascular diseases in type 2 diabetes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. [Effect of sesamin on pulmonary vascular remodeling in rats with monocrotaline-induced pulmonary hypertension].

    Science.gov (United States)

    Li, Xian-wei; Gao, Yun-xing; Li, Shu; Yang, Jie-ren

    2015-04-01

    To observe the effect of sesamin (Ses) on pulmonary vascular remodeling in rats with monocrotaline ( MCT)-induced pulmonary hypertension (PH). Totally 48 male Sprague-Dawley (SD) rats were fed adaptively for one week and then divided into the normal control group, the MCT group, the MCT +Ses (50 mg x kg(-1)) group and the MCT + Ses (100 mg x kg(-1)) group, with 12 rats in each group. The PH rat model was induced through the subcutaneous injection with MCT(60 mg x kg(-1)). After the administration for four weeks, efforts were made to measure the right ventricular systolic pressure( RVSP) and mean pulmonary artery pressure (mPAP) through right jugular vein catheterization, and isolate right ventricle( RV) and left ventricle( LV) +septum (S) and measure their length to calculate RV/ ( LV + S) and ratio of RV to tibial length. Pathologic changes in arterioles were observed by HE staining. Masson's trichrome stain was used to demonstrate changes in collagen deposition of arterioles. The alpha-smooth muscle actin (alpha-SMA) expression in pulmonary arteries was measured by immunohistochemisty. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) content in pulmonary arteries were determined by the colorimetric method. The protein expressions of collagen I, NOX2 and NOX4 were analyzed by Real-time PCR and Western blot. After the administration for 4 weeks, Ses could attenuate RVSP and mPAP induced by MCT, RV/ (LV + S) and ratio of RV to Tibial length, alpha-SMA and collagen I expressions and remodeling of pulmonary vessels and right ventricle. Meanwhile, Ses could obviously inhibit the expressions of NOX2, NOX4 and MDA content and increase T-AOC. Sesamin could ameliorate pulmonary vascular remodeling induced by monocrotaline in PH rats. Its mechanism may be related to expressions of NOX2 and NOX4 expression and reduction in oxidative stress injury.

  17. Echocardiographic integrated backscatter for assessing reduction of aortic valve calcifications by R-568 in a rat model of chronic kidney disease.

    Science.gov (United States)

    Roosens, Bram; Bala, Gezim; Droogmans, Steven; Hostens, Jeroen; Somja, Joan; Delvenne, Eléonore; Schiettecatte, Johan; Delvenne, Philippe; Caveliers, Vicky; Lahoutte, Tony; Van Camp, Guy; Cosyns, Bernard

    2013-11-01

    Chronic kidney disease (CKD) and secondary hyper-parathyroidism are associated with calcific aortic valve disease (CAVD). Innovative modalities for imaging CAVD are warranted. Our aim was to use echocardiographic calibrated integrated backscatter (cIB) to quantitatively determine the preventive effect of the calcimimetic R-568 on CAVD in a CKD rat model, and to compare the results with those of micro-computed tomography and histology. Thirty-six male Wistar rats were followed for 7 wk. Rats were divided into four groups with respect to treatment: (1) adenine 0.5% to induce CKD + vehicle; (2) adenine + R-568 (30 mg/kg/d); (3) control, normal diet + vehicle; (4) controls, normal diet + R-568. At week 7, cIB values of the aortic valve were significantly lower in R-568-treated group 2 than in vehicle-treated group 1. This was confirmed by the significantly lower calcified volume observed on micro-computed tomography and the calcified area observed on histology. There were no significant differences in fractional area change and aortic valve area between groups. In conclusion, echocardiographic cIB was able to quantitatively assess a reduction in CAVD by R-568 in a rat model of CKD. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  18. Protection against vascular endothelial dysfunction by polyphenols in sea buckthorn berries in rats with hyperlipidemia.

    Science.gov (United States)

    Yang, Fang; Suo, Yourui; Chen, Dongli; Tong, Li

    2016-07-19

    Chronic hyperlipemia increases the incidence of vascular endothelial dysfunction and can even induce cardiovascular disease. Sea buckthorn contains a host of bioactives such as flavonoids and polyphenols that can prevent the development of cardiovascular disease. The current study isolated active ingredients, polyphenols, from sea buckthorn berries (SVP) and orally administered SVP at a dose of 7-28 mg/kg. This treatment significantly reduced serum lipids, it enhanced the activity of antioxidant enzymes, and it decreased the level of serum TNF-α and IL-6. SVP also alleviate vascular impairment by decreasing the expression of eNOS, ICAM-1, and LOX-1 mRNA and proteins in aortas of rats with hyperlipidemia. Based on these findings, SVP has antioxidant action and it protects endothelium.

  19. Aortic dissection

    Science.gov (United States)

    ... made in the chest or abdomen. Endovascular aortic repair. This surgery is done without any major surgical ... needed. If the heart arteries are involved, a coronary bypass is also performed. Outlook ... aneurysm - dissecting; Chest pain - aortic dissection; Thoracic aortic aneurysm - ...

  20. Survey the effects of dietary sodium nitrite on the histological changes of the aortic artery in the adult male rats

    Directory of Open Access Journals (Sweden)

    Saeaid Khatamsaz

    2016-05-01

    Full Text Available Background: Because of high consumption of nitrite in processed (fast foods and high level of nitrite in water, soil and ecosystem, nitrite can endanger humans health. In this study the effects of sodium nitrite on aorta was examined in adult male rats. Materials and Methods : In the present study, 30 Wistar adult male rats were randomly divided into three groups of 10, including; control group. First experimental group that received low dose of sodium nitrite (175 mg/kg.bw, second experimental group that received high dose of sodium nitrite (350 mg/kg.bw. They were examined for 60 days. The rats got sodium nitrite through drinking water. At the end of the experiment the rats were taken to the anesthesia jar and based on ether principles, they anesthetized with ether and their blood samples were collected from their hearts. Then their aorta were extracted from their bodies and the tissue sections were prepared for testing tissue changes. Features such as histological features of aorta (morphometric and morphologic features were analyzed. The samples were stained with masson trichrome and Hematoxylin- Eosin methods. The internal media layer was measured with Image tool software. Then the amount of nitrite oxide in their blood were tested. At the end results were analyzed by 17 version of SPSS software and ANOVA test was run. Results: The results of this study showed that thickness of medial layer in two experimental group that received low and high dose of sodium nitrite compared with the control group decreased (p 0.05, and the group that received of high dose of sodium nitrite showed irregular and non- uniform state in aortic media layer. Conclusion: The finding of this study indicated that consumption of sodium nitrite in long term can induce damage in artries tissue.

  1. Blockage of the renin-angiotensin system attenuates mortality but not vascular calcification in uremic rats: sevelamer carbonate prevents vascular calcification.

    Science.gov (United States)

    Tokumoto, Masanori; Mizobuchi, Masahide; Finch, Jane L; Nakamura, Hironori; Martin, Daniel R; Slatopolsky, Eduardo

    2009-01-01

    Hyperphosphatemia is associated with vascular calcification and increased cardiovascular morbidity and mortality. Angiotensin-converting enzyme inhibitors are beneficial in suppressing the progression of kidney and cardiovascular disease. The present studies explore the influence of enalapril and sevelamer carbonate on renal function, vascular calcification and mortality in long-term experimental uremia. Normal and 5/6 nephrectomized rats were fed a high-phosphorus diet for 4 months and treated with enalapril or the combination of both enalapril and sevelamer carbonate. The rats treated with enalapril alone or both enalapril and sevelamer had less deterioration in renal function compared to uremic control as seen by lower serum creatinine (1.6, 1.6 vs. 2.1 mg/dl, respectively, p hyperparathyroidism or vascular calcification. Combination therapy with both enalapril and sevelamer carbonate ameliorated secondary hyperparathyroidism and vascular calcification (calcium content: 854 +/- 40 vs. 1,735 +/- 479 microg/g wet tissue) compared to uremic controls. In these experiments, animal mortality and myocardial hypertrophy were significantly reduced by both enalapril alone and enalapril in combination with sevelamer. In addition, sevelamer carbonate induced beneficial effects on renal dysfunction, secondary hyperparathyroidism and vascular calcification. (c) 2009 S. Karger AG, Basel.

  2. Propionic and butyric acids, formed in the caecum of rats fed highly fermentable dietary fibre, are reflected in portal and aortic serum.

    Science.gov (United States)

    Jakobsdottir, Greta; Jädert, Cecilia; Holm, Lena; Nyman, Margareta E

    2013-11-14

    SCFA are important end products formed during colonic fermentation of dietary fibre (DF). It has been suggested that propionic and butyric acids affect metabolic parameters, low-grade systemic inflammation, insulin resistance and obesity. The aim of the present study was to investigate whether the various SCFA profiles observed after fermentation in the caecum of rats fed pectin, guar gum and fructo-oligosaccharides (FOS) were also represented in hepatic portal and aortic serum. The SCFA in serum were extracted using hollow fibre-supported liquid membrane extraction before GLC analysis. The concentrations of acetic, propionic and butyric acids in caecal content correlated well with those in portal serum (Pacids between the caecal content and aortic serum (Pacid concentration in caecal content was also reflected in the aortic serum (P= 0·019) of rats fed FOS. FOS gave rather low amounts of the SCFA, especially butyric acid, but caecal tissue weight was higher with FOS than with the other two diets. This may be explained by rapid fermentation and quick utilisation/absorption of the SCFA. The present study also showed that propionic acid was metabolised/utilised to a higher extent than butyric acid by colonocytes before reaching the liver. We conclude that the formation of propionic and butyric acids in the caecum is reflected by increased concentrations in the aortic blood. This approach may therefore simplify the evaluation and study of SCFA from DF in human subjects.

  3. Vascular endothelial growth factor blockade alters magnetic resonance imaging biomarkers of vascular function and decreases barrier permeability in a rat model of lung cancer brain metastasis.

    Science.gov (United States)

    Pishko, Gregory L; Muldoon, Leslie L; Pagel, Michael A; Schwartz, Daniel L; Neuwelt, Edward A

    2015-02-17

    Blockade of vascular endothelial growth factor (VEGF) to promote vascular normalization and inhibit angiogenesis has been proposed for the treatment of brain metastases; however, vascular normalization has not been well-characterized in this disease. We investigated the effect of treatment with bevacizumab anti-VEGF antibody on magnetic resonance imaging (MRI) biomarkers of brain tumor vascular characteristics in comparison to small molecule delivery in a rat model of human lung cancer brain metastasis. Athymic rats with A549 human lung adenocarcinoma intracerebral xenografts underwent MRI at 11.75 T before and one day after treatment with bevacizumab (n = 8) or saline control (n = 8) to evaluate tumor volume, free water content (edema), blood volume and vascular permeability (Ktrans). One day later, permeability to 14C-aminoisobutyric acid (AIB) was measured in tumor and brain to assess the penetration of a small drug-like molecule. In saline control animals, tumor volume, edema and permeability increased over the two day assessment period. Compared to controls, bevacizumab treatment slowed the rate of tumor growth (P = 0.003) and blocked the increase in edema (P = 0.033), but did not alter tumor blood volume. Bevacizumab also significantly reduced Ktrans (P = 0.033) and AIB passive permeability in tumor (P = 0.04), but not to peritumoral tissue or normal brain. Post-treatment Ktrans correlated with AIB levels in the bevacizumab-treated rats but not in the saline controls. The correlation of an MRI biomarker for decreased vascular permeability with decreased AIB concentration in tumor after antiangiogenic treatment suggests that bevacizumab partially restored the normal low permeability characteristics of the blood-brain barrier in a model of human lung cancer brain metastasis.

  4. Gastrodin improves cognitive dysfunction and decreases oxidative stress in vascular dementia rats induced by chronic ischemia.

    Science.gov (United States)

    Li, Yang; Zhang, Zhenxing

    2015-01-01

    To study the potential protective effects of gastrodin on reducing tissue oxidative stress and attenuating cognitive deficits in vascular dementia induced by cerebral chronic hyperfusion. To explore the detailed molecular mechanisms. 6 to 8 week old male Wistar rats were adopted as experimental animals. Animals were divided into the following groups: Group 1 (sham group with no occlusion), Group 2 (control group with 2VO procedure), Group 3 (sham group with gastrodin administration), Group 4 (2VO group with gastrodin administration). Morris water maze (MWM) test was adopted to test the learning and memory function of rats within different groups. MDA, glutathione peroxidase and total thiol assessment was done to reflect the oxidative stress in the brain tissue. Cell counting kit-8 (CCK8) and flow cytometry (FCM) were performed to examine the cell viability and apoptosis rate of SH-SY5Y cells induced by hydrogen peroxide and rescued by gastrodin treatments. Reactive oxygen species (ROS) generation was determined by the 2', 7'-dichlorofluorescein diacetate (DCFH-DA) assay. qPCR and Western blot (WB) were adopted to detect the molecular mechanisms related to the anti-apoptosis and ROS scavenging effects of gastrodin. Our results indicated an obvious protective effect of gastrodin on vascular dementia induced brain ischemia. Administration of gastrodin could improve the impaired learning and memory function induced by 2VO procedure in rats. The levels of MDA were partially decreased by the administration of gastrodin. The levels of glutathione peroxidase and total thiol were partially restored by the administration of gastrodin. Cell viability was improved by gastrodin in a dose-dependent pattern on SH-SY5Y cells induced by hydrogen peroxide (P vascular dementia induced oxidative stress due to brain ischemia. On the molecular level, NFE2L2, ADH7, GPX2 and GPX3 were up regulated by gastrodin.

  5. Early treatment with losartan effectively ameliorates hypertension and improves vascular remodeling and function in a prehypertensive rat model.

    Science.gov (United States)

    He, De-Hua; Lin, Jin-Xiu; Zhang, Liang-Min; Xu, Chang-Sheng; Xie, Qiang

    2017-03-15

    Pharmacological treatment of prehypertension may ameliorate hypertension and improve vascular structure and function. This study investigated 1) whether early treatment with either losartan or amlodipine at the onset of prehypertension can prevent hypertension and 2) whether losartan and amlodipine equally improve vascular remodeling and function in a rat model of hypertension. Stroke-prone spontaneously hypertensive (SHRSP) rats were administered losartan, amlodipine or saline for 6 or 16weeks at the onset of prehypertension. Wistar-Kyoto rats were used as a control. All groups were observed for 40weeks. Systolic blood pressure was measured using the tail-cuff method. Vascular structure and function were determined by microscopy and vascular ring contractility assays, respectively. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassays. Angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression was measured by western blot. Losartan effectively reduced progression from prehypertension to hypertension as well as vascular remodeling and improved vascular contractility in SHRSP rats. Long-term losartan (16weeks) had greater benefits than short-term (6weeks) treatment. Losartan increased Ang II and decreased Aldo levels in the serum and vessel walls of resistance vessels in a time-dependent manner. Losartan significantly decreased AT1R and increased AT2R vascular expression. Amlodipine had no effect on vascular AT1R and AT2R expression. Losartan administered at the onset of prehypertension is more effective than amlodipine in ameliorating hypertension and improving vascular remodeling and function, which is likely mediated by the renin-angiotensin-aldosterone system. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Effects of finasteride on the vascular surface density, number of microvessels and vascular endothelial growth factor expression of the rat prostate.

    Science.gov (United States)

    Canda, A Erdem; Mungan, M Ugur; Yilmaz, Osman; Yorukoglu, Kutsal; Tuzel, Emre; Kirkali, Ziya

    2006-01-01

    Finasteride is a 5-alpha-reductase inhibitor used in the medical treatment of benign prostatic hyperplasia (BPH) and appears to be effective in treating prostatic bleeding secondary to BPH. The exact mechanism of this effect is not known. The aim of this study was to evaluate the effects of finasteride on the vascular surface density (VSD), number of microvessels (NVES) and vascular endothelial growth factor (VEGF) expression of the rat prostate. Nineteen adult male rats were used. Finasteride was given to 14, and there were 5 in the control group. Finasteride 80 mg/kg was administered daily via orogastric tube as a suspension for three months. Rats were sacrificed and vascular structures of the prostates were labelled immunohistochemically using CD31 antibodies. VSD and NVES of the prostates were assessed by means of a peroxidase labeled streptavidin-biotin method. VEGF expression was examined by immunohistochemistry using VEGF monoclonal antibody. Mean prostatic weights were decreased significantly in rats given finasteride (p=0.0001). Although an increase in VSD was detected in the finasteride group it was not significant (p=0.26). NVES was significantly increased in the finasteride group (p=0.033). No significant difference was detected between the two groups in terms of VEGF expression (p=0.48). Finasteride does not seem to decrease VSD, NVES and VEGF expression at the level of the rat prostate. The effect of reduction of bleeding in BPH is likely to be due to its effect on shrinking glandular hyperplasia which might enhance vessel wall stability rather than decreasing overall vascularity.

  7. Porphyromonas gingivalis participates in pathogenesis of human abdominal aortic aneurysm by neutrophil activation. Proof of concept in rats.

    Directory of Open Access Journals (Sweden)

    Sandrine Delbosc

    Full Text Available BACKGROUND: Abdominal Aortic Aneurysms (AAAs represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. We postulated that neutrophil recruitment and activation participating in AAA growth may originate in part from repeated episodes of periodontal bacteremia. METHODS AND FINDINGS: Our results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. Human AAA samples were shown to contain bacterial DNA with high frequency (11/16, and in particular that of Porphyromonas gingivalis (Pg, the most prevalent pathogen involved in chronic periodontitis, a common form of periodontal disease. Both DNA reflecting the presence of NETs and antibodies to Pg were found to be increased in plasma of patients with AAA. Using a rat model of AAA, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed. CONCLUSIONS: Thus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression.

  8. Effects of Mild Blast Traumatic Brain Injury on Cerebral Vascular, Histopathological, and Behavioral Outcomes in Rats.

    Science.gov (United States)

    Rodriguez, Uylissa A; Zeng, Yaping; Deyo, Donald; Parsley, Margaret A; Hawkins, Bridget E; Prough, Donald S; DeWitt, Douglas S

    2017-12-20

    To determine the effects of mild blast-induced traumatic brain injury (bTBI), several groups of rats were subjected to blast injury or sham injury in a compressed air-driven shock tube. The effects of bTBI on relative cerebral perfusion (laser Doppler flowmetry [LDF]), and mean arterial blood pressure (MAP) cerebral vascular resistance were measured for 2 h post-bTBI. Dilator responses to reduced intravascular pressure were measured in isolated middle cerebral arterial (MCA) segments, ex vivo, 30 and 60 min post-bTBI. Neuronal injury was assessed (Fluoro-Jade C [FJC]) 24 and 48 h post-bTBI. Neurological outcomes (beam balance and walking tests) and working memory (Morris water maze [MWM]) were assessed 2 weeks post-bTBI. Because impact TBI (i.e., non-blast TBI) is often associated with reduced cerebral perfusion and impaired cerebrovascular function in part because of the generation of reactive oxygen and nitrogen species such as peroxynitrite (ONOO-), the effects of the administration of the ONOO- scavenger, penicillamine methyl ester (PenME), on cerebral perfusion and cerebral vascular resistance were measured for 2 h post-bTBI. Mild bTBI resulted in reduced relative cerebral perfusion and MCA dilator responses to reduced intravascular pressure, increases in cerebral vascular resistance and in the numbers of FJC-positive cells in the brain, and significantly impaired working memory. PenME administration resulted in significant reductions in cerebral vascular resistance and a trend toward increased cerebral perfusion, suggesting that ONOO- may contribute to blast-induced cerebral vascular dysfunction.

  9. Increased transient receptor potential canonical type 3 channels in vasculature from hypertensive rats

    DEFF Research Database (Denmark)

    Liu, Daoyan; Yang, Dachun; He, Hongbo

    2009-01-01

    We tested the hypothesis that transient receptor potential canonical type 3 (TRPC3) channels are increased in vascular smooth muscle cells and aortic tissue from spontaneously hypertensive rats (SHR) compared with normotensive Wistar Kyoto rats. Expression of TRPC3 was analyzed by immunohistochem...

  10. Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model.

    Science.gov (United States)

    Chen, Yu-Cai; Yuan, Tian-Yi; Zhang, Hui-Fang; Wang, Dan-Shu; Yan, Yu; Niu, Zi-Ran; Lin, Yi-Huang; Fang, Lian-Hua; Du, Guan-Hua

    2016-06-01

    The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms. PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg/kg, sc). The rats were orally treated with either SAA (0.3, 1, 3 mg·kg(-1)·d(-1)) or a positive control bosentan (30 mg·kg(-1)·d(-1)) for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and lungs were harvested, the organ indices and pulmonary artery wall thickness were calculated, and biochemical and histochemical analysis were conducted. The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting. Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury and collagen deposition in the lungs. Moreover, the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs. The treatments partially restored MCT-induced reductions of bone morphogenetic protein type II receptor (BMPRII) and phosphorylated Smad1/5 in the lungs. SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis. Thus, SAA may have therapeutic potential for the patients at high risk of PAH.

  11. Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Tharciano Luiz Teixeira Braga da Silva

    2015-01-01

    Full Text Available Abstract Background: Hypertension is a public health problem and increases the incidence of cardiovascular diseases. Objective: To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME-induced hypertensive rats. Methods: Wistar rats were divided into three groups: control (C, hypertensive (H, and exercised hypertensive (EH. Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN, potassium chloride (KCl and sodium nitroprusside (SNP. Results: Rats treated with L-NAME showed an increase (p < 0.001 in systolic blood pressure (SBP, diastolic blood pressure (DBP and mean arterial pressure (MAP compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001 the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01 smooth muscle sensitivity to NPS was observed in group EH as compared to group H. Conclusion: One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

  12. Impact of magnesium:calcium ratio on calcification of the aortic wall.

    Science.gov (United States)

    Villa-Bellosta, Ricardo

    2017-01-01

    An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio.

  13. Effects of Shuangdanmingmu capsule on retinal vascular morphology and VEGF expression in rats with diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Yu-Hui Qin

    2015-01-01

    Full Text Available AIM: To observe the effects of Shuangdanmingmu capsule on VEGF expression and retinal vascular morphology in rats with diabetic retinopathy(DR. METHODS: DR rats were fed with Shuangdanmingmu capsule. By comparing with the normal group, the model control group, and positive control group, the effect of Shuangdanmingmu capsule on retinal tissue of DR rats was observed under electron microscopy. After HE staining, retinal structure was observed under the light microscope. Immunohitochemical staining was used to detect the VEGF expression in retina.RESULTS:Two months after treatment, the layers tissue of retina presented mild edema, capillary pericytes performed edema, mitochondria showed mild swelling and less clear structure, some endothelial cells showed slight proliferation in Shuangdanmingmu group. Compared with the normal group, the expression level of VEGF in retina increased in the other groups, especially in model control group. A significant differential in expression of VEGF was found between Shuangdanmingmu group, positive control group and model control group(PCONCLUSION: Shuangdanmingmu capsule can effectively improve the retinal microvascular, reduce edema and necrosis of each layer of retina, improve the ultrastructure of retina's tissue and inhibit VEGF expression in DR rats.

  14. Simvastatin Combined with Antioxidant Attenuates the Cerebral Vascular Endothelial Inflammatory Response in a Rat Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Kuo-Wei Wang

    2014-01-01

    Full Text Available Traumatic brain injury (TBI leads to important and deleterious neuroinflammation, as evidenced by indicators such as edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation. In our previous study, we proved that simvastatin could attenuate cerebral vascular endothelial inflammatory response in a rat traumatic brain injury. This purpose of this study was to determine whether simvastatin combined with an antioxidant could produce the same effect or greater and to examine affected surrogate biomarkers for the neuroinflammation after traumatic brain injury in rat. In our study, cortical contusions were induced, and the effect of acute and continuous treatment of simvastatin and vitamin C on behavior and inflammation in adult rats following experimental TBI was evaluated. The results demonstrated that simvastatin combined with an antioxidant could provide neuroprotection and it may be attributed to a dampening of cerebral vascular endothelial inflammatory response.

  15. Etelcalcetide, A Novel Calcimimetic, Prevents Vascular Calcification in A Rat Model of Renal Insufficiency with Secondary Hyperparathyroidism

    OpenAIRE

    Yu, Longchuan; Tomlinson, James E.; Alexander, Shawn T.; Hensley, Kelly; Han, Chun-Ya; Dwyer, Denise; Stolina, Marina; Dean, Charles; Goodman, William G.; Richards, William G.; Li, Xiaodong

    2017-01-01

    Etelcalcetide, a novel peptide agonist of the calcium-sensing receptor, prevents vascular calcification in a rat model of renal insufficiency with secondary hyperparathyroidism. Vascular calcification occurs frequently in patients with chronic kidney disease (CKD) and is a consequence of impaired mineral homeostasis and secondary hyperparathyroidism (SHPT). Etelcalcetide substantially lowers parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) levels in SHPT patients on hemodialy...

  16. Ellagic acid inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and prevents atheroma formation in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Rani, Uma P; Kesavan, Rushendhiran; Ganugula, Raghu; Avaneesh, T; Kumar, Uday P; Reddy, G Bhanuprakash; Dixit, Madhulika

    2013-11-01

    Plant-derived polyphenolic compounds have beneficial health effects. In the present study, we determined the ability of ellagic acid (EA) to prevent platelet-derived growth factor-BB (PDGF-BB)-induced proliferation of primary cultures of rat aortic smooth muscle cells (RASMCs). We also determined the ability of EA to prevent atherosclerosis in streptozotocin-induced diabetic rats. Proliferation of cells was measured via Alamar Blue assay and through propidium iodide-based cell cycle analysis in flow cytometer. Reactive oxygen species (ROS) were measured via 2',7'-dichlorofluorescin diacetate and Amplex red methods. Expression of proliferation markers and activation of kinases were assessed by immunoblot analysis. Cotreatment of primary cultures of RASMCs with 25 μmol/L of EA significantly reduced PDGF-BB (20 ng/ml)-induced proliferation by blocking S-phase entry. EA effectively blocked PDGF receptor-β (PDGFR-β) tyrosine phosphorylation, generation of intracellular ROS and downstream activation of extracellular signal-regulated kinase 1/2. It also blocked PDGF-BB-induced expression of cyclin D1. Computational molecular docking of EA with the PDGFR-β-PDGF-BB complex revealed two putative inhibitor binding sites which showed similar binding energies with the known PDGFR-β inhibitor AG1295. In diabetic rats, supplementation of diet with 2% EA significantly blocked diabetes-induced medial thickness, and lipid and collagen deposition in the arch of aorta. These were assessed through haematoxylin and eosin, Oil Red O and Masson's trichome staining, respectively. EA treatment also blocked cyclin D1 expression in medial smooth muscle cells in experimental animals. Thus, EA is effective in reducing atherosclerotic process by blocking proliferation of vascular smooth muscle cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Effect of Cymbopogon citratus and Citral on Vascular Smooth Muscle of the Isolated Thoracic Rat Aorta.

    Science.gov (United States)

    Devi, R Chitra; Sim, S M; Ismail, R

    2012-01-01

    Cymbopogon citratus has been shown to have antioxidant, antimicrobial, antispasmodic and chemo-protective properties. Citral, is the major constituent of C. citratus. This study investigated the effects of methanolic extracts of leaves (LE), stems (SE), and roots (RE) of C. citratus and citral on vascular smooth muscle and explored their possible mechanisms of action. The experiment was conducted using isolated tissue preparations, where citral, LE, SE, and RE were added separately into a tissue bath that contained aortic rings, which were pre-contracted with phenylephrine (PE). Citral, LE, and RE exhibited a dose-dependent relaxant effect on the PE-induced contractions. Citral appeared to partially act via NO as its vasorelaxant effect was attenuated by L-NAME. However, the effect of LE may involve prostacyclin as indomethacin reversed the relaxant effect of LE on the PE-induced contraction. Furthermore, citral, LE, and RE abolished the restoration of PE-induced contraction caused by the addition of increasing doses of calcium in both endothelium intact and denuded rings. These findings suggest that the relaxation effect of citral, LE, and RE is endothelium-independent and may be mainly by affecting the intracellular concentration of calcium. Citral may partially act through the NO pathway while a vasodilator prostaglandin may mediate the effect of LE.

  18. [The effect of hydrogen sulfide on contractile activity of the vascular smooth muscles in rats].

    Science.gov (United States)

    Semenykhina, O M; Baziliuk, O V; Korkach, Iu P; Sahach, V F

    2011-01-01

    The effect of endogenous and exogenous hydrogen sulfide (H2S) on contractile activity of vascular smooth muscle (VSM) was studied. The introduction of substrate synthesis H2S L-cysteine and its donor NaHS in vitro caused concentration-dependent relaxation of VSM of aorta and portal vein. Low concentrations of hydrogen sulfide donor (10(-5) mol/L) caused vasoconstriction of both types of the vessels. It was shown that the reaction of relaxation of VSM in response to NaHS is independent from endothelium. It was revealed that VSM of portal vein are more sensitive to the effects of H2S than VSM of aorta. Removing of aorta periadventitial adipose tissue showed no relaxation reply to the hydrogen sulfide donor NaHS in 70% of experiments. Some of the cellular mechanisms of hydrogen sulfide action were established, namely relaxation of aorta is depended on K(ATP) channel activation. This is manifested by a lack of relaxation of the aortic VSM due to K(ATP) channel inhibitor glibenclamide.

  19. Tetramethylpyrazine Enhances Vascularization and Prevents Osteonecrosis in Steroid-Treated Rats

    Directory of Open Access Journals (Sweden)

    Yini Jiang

    2015-01-01

    Full Text Available Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH is an avascular necrosis disease of bone. Tetramethylpyrazine (TMP, with significant vascular protective properties, has been widely used for the treatments of ischemic neural disorders and cardiovascular diseases. However, its role in the treatment of steroid-induced ONFH has not been evaluated. In this study, our results showed that TMP significantly decreased the ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in steroid-induced ONFH rats histopathologically. TMP also reduced the levels of serum lipid dramatically by haematological examination. According to the micro-CT quantification, TMP could improve the microstructure of the trabecular bone and increases bone mineral density in steroid-induced ONFH rats. Moreover, TMP significantly increased the vessel volume, vessel surface, percentage of vessel volume, and vessel thickness of the femoral heads by micro-CT. Interestingly, the downregulation of VEGF and FLK1 proteins in the sera and necrotic femoral heads could be reversed by TMP treatment, and this was true for their mRNA expressions in femoral heads. In conclusion, these findings suggest for the first time that TMP may prevent steroid-induced ONFH and also enhance femoral head vascularization by inhibiting the effect of steroid on VEGF/FLK1 signal pathway.

  20. Topical administration of Metamizole and its implications on vascular reactivity in Wistar rats- Experimental research

    Science.gov (United States)

    Coman, Ioana-Cristina; Paunescu, Horia; Stamate, Alina Cristina; Cherecheanu, Alina Popa; Ghita, Isabel; Barac, Cosmina; Vasile, Danut; Tudosescu, Ruxandra; Fulga, Ion

    2017-01-01

    Aim: The aim of this paper was to describe the possible implications of topical (ocular) administration of Metamizole on vascular reactivity of the iris in Wistar rats. No other study regarding its topical use was found. Methods: Male adult Wistar rats were anaesthetized with Ketamine 100 mg /kg body weight - injected intraperitoneally - while maintaining spontaneous respiration and the blink reflex. After selecting the area of interest (long posterior ciliary artery – LPCA), manual adjustments of the image magnitude, clarity, and brightness were made, and the experiment began. The image recording lasted 10 minutes. Results: Metamizole induced a slight vasoconstriction that started with the initial moment for all the doses used. After the topical administration of Metamizole, we did not observe an increase of the vascular diameter of LPCA in a dose dependent manner. The saline solution used as a negative control did not modify the vessel diameter. Conclusions: Metamizole (dipyrone) is a non-opioid drug, which is commonly used in human and veterinary medicine. It is the most popular first-line analgesic in various populations. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug. The high analgesic efficacy of metamizole, as well as its spasmolytic effect, makes it a very important pharmaceutical agent that could be used in the therapy of various eye disorders in humans and in animals. Abbreviations: COX = Cyclooxygenase; LPCA = Long Posterior Ciliary Artery; PRP = panretinal photocoagulation; PDR = proliferative diabetic retinopathy; Sec = second(s); VSPR = very severe non proliferative diabetic retinopathy

  1. Imaging separation of neuronal from vascular effects of cocaine on rat cortical brain in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Z.; Du, C.; Yuan, Z.; Luo, Z.; Volkow, N.D.; Pan, Y.; Du, C.

    2010-09-08

    MRI techniques to study brain function assume coupling between neuronal activity, metabolism and flow. However, recent evidence of physiological uncoupling between neuronal and cerebrovascular events highlights the need for methods to simultaneously measure these three properties. We report a multimodality optical approach that integrates dual-wavelength laser speckle imaging (measures changes in blood flow, blood volume and hemoglobin oxygenation), digital-frequency-ramping optical coherence tomography (images quantitative 3D vascular network) and Rhod2 fluorescence (images intracellular calcium for measure of neuronal activity) at high spatiotemporal resolutions (30 {micro}m, 10 Hz) and over a large field of view (3 x 5 mm{sup 2}). We apply it to assess cocaine's effects in rat cortical brain and show an immediate decrease 3.5 {+-} 0.9 min, phase (1) in the oxygen content of hemoglobin and the cerebral blood flow followed by an overshoot 7.1 {+-} 0.2 min, phase (2) lasting over 20 min whereas Ca{sup 2+} increased immediately (peaked at t = 4.1 {+-} 0.4 min) and remained elevated. This enabled us to identify a delay (2.9 {+-} 0.5 min) between peak neuronal and vascular responses in phase 2. The ability of this multimodality optical approach for simultaneous imaging at high spatiotemporal resolutions permits us to distinguish the vascular versus cellular changes of the brain, thus complimenting other neuroimaging modalities for brain functional studies (e. g., PET, fMRI).

  2. Impaired vascular contractility and aortic wall degeneration in fibulin-4 deficient mice: effect of angiotensin II type 1 (AT1 receptor blockade.

    Directory of Open Access Journals (Sweden)

    Els Moltzer

    Full Text Available Medial degeneration is a key feature of aneurysm disease and aortic dissection. In a murine aneurysm model we investigated the structural and functional characteristics of aortic wall degeneration in adult fibulin-4 deficient mice and the potential therapeutic role of the angiotensin (Ang II type 1 (AT(1 receptor antagonist losartan in preventing aortic media degeneration. Adult mice with 2-fold (heterozygous Fibulin-4(+/R and 4-fold (homozygous Fibulin-4(R/R reduced expression of fibulin-4 displayed the histological features of cystic media degeneration as found in patients with aneurysm or dissection, including elastin fiber fragmentation, loss of smooth muscle cells, and deposition of ground substance in the extracellular matrix of the aortic media. The aortic contractile capacity, determined by isometric force measurements, was diminished, and was associated with dysregulation of contractile genes as shown by aortic transcriptome analysis. These structural and functional alterations were accompanied by upregulation of TGF-β signaling in aortas from fibulin-4 deficient mice, as identified by genome-scaled network analysis as well as by immunohistochemical staining for phosphorylated Smad2, an intracellular mediator of TGF-β. Tissue levels of Ang II, a regulator of TGF-β signaling, were increased. Prenatal treatment with the AT(1 receptor antagonist losartan, which blunts TGF-β signaling, prevented elastic fiber fragmentation in the aortic media of newborn Fibulin-4(R/R mice. Postnatal losartan treatment reduced haemodynamic stress and improved lifespan of homozygous knockdown fibulin-4 animals, but did not affect aortic vessel wall structure. In conclusion, the AT(1 receptor blocker losartan can prevent aortic media degeneration in a non-Marfan syndrome aneurysm mouse model. In established aortic aneurysms, losartan does not affect aortic architecture, but does improve survival. These findings may extend the potential therapeutic

  3. Aortic stenosis

    Science.gov (United States)

    ... but most often it develops later in life. Children with aortic stenosis may have other conditions present from birth. Aortic ... children may need aortic valve repair or replacement. Children with mild aortic stenosis may be able to take part in most ...

  4. Transcatheter valve-in-valve implantation due to severe aortic regurgitation in a degenerated aortic homograft

    DEFF Research Database (Denmark)

    Olsen, Lene Kjaer; Engstrøm, Thomas; Søndergaard, Lars

    2009-01-01

    a successful valve-in-valve implantation of a CoreValve aortic valve prosthesis through the right subclavian artery in a case of severe aortic regurgitation within a degenerated aortic homograft. The case exemplifies the possibilities of expanding the indications for TAVI, as well as other vascular access...

  5. Losartan reverses COX-2-dependent vascular dysfunction in offspring of hyperglycaemic rats.

    Science.gov (United States)

    de Queiroz, Diego Barbosa; Ramos-Alves, Fernanda Elizabethe; Santos-Rocha, Juliana; Duarte, Gloria Pinto; Xavier, Fabiano Elias

    2017-09-01

    This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT1R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day-1) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements. COX-2 expression was analyzed by Western blot; TxA2, PGE2 and PGF2α release was measured using commercial kits. O-DR showed increased blood pressure, impaired acetylcholine-induced vasodilation and increased noradrenaline-induced vasoconstriction than O-CR. All these parameters were normalized by losartan in O-DR. Pre-incubation of MRA with indomethacin (COX-1/2 inhibitor), NS-398 (COX-2 inhibitor) or tempol (superoxide dismutase mimetic) increased relaxation to acetylcholine and reduced contraction to noradrenaline only in O-DR. COX-2 expression, TxA2, PGE2 and PGF2α release were increased in O-DR. In losartan-treated O-DR, NS-398, indomethacin or tempol failed to produce any effect on acetylcholine or noradrenaline responses. Losartan treatment reduced COX-2 expression, TxA2, PGE2 and PGF2α release in O-DR. The present results reveal that chronic losartan administration in O-DR normalizes endothelial function in MRA by correcting the existing COX-2 overexpression and the imbalance between endothelium-derived relaxing and contracting factors. These findings not only support the beneficial effects of AT1 receptor antagonist in O-DR, but also suggest the implication of angiotensin II as a putative mediator of hyperglycemia-programmed vascular dysfunction in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Chronic binge alcohol exposure during pregnancy impairs rat maternal uterine vascular function.

    Science.gov (United States)

    Subramanian, Kaviarasan; Naik, Vishal D; Sathishkumar, Kunju; Yallampalli, Chandrashekar; Saade, George R; Hankins, Gary D; Ramadoss, Jayanth

    2014-07-01

    Alcohol exposure during pregnancy results in an array of structural and functional abnormalities called fetal alcohol spectrum disorders (FASD). Alcohol dysregulates the exquisite coordination and regulation of gestational adaptations at the level of the uterine vasculature. We herein hypothesized that chronic binge-like alcohol results in uterine vascular dysfunction and impairs maternal uterine artery reactivity to vasoconstrictors and dilators. We utilized a once-daily binge alcohol (4.5 g/kg body weight) exposure paradigm (gestational day 7 to 17) in a pregnant rat model system and investigated primary uterine artery function in response to vasoconstrictors and vasodilators utilizing wire myography. Alcohol (peak blood alcohol concentration, 216 mg/dl) produced uterine vascular dysfunction. Alcohol did not produce altered uterine vascular reactivity to α1 adrenergic agonist phenylephrine or the prostanoid thromboxane. However, alcohol specifically impaired acetylcholine (ACh)-mediated uterine artery vasodilation but exogenous endothelium-independent vasodilators like sodium nitroprusside exhibited no alcohol effect; ACh significantly decreased vessel relaxation (p = 0.003; ↓pD2 [negative log molar ACh concentration producing the half maximum response], -7.004 ± 0.215 vs. -6.310 ± 0.208; EMax [maximal ACh response], 92% vs. 75%). We conclude that moderate alcohol exposure impairs uterine vascular function in pregnant mothers. Alcohol specifically impairs agonist-induced uterine artery vasodilation. In summary, the maternal uterine compartment may play a significant role in the pathogenesis of FASD. Thus, the mechanistic targets of alcohol at the level of both the mother and the fetus need to be considered in order to develop effective therapeutic treatment strategies for FASD. Copyright © 2014 by the Research Society on Alcoholism.

  7. Dynamic changes of serum vascular endothelial growth factor levels in a rat myocardial infarction model.

    Science.gov (United States)

    Yin, R; Feng, J; Yao, Z

    2000-09-01

    To investigate the dynamic changes of serum vascular endothelial growth factor (VEGF) levels in a rat model of acute myocardial infarction. Eighty-eight adult male Sprague-Dawley rats weighing approximately 270 g we used in this study. Eighty rats were subjected to left coronary artery ligation, with 8 rats for each different duration of infarct. Eight sham-operated animals in which the left coronary artery was surgically exposed without ligation were used as controls. Blood samples were drawn from the right atrium before (sham animals) and 1, 3, 6, 12, 24 h and 2, 3, 5, 7, 14 d after myocardial infarction. The concentrations of serum VEGF were measured by a sensitive enzyme-linked imosorbent assay with a rabbit polyclonal antibody specific for VEGF. In the 8 control animals, the mean concentration of serum VEGF was 66.99 +/- 17.83 pg/ml. Six hours after myocardial infarction, the level of serum VEGF significantly increased to 125.68 +/- 28.07 pg/ml (P < 0.01 vs x sham controls), and reached a peak (240.61 +/- 70.63 pg/ml. P < 0.01 vs x sham animals) at 24 h after ligation and then decreased gradually over the remaining 2 weeks. However, the level remained significantly elevated for 14 d (107.64 +/- 30.13 pg/ml, P < 0.01 vs x sham controls). The present study shows that the levels of serum VEGF are markedly increased until 14 d in the rat model of acute myocardial infarction. The increased serum VEGF level may play an important role in the angiogenesis associated with myocardial infarction.

  8. Tooth bleaching induces changes in the vascular permeability of rat incisor pulps.

    Science.gov (United States)

    Ferreira, Vanessa Guarino; Nabeshima, Cleber Keiti; Marques, Márcia Martins; Paris, Adriana Fraga Costa Samos; Gioso, Marco Antônio; dos Reis, Rodrigo Sant'anna Aguiar; Machado, Manoel Eduardo de Lima

    2013-10-01

    To evaluate the inflammatory response in dental pulps of rat incisors subjected to tooth bleaching protocols with different HP concentrations and application times. 42 incisors from Wistar rats were submitted to tooth bleaching using concentrations of 25% or 35% HP for treatment times of 15, 30 or 45 minutes. Four non-bleached teeth were used as controls. The animals received an intravenous injection of India ink immediately after the bleaching procedure and were sacrificed 1 hour later. Six bleached teeth from each group and three controls were made transparent, and one sample from each group was processed for histological analysis. The data were statistically analyzed using Kruskal Wallis and Dunn's tests (P ink content was significantly higher in the samples that were bleached with 35% HP for 30 minutes and with both HP concentrations (25 and 35%) for 45 minutes than in the controls. For the samples bleached with the same HP concentration, the ink content was higher in samples that were bleached for 45 minutes. These results indicate that HP tooth bleaching can induce an increase in vascular permeability in rat incisors. Importantly, this increase is more dependent on the length of the bleaching procedure than on the concentration of the bleaching agent.

  9. [Experiment study on ultrashort wave for treating vascular crisis after rat tail replantation].

    Science.gov (United States)

    Tan, Long; Gao, Wenshan; Xi, Ali; Wang, Cong; Chen, Shouying; Zhao, Yanyan; Di, Keqian; Yang, Xincai; Weng, Shengbin

    2012-10-01

    To explore the effect and mechanism of ultrashort wave (USW) for prevention and treatment of vascular crisis after rat tail replantation. Eighty 3-month old female Sprague Dawley rats (weighing 232.8-289.6 g) were randomly divided into 5 groups. In each group, based on the caudal vein and the coccyx was retained, the tail was cut off. The tail artery was ligated in group A; the tail artery was anastomosed in groups B, C, D, and E to establish the tail replantation model. After surgery, the rats of group B were given normal management; the rats of group C were immediately given intraperitoneal injection (3.125 mL/kg) of diluted papaverine hydrochloride injection (1 mg/mL); the rats of groups D and E were immediately given the local USW treatment (once a day) at anastomotic site for 5 days at the dosage of 3 files and 50 mA for 20 minutes (group D) and 2 files and 28 mA for 20 minutes (group E). The survival rate of the rat tails was observed for 10 days after the tail replantation. The tail skin temperature difference between proximal and distal anastomosis was measured at pre- and post-operation; the change between postoperative and preoperative temperature difference was calculated. The blood plasma specimens were collected from the inner canthus before operation and from the tip of the tail at 8 hours after operation to measure the content of nitric oxide (NO). The survival rates of the rat tails were 0 (0/14), 36.4% (8/22), 57.1% (8/14), 22.2% (4/18), and 75.0% (9/12) in groups A, B, C, D, and E, respectively, showing significant overall differences among 5 groups (chi2 = 19.935, P = 0.001); the survival rate of group E was significantly higher than that of group B at 7 days (P 0.05). At preoperation, there was no significant difference in tail skin temperature difference among 5 groups (P > 0.05); at 8 hours, 5 days, 6 days, and 7 days after operation, significant overall difference was found in the change of the skin temperature difference among groups (P

  10. [Effect of Yangxue Qingnao Granule on the Expression of CD11b in CA1 Region of Hippocampus of Vascular Dementia Rats].

    Science.gov (United States)

    Li, Jing; Ma, Yuan-yuan; Liu, Bin; Mao, Wen-jing; Zhang, Jin-xia; Li, Shi-ying

    2016-05-01

    To observe the effect of Yangxue Qingnao Granule (YQG) on the expression of CD11b in CA1 region of hippocampus of vascular dementia rats, and to explore its regulation on microglias. Totally 144 SD rats were randomly divided into the sham-operation group, the vascular dementia model group (model), and the YQG treated group (treated). The vascular dementia rat model was prepared by modified Pulsinelli's four-vessel occlusion. Rats in the sham-operation group and the model group were administered with normal saline -(at the daily dose of 10 mL/kg) by gastrogavage, while those in the treated group were administered with YQG (0.32 g/mL, at the daily dose of 10 mL/kg) by gastrogavage. All administration was performed once per day for 8 successive weeks. The expression of CD11b in CA1 region of hippocampus of vascular dementia rats was detected at week 1, 2, 4, and 8, respectively. Compared with the sham-operation group, the expression of CD11b in CA1 region of hippocampus of vascular dementia rats were significantly enhanced in the model group at each time point (P vascular dementia rats significantly decreased in the treated group at each time point (P vascular dementia rats, and YQG could inhibit activation and proliferation of microglias.

  11. Apelin-13 upregulates Egr-1 expression in rat vascular smooth muscle cells through the PI3K/Akt and PKC signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qi-Feng [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Yu, Hong-Wei [Department of Cardiology, Jinzhou Central Hospital, Jinzhou 121001 (China); Sun, Li-Li [Department of Ophthalmology, The Third Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); You, Lu; Tao, Gui-Zhou [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Qu, Bao-Ze, E-mail: qubaoze1971@hotmail.com [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China)

    2015-12-25

    Previous studies have shown that Apelin-13 upregulates early growth response factor-1 (Egr-1) via the extracellular signal-regulated protein kinase (ERK) signaling pathway. Apelin-13 induces proliferation and migration of vascular smooth muscle cells (VSMCs) as well as the upregulation of osteopontin (OPN) via the upregulation of Egr-1. This study was designed to further explore the activity of Apelin-13 in VSMCs by investigating members of the mitogen-activated protein kinase (MAPK) family, in particular Jun kinase (JNK) and p38 mitogen-activated protein kinase (P38). We also examined whether the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) and protein kinase C (PKC) signaling pathways were involved in the regulation of Egr-1 by Apelin-13. We treated rat aortic VSMCs with Apelin-13 and examined the expression of JNK, p-JNK, P38, and p-P38 to investigate whether Apelin-13-mediated increases in Egr-1 occurred through the JNK and P38 signaling pathways. We then pretreated VSMCs with the Gi protein inhibitor pertussis toxin (PTX) and the Gq inhibitor YM254890, added Apelin-13 and looked for changes in Egr-1 expression. Finally, we pretreated with the PI3K inhibitor LY294002 and the PKC inhibitor GF109203X, and treated with Apelin-13. Our results showed that JNK and P38 did not participate in Apelin-13-mediated increase in Egr-1. Instead, Apelin-13 upregulation of Egr-1 was mediated by a PTX-sensitive Gi protein. Apelin-13 did increase ERK phosphorylation through the PI3K/Akt and PKC signaling pathways, resulting in changes in Egr-1 expression. These data provide important targets for future studies to modulate vascular remodeling. - Highlights: • Apelin-13 mediates Egr-1 upregulation in vascular smooth muscle cells via ERK1/2. • The underlying mechanisms are unknown, but exclude Jnk or p38 pathway activation. • Apelin-13 binds to Gi, activating the PI3K/Akt and PKC signaling cascades. • Consequent ERK phosphorylation results in increased Egr-1

  12. Effects of donepezil, an acetylcholinesterase inhibitor, on neurogenesis in a rat model of vascular dementia.

    Science.gov (United States)

    Kwon, Kyoung Ja; Kim, Min Kyeong; Lee, Eun Joo; Kim, Jung Nam; Choi, Bo-Ryoung; Kim, Soo Young; Cho, Kyu Suk; Han, Jung-Soo; Kim, Hahn Young; Shin, Chan Young; Han, Seol-Heui

    2014-12-15

    Vascular dementia (VaD) is the second most common form of dementia caused by cerebrovascular disease. Several recent reports demonstrated that cholinergic deficits are implicated in the pathogenesis of VaD and that cholinergic therapies have shown improvement of cognitive function in patients with VaD. However, the precise mechanisms by which donepezil achieves its effects on VaD are not fully understood. Donepezil hydrochloride is an acetylcholinesterase inhibitor (AChEI) currently used for the symptomatic treatment of Alzheimer's disease (AD). Several lines of evidence have demonstrated that AChEIs such as donepezil promote neurogenesis in the central nervous system. We investigated whether donepezil regulated hippocampal neurogenesis after bilateral common carotid artery occlusion (BCCAO) in rats, a commonly used animal model of VaD. To evaluate the effect of donepezil on neurogenesis, we orally treated rats with donepezil (10mg/kg) once a day for 3weeks, and injected BrdU over the same 3-week period to label newborn cells. The doses of donepezil that we used have been reported to activate cholinergic activity in rats. After 3weeks, a water maze task was performed on these rats to test spatial learning, and a subsequent histopathological evaluation was conducted. Donepezil improved memory impairment and increased the number of BrdU-positive cells in the dentate gyrus (DG) of BCCAO animals. These results indicated that donepezil improves cognitive function and enhances the survival of newborn neurons in the DG in our animal model of VaD, possibly by enhancing the expression of choline acetyltransferase and brain-derived neurotropic factor. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Beneficial Effect of Protein Tyrosine Phosphatase Inhibitor and Phytoestrogen in Dyslipidemia-Induced Vascular Dementia in Ovariectomized Rats.

    Science.gov (United States)

    Verma, Aditi; Sharma, Saurabh

    2015-11-01

    Estrogen deficiency and increase in protein tyrosine phosphatase (PTPase) activity may be a key mechanism in postmenopausal dyslipidemia-induced vascular dysfunction and dementia. Thus, the present study has been designed to investigate the effect of biochanin A (BCA, a phytoestrogen) and sodium orthovanadate (SOV), an inhibitor of PTPase in dyslipidemia-induced vascular dementia in ovariectomized rats. Female Wistar rats were ovariectomized and fed on high fat diet for 4 weeks to produce dyslipidemia. Dyslipidemia was assessed by estimation of serum lipid levels including total cholesterol, triglyceride, HDL, and LDL levels. Dementia was assessed in terms of increase in brain acetylcholinesterase (AChE) activity and attenuation of learning ability (escape latency time) and memory retention (time spent in target quadrant) using Morris water maze. Vascular dysfunction was assessed in terms of attenuation of acetylcholine-induced endothelium-dependent relaxation (isolated carotid ring preparation), mRNA expression of endothelial nitric oxide synthase, and increase in serum thiobarbituric acid reactive species, superoxide anion level. Neurodegeneration was assessed in hippocampus by hematoxylin and eosin staining. BCA (2.5 and 5 mg/kg) and SOV (5 and 10 mg/kg) were administered alone and in low-dose combination to ovariectomized dyslipidemic rats. BCA (2.5 and 5 mg/kg), SOV (5 and 10 mg/kg), and donepezil (1 mg/kg) significantly improves vascular function, and learning and memory ability and decreases the neuronal cell death, oxidative stress, and AChE in ovariectomized dyslipidemic rats. Thus, it may be concluded that BCA and SOV attenuate vascular dysfunction and dementia in dyslipidemic ovariectomized rats. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Effect of chemokine receptor CXCR4 on hypoxia-induced pulmonary hypertension and vascular remodeling in rats

    Directory of Open Access Journals (Sweden)

    Hales Charles A

    2011-02-01

    Full Text Available Abstract Background CXCR4 is the receptor for chemokine CXCL12 and reportedly plays an important role in systemic vascular repair and remodeling, but the role of CXCR4 in development of pulmonary hypertension and vascular remodeling has not been fully understood. Methods In this study we investigated the role of CXCR4 in the development of pulmonary hypertension and vascular remodeling by using a CXCR4 inhibitor AMD3100 and by electroporation of CXCR4 shRNA into bone marrow cells and then transplantation of the bone marrow cells into rats. Results We found that the CXCR4 inhibitor significantly decreased chronic hypoxia-induced pulmonary hypertension and vascular remodeling in rats and, most importantly, we found that the rats that were transplanted with the bone marrow cells electroporated with CXCR4 shRNA had significantly lower mean pulmonary pressure (mPAP, ratio of right ventricular weight to left ventricular plus septal weight (RV/(LV+S and wall thickness of pulmonary artery induced by chronic hypoxia as compared with control rats. Conclusions The hypothesis that CXCR4 is critical in hypoxic pulmonary hypertension in rats has been demonstrated. The present study not only has shown an inhibitory effect caused by systemic inhibition of CXCR4 activity on pulmonary hypertension, but more importantly also has revealed that specific inhibition of the CXCR4 in bone marrow cells can reduce pulmonary hypertension and vascular remodeling via decreasing bone marrow derived cell recruitment to the lung in hypoxia. This study suggests a novel therapeutic approach for pulmonary hypertension by inhibiting bone marrow derived cell recruitment.

  15. The effects of ionizing radiation on the function and vascular structure of the rat submandibular gland

    Energy Technology Data Exchange (ETDEWEB)

    Kawamata, Fumio (Nippon Dental Univ., Tokyo (Japan))

    1991-06-01

    In radiotherapy for the jaw and face, the irradiation field frequently affects the salivary gland, in an aduerse way. In the present study, I assessed the functional influence of radiation on the submandibular gland by RI, with inspection of both the vascular distribution of the submandibular gland by India ink and resin molding methods, and of the histological changes by HE and PAS staining. Each experimental group consisted of 9 male Wistar strain rats aged 8 weeks. Single irradiation was performed at 10 Gy and 50 Gy doses by {sup 60}Co-{gamma} ray. The changes at 6 hours, 3, 7, 14, and 28 days after irradiation were determined and compared with those in the control group. Function tests for uptake and clearance were performed using {sup 99m}TcO{sub 4}{sup -}. Results showed the uptake and clearance value in the irradiation group was higher than that in the control group. With respect to the effect of irradiation on blood vessels, vasodilation, flexion, and destruction of the blood wall were observed. In addition, various histological changes appeared. In each examination, the irradiation effects in the 50 Gy group were greater than those in the 10 Gy group. In conclusion, the decline in submandibular function after 10 Gy and 50 Gy irradiation is related to histological changes in the vascular system and glandular tissues. (author) 63 refs.

  16. Comparison of the vascular innervation of the rat cochlea and vestibular system.

    Science.gov (United States)

    Lyon, M J; Payman, R N

    2000-03-01

    In order to gain a better understanding of the neuronal and local control of inner ear blood flow, the vascular innervation to the rat cochlea and vestibular system was examined. Specimens were removed in toto beginning at the basilar artery extending to the anterior inferior cerebellar artery, labyrinthine artery, common cochlear artery, modiolar artery and anterior vestibular artery. When possible the vessels were dissected in continuity through the cribrose area. The vestibular endorgans were also removed. Specimens were examined using immunohistochemical techniques for the presence of vasoactive intestinal peptide, neuronal nitric oxide synthase, neuropeptide-Y, substance P and calcitonin gene related peptide. Results show that the vasculature to the cochlea and vestibular portion of the inner ear receive similar types of nonadrenergic innervation, that within the vestibular endorgans, only CGRP and SP were found in the neuroepithelium or in association with vessels, and that within the vestibular system, the majority of the vascular innervation appears to stop at or near the cribrose area. In the cochlea however, it extends to include the radiating arterioles. These findings suggest that cochlear blood flow is under finer control and that neuronally induced changes in blood flow may have a more global effect in the vestibular periphery.

  17. Sildenafil limits monocrotaline-induced pulmonary hypertension in rats through suppression of pulmonary vascular remodeling.

    Science.gov (United States)

    Yen, Chia-Hung; Leu, Steve; Lin, Yu-Chun; Kao, Ying-Hsien; Chang, Li-Teh; Chua, Sarah; Fu, Morgan; Wu, Chiung-Jen; Sun, Cheuk-Kwan; Yip, Hon-Kan

    2010-06-01

    We hypothesize that sildenafil attenuates pulmonary hypertension through suppressing pulmonary vascular remodeling. Thirty male adult Sprague-Dawley rats were randomized to receive saline injection (Group 1), subcutaneous monocrotaline (MCT) (60 mg/kg) (Group 2), and MCT plus oral sildenafil (30 g/kg per day) (Group 3) 5 days after MCT administration. By Day 35, Western blot showed lower connexin43 and membranous protein kinase C epsilon expressions but higher oxidative stress in right ventricle in Group 2 compared with the other groups. Additionally, pulmonary Smad1/5 was lowest, whereas connexin43 and Smad3 were highest in Group 2. Pulmonary mRNA expressions of tumor necrosis factor-alpha, caspase-3, plasminogen activator inhibitor-1, and transforming growth factor-beta were higher, whereas bone morphogenetic protein Type II receptor, Bcl-2, and endothelial nitric oxide synthase were lower in Group 2 than in the other groups. Similarly, mRNA expressions of tumor necrosis factor-alpha, caspase-3, and beta-myosin heavy chain were increased, whereas Bcl-2, endothelial nitric oxide synthase, and alpha-myosin heavy chain expressions in right ventricle were reduced in Group 2 compared with the other groups. Number of lung arterioles was lowest, whereas number of arterioles with muscularization of the medial layer was highest in Group 2. Right ventricle systolic pressure and weight were elevated in Group 2 compared with the other groups. In conclusion, sildenafil effectively alleviates MCT-induced pulmonary hypertension through suppressing pulmonary vascular remodeling.

  18. Heat shock protein 70, heat shock protein 32, and vascular endothelial growth factor production and their effects on lipopolysaccharide-induced apoptosis in porcine aortic endothelial cells.

    Science.gov (United States)

    Bernardini, Chiara; Zannoni, Augusta; Turba, Maria Elena; Fantinati, Paolo; Tamanini, Carlo; Bacci, Maria Laura; Forni, Monica

    2005-01-01

    Lipopolysaccharide (LPS) is a highly proactive molecule that causes in vivo a systemic inflammatory response syndrome and activates in vitro the inflammatory pathway in different cellular types, including endothelial cells (EC). Because the proinflammatory status could lead to EC injury and apoptosis, the expression of proinflammatory genes must be finely regulated through the induction of protective genes. This study aimed at determining whether an LPS exposure is effective in inducing apoptosis in primary cultures of porcine aortic endothelial cells and in stimulating heat shock protein (Hsp)70 and Hsp32 production as well as vascular endothelial growth factor (VEGF) secretion. Cells between third and eighth passage were exposed to 10 microg/mL LPS for 1, 7, 15, and 24 hours (time-course experiments) or to 1, 10, and 100 microg/mL LPS for 7 and 15 hours (dose-response experiments). Apoptosis was not affected by 1 microg/mL LPS but significantly increased in a dose-dependent manner with the highest LPS doses. Furthermore, apoptosis rate increased only till 15 hours of LPS exposure. LPS stimulated VEGF secretion in a dose-dependent manner; its effect became significant after 7 hours and reached a plateau after 15 hours. Both Hsp70 and Hsp32 expressions were induced by LPS in a dose-dependent manner after 7 hours. Subsequent studies were addressed to evaluate the protective role of Hsp32, Hsp70, and VEGF. Hemin, an Hsp32 inducer (5, 20, 50 microM), and recombinant VEGF (100 and 200 ng/mL), were added to the culture 2 hours before LPS (10 microg/mL for 24 hours); to induce Hsp70 expression, cells were heat shocked (42 degrees C for 1 hour) 15 hours before LPS (10 microg/mL for 24 hours). Hemin exposure upregulated Hsp32 expression in a dose-dependent manner and protected cells against LPS-induced apoptosis. Heat shock (HS) stimulated Hsp70 expression but failed to reduce LPS-induced apoptosis; VEGF addition did not protect cells against LPS-induced apoptosis at any

  19. Direct Aortic CoreValve implantation via right anterior thoracotomy in a patient with patent bilateral mammary artery grafts and aortic arch chronic dissection

    Directory of Open Access Journals (Sweden)

    Giuseppe Bruschi

    2015-01-01

    Full Text Available Direct aortic trans-catheter aortic valve implantation is an alternative approach to treat high risk for surgery patients affected by severe aortic stenosis and concomitant peripheral vascular disease. We describe a case of direct aortic CoreValve implantation made via a right anterior thoracotomy in a 78-year-old male affected by severe aortic stenosis and severe peripheral vasculopathy, who previously underwent coronary artery bypass grafting, with patent bilateral mammary artery grafts and chronic aortic arch dissection.

  20. Exercise improves recognition memory and synaptic plasticity in the prefrontal cortex for rats modelling vascular dementia.

    Science.gov (United States)

    Dong, Juntao; Zhao, Jingpu; Lin, Yangyang; Liang, Huiying; He, Xiaokuo; Zheng, Xiuyuan; Sui, Minghong; Zhuang, Zhiqiang; Yan, Tiebin

    2018-01-01

    Functional electrical stimulation (FES) may induce involuntary exercise and make beneficial effects on vascular dementia (VD) by strengthening the BDNF-pCREB-mediated pathway and hippocampal plasticity. Whether FES improves recognition memory and synaptic plasticity in the prefrontal cortex (PFC) was investigated by establishing a VD model. The VD rats were administered with two weeks of voluntary exercise, forced exercise, or involuntary exercise induced with FES. Sham-operated and control groups were also included. The behavioral changes were assessed with the novel object recognition test and novel object location test. The expression levels of key proteins related to synaptic plasticity in the PFC were also detected. All types of exercise improved the rats' novel object recognition index, but only voluntary exercise and involuntary exercise induced with FES improved the novel object location index. Any sort of exercise enhanced the expression of key proteins in the PFC. Involuntary exercise induced with FES can improve recognition memory in VD better than forced exercise. The mechanism is associated with increased synaptic plasticity in the PFC. FES may be a useful alternative tool for cognitive rehabilitation.

  1. Identification of Primo-Vascular System in Abdominal Subcutaneous Tissue Layer of Rats

    Directory of Open Access Journals (Sweden)

    Chae Jeong Lim

    2015-01-01

    Full Text Available The primo-vascular system (PVS is a novel network identified in various animal tissues. However, the PVS in subcutaneous tissue has not been well identified. Here, we examined the putative PVS on the surface of abdominal subcutaneous tissue in rats. Hemacolor staining revealed dark blue threadlike structures consisting of nodes and vessels, which were frequently observed bundled with blood vessels. The structure was filled with various immune cells including mast cells and WBCs. In the structure, there were inner spaces (20–60 µm with low cellularity. Electron microscopy revealed a bundle structure and typical cytology common with the well-established organ surface PVS, which were different from those of the lymphatic vessel. Among several subcutaneous (sc PVS tissues identified on the rat abdominal space, the most outstanding was the scPVS aligned along the ventral midline. The distribution pattern of nodes and vessels in the scPVS closely resembled that of the conception vessel meridian and its acupoints. In conclusion, our results newly revealed that the PVS is present in the abdominal subcutaneous tissue layer and indicate that the scPVS tissues are closely correlated with acupuncture meridians. Our findings will help to characterize the PVS in the other superficial tissues and its physiological roles.

  2. Data on the mechanisms underlying succinate-induced aortic contraction

    Directory of Open Access Journals (Sweden)

    Natália A. Gonzaga

    2016-12-01

    Full Text Available We describe the mechanisms underlying the vascular contraction induced by succinate. The data presented here are related to the article entitled “Pharmacological characterization of the mechanisms underlying the vascular effects of succinate” (L.N. Leite, N.A. Gonzaga, J.A. Simplicio, G.T. Vale, J.M. Carballido, J.C. Alves-Filho, C.R. Tirapelli, 2016 [1]. Succinate acts as a signaling molecule by binding to a G-protein-coupled receptor termed GPR91, “Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors” (W. He, F.J. Miao, D.C. Lin, R.T. Schwandner, Z. Wang, J. Gao, J.L. Chen, H. Tian, L. Ling, 2004 [2]. Here we include data on the contractile effect of succinate in the aorta. Succinate contracted both endothelium-intact and endothelium-denuded aortic rings isolated from male Wistar rats or C57BL/6 mice. Succinate was less effective at inducing contraction in arteries isolated from GPR91-deficient mice, when compared to its vascular effect in aortas from wild type mice. SB203508 (p38MAK inhibitor, SP600125 (JNK inhibitor and Y27632 (Rho-kinase inhibitor reduced succinate-induced contraction in both endothelium-intact and endothelium-denuded rat aortic rings, while PD98059 (ERK1/2 inhibitor did not affect succinate-induced contraction. The contractile response induced by succinate on endothelium-intact and endothelium-denuded rat aortic rings was reduced by indomethacin (non-selective cyclooxygenase inhibitor, H7 (protein kinase C inhibitor, verapamil (Ca2+ channel blocker and tiron (superoxide anion scavenger.

  3. Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra Venom

    Directory of Open Access Journals (Sweden)

    Shin Yee Fung

    2012-01-01

    Full Text Available Mucuna pruriens Linn. (velvet bean has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value.

  4. Effect of magnesium on vascular tone and reactivity in pressurized mesenteric resistance arteries from spontaneously hypertensive rats.

    Science.gov (United States)

    Laurant, P; Touyz, R M; Schiffrin, E L

    1997-04-01

    This study examines the effects of magnesium on vascular tone and reactivity in mesenteric resistance arteries from 17-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Third-order branches of mesenteric arteries were mounted in a pressurized flow chamber and studied with constant flow and transmural pressure. The mesenteric arteries were perfused extra- and intra-luminally with physiological salt solution containing a normal (1.2 mmol/L), high (4.8 mmol/L), or low (0.15 mmol/L) magnesium concentration. Vascular reactivity to norepinephrine and vasopressin was examined when the agonists were applied extraluminally. High magnesium increased lumen diameter and decreased media thickness whereas low magnesium decreased lumen diameter and increased media thickness in mesenteric arteries from both SHR and WKY rats. The effects of magnesium on vascular tone were less in arteries from SHR compared with normotensive controls (p magnesium potentiated norepinephrine-induced vasoconstriction in SHR (p magnesium did not modify vasopressin-induced vasoconstriction in either SHR or WKY. High magnesium attenuated vasopressin- and norepinephrine-induced vasoconstriction in SHR (p magnesium attenuated only norepinephrine-induced vasoconstriction in WKY (p magnesium has differential modulatory effects on vascular tone and reactivity in mesenteric resistance arteries of SHR and WKY. Magnesium may play an important role in the modulation of peripheral resistance in hypertension.

  5. Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption of High Fructose Corn Syrup in Rats

    Directory of Open Access Journals (Sweden)

    Aburrahman Gun

    2016-01-01

    Full Text Available Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose-induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS. HFCS (6 weeks, 30% fed with drinking water caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks effectively restored this problem. Additionally, hypertension in HFCS-fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS-induced cardiovascular abnormalities could be prevented by CAPE treatment.

  6. Environmental Enrichment Improves Spatial Learning and Memory in Vascular Dementia Rats with Activation of Wnt/β-Catenin Signal Pathway.

    Science.gov (United States)

    Jin, Xinhao; Li, Tao; Zhang, Lina; Ma, Jingxi; Yu, Lehua; Li, Changqing; Niu, Lingchuan

    2017-01-13

    BACKGROUND Environmental enrichment (EE) has a beneficial effect on some neuropsychiatric disorders. In this study, we aimed to investigate whether environmental enrichment could improve the spatial learning and memory in rats with vascular dementia (VaD) and the mechanism underpinning it. MATERIAL AND METHODS Bilateral common carotid occlusion (2-vessel occlusion [2VO]) was used to develop the animal model of vascular dementia. Adult male Sprague-Dawley (SD) rats were used in the experiment and were randomly divided into 4 groups: sham group, 2VO group, sham+EE group, and 2VO+EE group (n=19/group). The 2VO group and 2VO+EE group underwent bilateral common carotid occlusion. Two different housing conditions were used in this experiment: standard environment (SE) and enriched environment (EE). Rats in the sham group and 2VO group were put into SE cages for 4 weeks, while rats in the sham+EE group and 2VO+EE group were put in EE cages for 4 weeks. The Morris water maze and Y-maze were used to assess spatial learning and memory. Apoptosis was detected by TUNEL. The damage of neurons in the hippocampus was assessed by Nissl staining. The level of wnt pathway proteins were detected by Western blot. RESULTS Compared with the 2VO group, the rats in the 2VO+EE group had better behavioral performance, fewer apoptotic neurons, and more surviving neurons. Western blot analysis showed that the levels of wnt pathway proteins were higher in 2VO+EE rats than in the 2VO group. CONCLUSIONS Environmental enrichment can improve the spatial learning and memory in rats with vascular dementia, and the mechanism may be related to activation of the wnt/β-catenin signal pathway.

  7. Notch signaling change in pulmonary vascular remodeling in rats with pulmonary hypertension and its implication for therapeutic intervention.

    Science.gov (United States)

    Qiao, Lina; Xie, Liang; Shi, Kun; Zhou, Tongfu; Hua, Yimin; Liu, Hanmin

    2012-01-01

    Pulmonary hypertension (PH) is a fatal disease that lacks an effective therapy. Notch signaling pathway plays a crucial role in the angiogenesis and vascular remodeling. However, its roles in vascular remodeling in PH have not been well studied. In the current study, using hypoxia-induced PH model in rat, we examined the expression of Notch and its downstream factors. Then, we used vessel strip culture system and γ-secretase inhibitor DAPT, a Notch signaling inhibitor to determine the effect of Notch signaling in vascular remodeling and its potential therapeutic value. Our results indicated that Notch 1-4 were detected in the lung tissue with variable levels in different cell types such as smooth muscle cells and endothelial cells of pulmonary artery, bronchia, and alveoli. In addition, following the PH induction, all of Notch1, Notch3, Notch4 receptor, and downstream factor, HERP1 in pulmonary arteries, mRNA expressions were increased with a peak at 1-2 weeks. Furthermore, the vessel wall thickness from rats with hypoxia treatment increased after cultured for 8 days, which could be decreased approximately 30% by DAPT, accompanied with significant increase of expression level of apoptotic factors (caspase-3 and Bax) and transformation of vascular smooth muscle cell (VSMC) phenotype from synthetic towards contractile. In conclusion, the current study suggested Notch pathway plays an important role in pulmonary vascular remodeling in PH and targeting Notch signaling pathway could be a valuable approach to design new therapy for PH.

  8. Notch signaling change in pulmonary vascular remodeling in rats with pulmonary hypertension and its implication for therapeutic intervention.

    Directory of Open Access Journals (Sweden)

    Lina Qiao

    Full Text Available Pulmonary hypertension (PH is a fatal disease that lacks an effective therapy. Notch signaling pathway plays a crucial role in the angiogenesis and vascular remodeling. However, its roles in vascular remodeling in PH have not been well studied. In the current study, using hypoxia-induced PH model in rat, we examined the expression of Notch and its downstream factors. Then, we used vessel strip culture system and γ-secretase inhibitor DAPT, a Notch signaling inhibitor to determine the effect of Notch signaling in vascular remodeling and its potential therapeutic value. Our results indicated that Notch 1-4 were detected in the lung tissue with variable levels in different cell types such as smooth muscle cells and endothelial cells of pulmonary artery, bronchia, and alveoli. In addition, following the PH induction, all of Notch1, Notch3, Notch4 receptor, and downstream factor, HERP1 in pulmonary arteries, mRNA expressions were increased with a peak at 1-2 weeks. Furthermore, the vessel wall thickness from rats with hypoxia treatment increased after cultured for 8 days, which could be decreased approximately 30% by DAPT, accompanied with significant increase of expression level of apoptotic factors (caspase-3 and Bax and transformation of vascular smooth muscle cell (VSMC phenotype from synthetic towards contractile. In conclusion, the current study suggested Notch pathway plays an important role in pulmonary vascular remodeling in PH and targeting Notch signaling pathway could be a valuable approach to design new therapy for PH.

  9. Prostacyclin production in rat aortic smooth muscle cells: role of protein kinase C, phospholipase D and cyclooxygenase-2 expression.

    Science.gov (United States)

    Frias, Miguel A; Dubouloz, Frédérique; Rebsamen, Michela C; Lang, Ursula

    2003-11-01

    The present study was designed to investigate the role of protein kinase C (PKC) and phospholipase D (PLD) in angiotensin II (AngII)- and phorbol ester (PMA)-induced cyclooxygenase-2 (COX-2) expression and prostacyclin (PGI(2)) production in rat aortic smooth muscle cells (VSMC). Prostacyclin production in cultured VSMC was determined by radioimmunoassay. PKC activity was examined by measuring the transfer of 32P from (gamma-32P)ATP to histone III-S. COX-2 expression was determined by Western blotting. To measure PLD activity, thin layer chromatography was used. AngII (50 nM) and PMA (100 nM) promoted the translocation of PKC activity from the cytosol to the membranes within 30 min, followed by a strong increase in PLD activity as well as COX-2 expression and PGI(2) production. After 48 h exposure to PMA, PKC was downregulated resulting in a complete suppression of its activity. PKC-downregulation and the PKC inhibitor CGP41251 abolished PMA- and AngII-induced PLD activation, suppressed the stimulatory effect of PMA on COX-2 expression and PGI(2) production and strongly inhibited that of AngII. Furthermore, AngII- and PMA-induced PGI(2) production depended on protein synthesis and COX-2 but not COX-1 activity. Inhibition of PLD-mediated phosphatidic acid (PA) formation by 1% 1-butanol abolished AngII-induced COX-2 expression and PGI(2) secretion, while dioctanoyl PA increased COX-2 expression and PGI(2) production in a time- and concentration-dependent manner. Our results indicate that in VSMC, AngII promotes PGI(2) production to a large extent through a rise in COX-2 expression which is mediated by PA generated from increased PKC-dependent PLD activity.

  10. Preliminary Studies of Acute Cadmium Administration Effects on the Calcium-Activated Potassium (SKCa and BKCa) Channels and Na+/K+-ATPase Activity in Isolated Aortic Rings of Rats.

    Science.gov (United States)

    Vassallo, Dalton V; Almenara, Camila C P; Broseghini-Filho, Gilson Brás; Teixeira, Ariane Calazans; da Silva, David Chaves F; Angeli, Jhuli K; Padilha, Alessandra S

    2017-09-13

    Cadmium is an environmental pollutant closely linked with cardiovascular diseases that seems to involve endothelium dysfunction and reduced nitric oxide (NO) bioavailability. Knowing that NO causes dilatation through the activation of potassium channels and Na+/K+-ATPase, we aimed to determine whether acute cadmium administration (10 μM) alters the participation of K+ channels, voltage-activated calcium channel, and Na+/K+-ATPase activity in vascular function of isolated aortic rings of rats. Cadmium did not modify the acetylcholine-induced relaxation. After L-NAME addition, the relaxation induced by acetylcholine was abolished in presence or absence of cadmium, suggesting that acutely, this metal did not change NO release. However, tetraethylammonium (a nonselective K+ channels blocker) reduced acetylcholine-induced relaxation but this effect was lower in the preparations with cadmium, suggesting a decrease of K+ channels function in acetylcholine response after cadmium incubation. Apamin (a selective blocker of small Ca2+-activated K+ channels-SKCa), iberiotoxin (a selective blocker of large-conductance Ca2+-activated K+ channels-BKCa), and verapamil (a blocker of calcium channel) reduced the endothelium-dependent relaxation only in the absence of cadmium. Finally, cadmium decreases Na+/K+-ATPase activity. Our results provide evidence that the cadmium acute incubation unaffected the calcium-activated potassium channels (SKCa and BKCa) and voltage-calcium channels on the acetylcholine vasodilatation. In addition, acute cadmium incubation seems to reduce the Na+/K+-ATPase activity.

  11. Rapamycin inhibits CaCl2-induced thoracic aortic aneurysm formation in rats through mTOR-mediated suppression of proinflammatory mediators.

    Science.gov (United States)

    Cao, Jiumei; Wu, Qihong; Geng, Liang; Chen, Xiaonan; Shen, Weifeng; Wu, Fang; Chen, Ying

    2017-08-01

    The aim of the present study was to investigate the effect of the mammalian target of rapamycin (mTOR) signaling pathway on thoracic aortic aneurysm (TAA) development. The study used a calcium chloride (CaCl2)‑induced rat TAA model to explore the potential role of mTOR signaling pathway in the disease development. Adult male Sprague‑Dawley rats underwent the periarterial exposure of thoracic aorta to either 0.5 M CaCl2 or normal saline, and a subgroup of CaCl2‑treated rats received rapamycin 1 day prior to surgery. Without pre‑administering rapamycin, significantly enhanced phosphorylation of mTOR and expression of proinflammatory cytokines [i.e., tumor necrosis factor α (TNF‑α), interleukin 6 (IL‑6), and interleukin (IL)‑1β] were observed in the CaCl2‑treated aortic segments 2 days post‑treatment compared with the NaCl‑treated segments. At 2 weeks post‑treatment, hematoxylin and eosin and Verhoeff‑Van Gieson staining revealed aneurysmal alteration and disappearance of normal wavy elastic structures in the aortic segments exposed to CaCl2. In contrast, the CaCl2‑induced TAA formation was inhibited by pre‑administering rapamycin to CaCl2‑treated rats, which demonstrated attenuated mTOR phosphorylation and downregulation of the proinflammatory mediators (i.e., TNF‑α, IL‑6, IL‑1β, matrix metallopeptidases 2 and 9) to the control level. Further in vitro cell culture experiments using aortic smooth muscle cell (SMC) suggested that the inhibition of the mTOR signaling pathway by rapamycin could promote the differentiation of SMCs, as reflected by the reduced expression of S100A4 and osteopontin. The present study indicated that the early enhanced mTOR signaling pathway in the TAA development and mTOR inhibitor rapamycin may inhibit CaCl2‑induced TAA formation.

  12. Natural reversal of pulmonary vascular remodeling and right ventricular remodeling in SU5416/hypoxia-treated Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Makhosazane Zungu-Edmondson

    Full Text Available Pulmonary arterial hypertension (PAH is a lethal disease and improved therapeutic strategies are needed. Increased pulmonary arterial pressure, due to vasoconstriction and vascular remodeling, causes right ventricle (RV failure and death in patients. The treatment of Sprague-Dawley rats with SU5416 injection and exposure to chronic hypoxia for three weeks followed by maintenance in normoxia promote progressive and severe PAH with pathologic features that resemble human PAH. At 5-17 weeks after the SU5416 injection, PAH is developed with pulmonary vascular remodeling as well as RV hypertrophy and fibrosis. The present study investigated subsequent events that occur in these PAH animals.At 35 weeks after the SU5416 injection, rats still maintained high RV pressure, but pulmonary vascular remodeling was significantly reduced. Metabolomics analysis revealed that lungs of normal rats and rats from the 35-week time point had different metabolomics profiles. Despite the maintenance of high RV pressure, fibrosis was resolved at 35-weeks. Masson's trichrome stain and Western blotting monitoring collagen 1 determined 12% fibrosis in the RV at 17-weeks, and this was decreased to 5% at 35-weeks. The level of myofibroblasts was elevated at 17-weeks and normalized at 35-weeks.These results suggest that biological systems possess natural ways to resolve pulmonary and RV remodeling. The resolution of RV fibrosis appears to involve the reduction of myofibroblast-dependent collagen synthesis. Understanding these endogenous mechanisms should help improve therapeutic strategies to treat PAH and RV failure.

  13. Exercise training protects against atherosclerotic risk factors through vascular NADPH oxidase, extracellular signal-regulated kinase 1/2 and stress-activated protein kinase/c-Jun N-terminal kinase downregulation in obese rats.

    Science.gov (United States)

    Touati, Sabeur; Montezano, Augusto C I; Meziri, Fayçal; Riva, Catherine; Touyz, Rhian M; Laurant, Pascal

    2015-02-01

    Exercise training reverses atherosclerotic risk factors associated with metabolic syndrome and obesity. The aim of the present study was to determine the molecular anti-inflammatory, anti-oxidative and anti-atherogenic effects in aorta from rats with high-fat diet-induced obesity. Male Sprague-Dawley rats were placed on a high-fat (HFD) or control (CD) diet for 12 weeks. The HFD rats were then divided into four groups: (i) sedentary HFD-fed rats (HFD-S); (ii) exercise trained (motor treadmill 5 days/week, 60 min/day, 12 weeks) HFD-fed rats (HFD-Ex); (iii) modified diet (HFD to CD) sedentary rats (HF/CD-S); and (iv) an exercise-trained modified diet group (HF/CD-Ex). Tissue levels of NADPH oxidase (activity and expression), NADPH oxidase (Nox) 1, Nox2, Nox4, p47(phox) , superoxide dismutase (SOD)-1, angiotensin AT1 and AT2 receptors, phosphorylated mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase (ERK) 1/2, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK)) and vascular cell adhesion molecule-1 (VCAM-1) were determined in the aorta. Plasma cytokines (tumour necrosis factor (TNF)-α and interleukin (IL)-6) levels were also measured. Obesity was accompanied by increases in NADPH oxidase activity, p47(phox) translocation, Nox4 and VCAM-1 protein expression, MAPK (ERK1/2, SAPK/JNK) phosphorylation and plasma TNF-α and IL-6 levels. Exercise training and switching from the HFD to CD reversed almost all these molecular changes. In addition, training increased aortic SOD-1 protein expression and decreased ERK1/2 phosphorylation. These findings suggest that protective effects of exercise training on atherosclerotic risk factors induced by obesity are associated with downregulation of NADPH oxidase, ERK1/2 and SAPK/JNK activity and increased SOD-1 expression. © 2014 Wiley Publishing Asia Pty Ltd.

  14. Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium.

    Science.gov (United States)

    Sobajima, Mitsuo; Nozawa, Takashi; Shida, Takuya; Ohori, Takashi; Suzuki, Takayuki; Matsuki, Akira; Inoue, Hiroshi

    2011-08-01

    Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.

  15. Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Kyotani, Yoji, E-mail: cd147@naramed-u.ac.jp [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Ota, Hiroyo [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Takasawa, Shin [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Kimura, Hiroshi [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Uno, Masayuki [Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Yoshizumi, Masanori [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan)

    2013-11-15

    Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin m

  16. Modulation of Hypoxia-Induced Pulmonary Vascular Leakage in Rats by Seabuckthorn (Hippophae rhamnoides L.

    Directory of Open Access Journals (Sweden)

    Jayamurthy Purushothaman

    2011-01-01

    Full Text Available Cerebral and pulmonary syndromes may develop in unacclimatized individuals shortly after ascent to high altitude resulting in high altitude illness, which may occur due to extravasation of fluid from intra to extravascular space in the brain, lungs and peripheral tissues. The objective of the present study was to evaluate the potential of seabuckthorn (SBT (Hippophae rhamnoides L. leaf extract (LE in curtailing hypoxia-induced transvascular permeability in the lungs by measuring lung water content, leakage of fluorescein dye into the lungs and further confirmation by quantitation of albumin and protein in the bronchoalveolar lavage fluid (BALF. Exposure of rats to hypoxia caused a significant increase in the transvascular leakage in the lungs. The SBT LE treated animals showed a significant decrease in hypoxia-induced vascular permeability evidenced by decreased water content and fluorescein leakage in the lungs and decreased albumin and protein content in the BALF. The SBT extract was also able to significantly attenuate hypoxia-induced increase in the levels of proinflammatory cytokines and decrease hypoxia-induced oxidative stress by stabilizing the levels of reduced glutathione and antioxidant enzymes. Pretreatment of the extract also resulted in a significant decrease in the circulatory catecholamines and significant increase in the vasorelaxation of the pulmonary arterial rings as compared with the controls. Further, the extract significantly attenuated hypoxia-induced increase in the VEGF levels in the plasma, BALF (ELISA and lungs (immunohistochemistry. These observations suggest that SBT LE is able to provide significant protection against hypoxia-induced pulmonary vascular leakage.

  17. Unique cell type-specific junctional complexes in vascular endothelium of human and rat liver sinusoids.

    Directory of Open Access Journals (Sweden)

    Cyrill Géraud

    Full Text Available Liver sinusoidal endothelium is strategically positioned to control access of fluids, macromolecules and cells to the liver parenchyma and to serve clearance functions upstream of the hepatocytes. While clearance of macromolecular debris from the peripheral blood is performed by liver sinusoidal endothelial cells (LSECs using a delicate endocytic receptor system featuring stabilin-1 and -2, the mannose receptor and CD32b, vascular permeability and cell trafficking are controlled by transcellular pores, i.e. the fenestrae, and by intercellular junctional complexes. In contrast to blood vascular and lymphatic endothelial cells in other organs, the junctional complexes of LSECs have not yet been consistently characterized in molecular terms. In a comprehensive analysis, we here show that LSECs express the typical proteins found in endothelial adherens junctions (AJ, i.e. VE-cadherin as well as α-, β-, p120-catenin and plakoglobin. Tight junction (TJ transmembrane proteins typical of endothelial cells, i.e. claudin-5 and occludin, were not expressed by rat LSECs while heterogenous immunreactivity for claudin-5 was detected in human LSECs. In contrast, junctional molecules preferentially associating with TJ such as JAM-A, B and C and zonula occludens proteins ZO-1 and ZO-2 were readily detected in LSECs. Remarkably, among the JAMs JAM-C was considerably over-expressed in LSECs as compared to lung microvascular endothelial cells. In conclusion, we show here that LSECs form a special kind of mixed-type intercellular junctions characterized by co-occurrence of endothelial AJ proteins, and of ZO-1 and -2, and JAMs. The distinct molecular architecture of the intercellular junctional complexes of LSECs corroborates previous ultrastructural findings and provides the molecular basis for further analyses of the endothelial barrier function of liver sinusoids under pathologic conditions ranging from hepatic inflammation to formation of liver metastasis.

  18. The future of aortic surgery in Europe

    DEFF Research Database (Denmark)

    Czerny, Martin; Bachet, Jean; Bavaria, Joseph

    2012-01-01

    the interested reader with an overview of how aortic surgery and (perhaps more accurately) aortic medicine has evolved in Europe, and its present standing; also to provide a glimpse into the future, trying to disseminate the thoughts of a group of people actively involved in the development of aortic medicine...... in Europe, namely the Vascular Domain of the European Association of Cardio-Thoracic Surgery (EACTS)....

  19. Repair of bone defects with prefabricated vascularized bone grafts and double-labeled bone marrow-derived mesenchymal stem cells in a rat model

    National Research Council Canada - National Science Library

    Jiang, Xiao-Rui; Yang, Hui-Ying; Zhang, Xin-Xin; Lin, Guo-Dong; Meng, Yong-Chun; Zhang, Pei-Xun; Jiang, Shan; Zhang, Chun-Lei; Huang, Fei; Xu, Lin

    2017-01-01

    ...) and osteoblasts (OBs). Rats were divided into five groups: Group A: in vitro prefabrication with EPCs-RFP + in vivo prefabrication with arteriovenous vascular bundle + secondary OBs-GFP implantation; Grou...

  20. A non-contrast self-navigated 3-dimensional MR technique for aortic root and vascular access route assessment in the context of transcatheter aortic valve replacement: proof of concept

    Energy Technology Data Exchange (ETDEWEB)

    Renker, Matthias [Medical University of South Carolina, Heart and Vascular Center, Charleston, SC (United States); University Hospital Giessen and Marburg, Department of Medicine I, Giessen (Germany); Varga-Szemes, Akos; Rier, Jeremy D.; Steinberg, Daniel H. [Medical University of South Carolina, Heart and Vascular Center, Charleston, SC (United States); Schoepf, U.J. [Medical University of South Carolina, Heart and Vascular Center, Charleston, SC (United States); Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Baumann, Stefan [Medical University of South Carolina, Heart and Vascular Center, Charleston, SC (United States); University of Heidelberg, 1st Department of Medicine, Faculty of Medicine Mannheim, University Medical Centre Mannheim (UMM), Mannheim (Germany); Piccini, Davide [Siemens Healthcare IM BM PI, Advanced Clinical Imaging Technology, Lausanne (Switzerland); University Hospital (CHUV) and University of Lausanne (UNIL), Department of Radiology, Lausanne (Switzerland); Zenge, Michael O.; Mueller, Edgar [Siemens AG Healthcare Sector, Erlangen (Germany); Rehwald, Wolfgang G. [Duke University Medical Center, Cardiovascular MR Center, Durham, NC (United States); Moellmann, Helge [Kerckhoff Heart and Thorax Center, Bad Nauheim (Germany); Hamm, Christian W. [University Hospital Giessen and Marburg, Department of Medicine I, Giessen (Germany); De Cecco, Carlo N. [Medical University of South Carolina, Heart and Vascular Center, Charleston, SC (United States); University of Rome ' ' Sapienza' ' -Polo Pontino, Department of Radiological Sciences, Oncology and Pathology, Latina (Italy)

    2016-04-15

    Due to the high prevalence of renal failure in transcatheter aortic valve replacement (TAVR) candidates, a non-contrast MR technique is desirable for pre-procedural planning. We sought to evaluate the feasibility of a novel, non-contrast, free-breathing, self-navigated three-dimensional (SN3D) MR sequence for imaging the aorta from its root to the iliofemoral run-off in comparison to non-contrast two-dimensional-balanced steady-state free-precession (2D-bSSFP) imaging. SN3D [field of view (FOV), 220-370 mm{sup 3}; slice thickness, 1.15 mm; repetition/echo time (TR/TE), 3.1/1.5 ms; and flip angle, 115 ] and 2D-bSSFP acquisitions (FOV, 340 mm; slice thickness, 6 mm; TR/TE, 2.3/1.1 ms; flip angle, 77 ) were performed in 10 healthy subjects (all male; mean age, 30.3 ± 4.3 yrs) using a 1.5-T MRI system. Aortic root measurements and qualitative image ratings (four-point Likert-scale) were compared. The mean effective aortic annulus diameter was similar for 2D-bSSFP and SN3D (26.7 ± 0.7 vs. 26.1 ± 0.9 mm, p = 0.23). The mean image quality of 2D-bSSFP (4; IQR 3-4) was rated slightly higher (p = 0.03) than SN3D (3; IQR 2-4). The mean total acquisition time for SN3D imaging was 12.8 ± 2.4 min. Our results suggest that a novel SN3D sequence allows rapid, free-breathing assessment of the aortic root and the aortoiliofemoral system without administration of contrast medium. (orig.)

  1. Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Tian; Wang, Chenlong; Chen, Xuewei; Duan, Chenfan; Zhang, Xiaoyan [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Chen, Honglei [Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yue, Jiang [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Li, Ying, E-mail: lyying0@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

    2015-07-15

    Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing the coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor

  2. Post-Weaning Protein Malnutrition Increases Blood Pressure and Induces Endothelial Dysfunctions in Rats

    Science.gov (United States)

    Siman, Fabiana D. M.; Silveira, Edna A.; Meira, Eduardo F.; da Costa, Carlos P.; Vassallo, Dalton V.; Padilha, Alessandra S.

    2012-01-01

    Malnutrition during critical periods in early life may increase the subsequent risk of hypertension and metabolic diseases in adulthood, but the underlying mechanisms are still unclear. We aimed to evaluate the effects of post-weaning protein malnutrition on blood pressure and vascular reactivity in aortic rings (conductance artery) and isolated-perfused tail arteries (resistance artery) from control (fed with Labina®) and post-weaning protein malnutrition rats (offspring that received a diet with low protein content for three months). Systolic and diastolic blood pressure and heart rate increased in the post-weaning protein malnutrition rats. In the aortic rings, reactivity to phenylephrine (10−10–3.10−4 M) was similar in both groups. Endothelium removal or L-NAME (10−4 M) incubation increased the response to phenylephrine, but the L-NAME effect was greater in the aortic rings from the post-weaning protein malnutrition rats. The protein expression of the endothelial nitric oxide isoform increased in the aortic rings from the post-weaning protein malnutrition rats. Incubation with apocynin (0.3 mM) reduced the response to phenylephrine in both groups, but this effect was higher in the post-weaning protein malnutrition rats, suggesting an increase of superoxide anion release. In the tail artery of the post-weaning protein malnutrition rats, the vascular reactivity to phenylephrine (0.001–300 µg) and the relaxation to acetylcholine (10−10–10−3 M) were increased. Post-weaning protein malnutrition increases blood pressure and induces vascular dysfunction. Although the vascular reactivity in the aortic rings did not change, an increase in superoxide anion and nitric oxide was observed in the post-weaning protein malnutrition rats. However, in the resistance arteries, the increased vascular reactivity may be a potential mechanism underlying the increased blood pressure observed in this model. PMID:22529948

  3. Graft infections after surgical aortic reconstructions

    NARCIS (Netherlands)

    Berger, P.

    2015-01-01

    Prosthetic vascular grafts are frequently used to reconstruct (part) of the aorta. Every surgical procedure caries a certain risk for infection and when a prosthetic aortic graft is implanted, this may lead to an aortic graft infection (AGI). Endovascular techniques have gradually replaced open

  4. Genetic and Epigenetic Regulation of Aortic Aneurysms

    Directory of Open Access Journals (Sweden)

    Ha Won Kim

    2017-01-01

    Full Text Available Aneurysms are characterized by structural deterioration of the vascular wall leading to progressive dilatation and, potentially, rupture of the aorta. While aortic aneurysms often remain clinically silent, the morbidity and mortality associated with aneurysm expansion and rupture are considerable. Over 13,000 deaths annually in the United States are attributable to aortic aneurysm rupture with less than 1 in 3 persons with aortic aneurysm rupture surviving to surgical intervention. Environmental and epidemiologic risk factors including smoking, male gender, hypertension, older age, dyslipidemia, atherosclerosis, and family history are highly associated with abdominal aortic aneurysms, while heritable genetic mutations are commonly associated with aneurysms of the thoracic aorta. Similar to other forms of cardiovascular disease, family history, genetic variation, and heritable mutations modify the risk of aortic aneurysm formation and provide mechanistic insight into the pathogenesis of human aortic aneurysms. This review will examine the relationship between heritable genetic and epigenetic influences on thoracic and abdominal aortic aneurysm formation and rupture.

  5. Genetic and Epigenetic Regulation of Aortic Aneurysms.

    Science.gov (United States)

    Kim, Ha Won; Stansfield, Brian K

    2017-01-01

    Aneurysms are characterized by structural deterioration of the vascular wall leading to progressive dilatation and, potentially, rupture of the aorta. While aortic aneurysms often remain clinically silent, the morbidity and mortality associated with aneurysm expansion and rupture are considerable. Over 13,000 deaths annually in the United States are attributable to aortic aneurysm rupture with less than 1 in 3 persons with aortic aneurysm rupture surviving to surgical intervention. Environmental and epidemiologic risk factors including smoking, male gender, hypertension, older age, dyslipidemia, atherosclerosis, and family history are highly associated with abdominal aortic aneurysms, while heritable genetic mutations are commonly associated with aneurysms of the thoracic aorta. Similar to other forms of cardiovascular disease, family history, genetic variation, and heritable mutations modify the risk of aortic aneurysm formation and provide mechanistic insight into the pathogenesis of human aortic aneurysms. This review will examine the relationship between heritable genetic and epigenetic influences on thoracic and abdominal aortic aneurysm formation and rupture.

  6. Evaluation of blood pressure and aortic elasticity of offspring of diabetic Wistar rats who have consumed flaxseed oil during pregnancy and lactation.

    Science.gov (United States)

    Vicente, Gabriela Câmara; Correia-Santos, André Manoel; Chagas, Maurício Alves; Boaventura, Gilson Teles

    2017-04-01

    This study aimed to investigate whether maternal use of flaxseed oil has effects on blood pressure and aorta elastic fibre in female offspring of diabetic mothers. Diabetes was induced into the rats (n = 18) by a high-fat diet and streptozotocin. After diabetes confirmation, rats were mated, and after pregnancy was confirmed, they were allocated into three groups: control group (CG); high-fat group (HFG); and flaxseed oil group (FOG). At weaning, female offspring (n = 6/group) received standard chow diet and were euthanized at 100 days of life. The following blood pressure and the percentage of the aortic elastic fibre were analysed. HFG showed higher blood pressure, and the use of flaxseed oil avoided this condition in FOG (p < 0.001) and increased the percentage of the aortic elastic fibre (p < 0.022). Flaxseed oil reduced the damage caused by maternal hyperglycaemia, promoting normal blood pressure and elasticity of the aorta in female offspring.

  7. Inhibition of Prostaglandin Transporter (PGT Promotes Perfusion and Vascularization and Accelerates Wound Healing in Non-Diabetic and Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Zhongbo Liu

    Full Text Available Peripheral ischemia, resulting from diminished arterial flow and defective local vascularization, is one of the main causes of impaired wound healing in diabetes. Vasodilatory prostaglandins (PGs, including PGE2 and PGI2, regulate blood flow in peripheral tissues. PGs also stimulate angiogenesis by inducing vascular endothelial growth factor. However, PG levels are reduced in diabetes mainly due to enhanced degradation. We hypothesized that inhibition of the prostaglandin transporter (PGT (SLCO2A1, which mediates the degradation of PGs, would increase blood flow and stimulate vascularization, thereby mitigating peripheral ischemia and accelerating wound healing in diabetes. Here we report that inhibiting PGT with intravenously injected PGT inhibitor, T26A, increased blood flow in ischemic hind limbs created in non-diabetic rats and streptozotocin induced diabetic rats. Systemic, or combined with topical, T26A accelerated closure of cutaneous wounds. Immunohistochemical examination revealed that inhibition of PGT enhanced vascularization (marked by larger numbers of vessels formed by CD34+ cells, and accelerated re-epithelialization of cutaneous wounds. In cultured primary human bone marrow CD34+ cells and human epidermal keratinocytes (HEKs either inhibiting or silencing PGT increased migration in both cell lines. Thus PGT directly regulates mobilization of endothelial progenitor cells (EPCs and HEKs, which could contribute to PGT-mediated vascularization and re-epithelialization. At the molecular level, systemic inhibition of PGT raised circulating PGE2. Taken together, our data demonstrate that PGT modulates arterial blood flow, mobilization of EPCs and HEKs, and vascularization and epithelialization in wound healing by regulating vasodilatory and pro-angiogenic PGs.

  8. Finasteride reduces microvessel density and expression of vascular endothelial growth factor in renal tissue of diabetic rats.

    Science.gov (United States)

    Tian, He-lin; Zhao, Chao-xian; Wu, Hai-ying; Xu, Zhong-xin; Wei, Li-shun; Zhao, Ru-tong; Jin, Dong-ling

    2015-06-01

    Vascular endothelial growth factor (VEGF) plays a critical role in the pathogenesis of diabetic microvascular complications. Finasteride has been confirmed to decrease VEGF expression in prostate and prostatic suburethral tissue resulting in limiting hematuria from human benign prostatic hyperplasia. The purpose of this study was to evaluate the effects of finasteride on microvessel density (MVD), VEGF protein and mRNA expressions in the renal tissue of diabetic rats. Diabetic rats induced by streptozotocin were intragastrically given finasteride at 30 mg/kg body weight once a day for 4 weeks. Histomorphologic changes in kidney were observed under light microscope. Immunohistochemistry for CD34 and VEGF on kidney sections was performed to assess MVD and VEGF protein expression in glomeruli of rats, respectively. The VEGF mRNA expression in the renal tissue was examined using reverse transcription polymerase chain reaction analysis. The glomerular tuft area, glomerular volume, MVD, VEGF protein expression in glomeruli and VEGF mRNA expression in the renal cortex tissue were significantly increased in diabetic rats and finasteride-treated rats when compared with controls (P finasteride-treated rats were significantly decreased (P Finasteride reduces the VEGF expression and decreases the MVD in the renal tissue of diabetic rats, suggesting the therapeutic potential of finasteride on diabetic microvascular complications.

  9. PVP formulated Fullerene (C60) increases Rho-kinase dependent Vascular Tissue Contractility in Pregnant Sprague Dawley Rats

    Science.gov (United States)

    Vidanapathirana, Achini K.; Thompson, Leslie C.; Mann, Erin. E.; Odom, Jillian T.; Holland, Nathan A.; Sumner, Susan J.; Han, Li; Lewin, Anita H.; Fennell, Timothy R.; Brown, Jared M.; Wingard, Christopher J.

    2014-01-01

    Pregnancy is a unique physiological state, in which C60 fullerene is reported to be distributed in both maternal and fetal tissues. Tissue distribution of C60 differs between pregnant and non-pregnant states, presumably due to functional changes in vasculature during pregnancy. We hypothesized that, polyvinylpyrorrolidone (PVP) formulated C60 (C60/PVP) increases vascular tissue contractility during pregnancy by increasing Rho-kinase activity. C60/PVP was administered intravenously to pregnant and non-pregnant female Sprague Dawley rats. Vascular responses were assessed using wire myography 24 hours post-exposure. Increased stress generation was observed in uterine artery, thoracic aorta and umbilical vein. Rho-Rho-kinase mediated force maintenance was increased in arterial segments from C60/PVP exposed pregnant rats when compared to PVP exposed rats. Our findings suggest that intravenous exposure to C60/PVP during pregnancy increases vascular tissue contractility of the uterine artery through elements of Rho-Rho-kinase signaling during late stages of pregnancy. PMID:25088243

  10. Effects of prolonged ingestion of epigallocatechin gallate on diabetes type 1-induced vascular modifications in the erectile tissue of rats.

    Science.gov (United States)

    Lombo, C; Morgado, C; Tavares, I; Neves, D

    2016-07-01

    Diabetes Mellitus type 1 is a metabolic disease that predisposes to erectile dysfunction, partly owing to structural and molecular changes in the corpus cavernosum (CC) vessels. The aim of this study was to determine the effects of early treatment with the antioxidant epigallocatechin gallate (EGCG) in cavernous diabetes-induced vascular modifications. Diabetes was induced in two groups of young Wistar rats; one group was treated with EGCG for 10 weeks. A reduction in smooth muscle content was observed in the CC of diabetic rats, which was significantly attenuated with EGCG consumption. No differences were observed among groups, neither in the expression of VEGF assayed by western blotting nor in the immunofluorescent labeling of vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2). VEGFR2 was restricted to the endothelium, whereas VEGF and VEGFR1 co-localized in the smooth muscle layer. With regard to the Angiopoietin/Tie-2 system, no quantitative differences in Angiopoietin 1 were observed among the experimental groups. Ang1 localization was restricted to the smooth muscle layer, and receptor Tie2 and Angiopoietin 2 were both expressed in the endothelium. In brief, our results suggest that EGCG consumption prevented diabetes-induced loss of cavernous smooth muscle but does not affect vascular growth factor expression in young rats.

  11. Neuroprotective and memory enhancing effects of auraptene in a rat model of vascular dementia: Experimental study and histopathological evaluation.

    Science.gov (United States)

    Ghanbarabadi, Mustafa; Iranshahi, Mehrdad; Amoueian, Sakineh; Mehri, Soghra; Motamedshariaty, Vahideh Sadat; Mohajeri, Seyed Ahmad

    2016-06-03

    Vascular dementia and Alzheimer disease are most common type of dementia. These diseases have been associated with cognitive decline and affected personal behavioral activities. Moreover, the pattern of cerebral blood flow in mild cognitive disorder has appeared as a predictive indication for the development into Alzheimer's disease. Permanent, bilateral occlusion of the common carotid arteries (2VO) is a standard animal model to study vascular dementia and chronic cerebral hypoperfusion. In present study neuroprotective and memory enhancing effects of auraptene (AUR), a citrus coumarin, were studied in 2VO rats. Different doses (25, 8 & 4mg/kg) of AUR were administered orally. The spatial memory performance was tested with Morris water maze after 2VO induction. Biochemical experiments and histopathological evaluations were also applied to investigate the neuroprotective effect of AUR in brain tissue. In comparison with 2VO group, AUR could significantly decrease the scape latency time in treated rats. Also AUR increased the percentage of time spent and traveled pathway in target quadrant on final trial test day. All behavioral results were confirmed by biochemical and histopathological data. Biochemical data indicated that AUR could decrease malondialdehyde (MDA), as lipid peroxidation indicator, and increase glutathione (GSH) content in cortex and hippocampus tissues. Histopathological data showed that AUR could protect cerebrocortical and hippocampus neurons against ischemia. This study demonstrated the memory enhancing effect and neuroprotective activity of AUR after induction of brain ischemia in a rat model of vascular dementia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Isoproterenol attenuates high vascular pressure-induced permeability increases in isolated rat lungs.

    Science.gov (United States)

    Parker, J C; Ivey, C L

    1997-12-01

    To separate the contributions of cellular and basement membrane components of the alveolar capillary barrier to the increased microvascular permeability induced by high pulmonary venous pressures (Ppv), we subjected isolated rat lungs to increases in Ppv, which increased capillary filtration coefficient (Kfc) without significant hemorrhage (31 cmH2O) and with obvious extravasation of red blood cells (43 cmH2O). Isoproterenol (20 microM) was infused in one group (Iso) to identify a reversible cellular component of injury, and residual blood volumes were measured to assess extravasation of red blood cells through ruptured basement membranes. In untreated lungs (High Ppv group), Kfc increased 6.2 +/- 1.3 and 38.3 +/- 15.2 times baseline during the 31 and 43 cmH2O Ppv states. In Iso lungs, Kfc was 36.2% (P Kfc increases at moderate Ppv, possibly because of an endothelial effect, but it did not affect red cell extravasation at higher vascular pressures.

  13. Ceramide 1-phosphate induces neointimal formation via cell proliferation and cell cycle progression upstream of ERK1/2 in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tack-Joong, E-mail: ktj@yonsei.ac.kr [Division of Biological Science and Technology, College of Science and Technology, Yonsei University, Wonju 220-710 (Korea, Republic of); Kang, Yeo-Jin [Division of Biological Science and Technology, College of Science and Technology, Yonsei University, Wonju 220-710 (Korea, Republic of); Lim, Yong [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Lee, Hyoung-Woo [Division of Biological Science and Technology, College of Science and Technology, Yonsei University, Wonju 220-710 (Korea, Republic of); College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Bae, Kiho [Division of Biological Science and Technology, College of Science and Technology, Yonsei University, Wonju 220-710 (Korea, Republic of); Lee, Youn-Sun; Yoo, Jae-Myung; Yoo, Hwan-Soo; Yun, Yeo-Pyo [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of)

    2011-08-15

    Ceramide 1-phosphate (C1P) is a novel bioactive sphingolipid formed by ceramide kinase (CERK)-catalyzed phosphorylation of ceramide. It has been implicated in the regulation of such vital pathophysiological functions as phagocytosis and inflammation, but there have been no reports ascribing a biological function to CERK in vascular disorders. Here the potential role of CERK/C1P in neointimal formation was investigated using rat aortic vascular smooth muscle cells (VSMCs) in primary culture and a rat carotid injury model. Exogenous C8-C1P stimulated cell proliferation, DNA synthesis, and cell cycle progression of rat aortic VSMCs in primary culture. In addition, wild-type CERK-transfected rat aortic VSMCs induced a marked increase in rat aortic VSMC proliferation and [{sup 3}H]-thymidine incorporation when compared to empty vector transfectant. C8-C1P markedly activated extracellular signal-regulated kinase 1 and 2 (ERK1/2) within 5 min, and the activation could be prevented by U0126, a MEK inhibitor. Also, K1, a CERK inhibitor, decreased the ERK1/2 phosphorylation and cell proliferation on platelet-derived growth factor (PDGF)-stimulated rat aortic VSMCs. CERK expression and C1P levels were found to be potently increased during neointimal formation using a rat carotid injury model. However, ceramide levels decreased during the neointimal formation process. These findings suggest that C1P can induce neointimal formation via cell proliferation through the regulation of the ERK1/2 protein in rat aortic VSMCs and that CERK/C1P may regulate VSMC proliferation as an important pathogenic marker in the development of cardiovascular disorders.

  14. Impaired vascular responses to relaxin in diet-induced overweight female rats.

    NARCIS (Netherlands)

    Drongelen, J. van; Koppen, A. van; Pertijs, J.C.L.M.; Gooi, J.H.; Parry, L.J.; Sweep, F.C.; Lotgering, F.K.; Smits, P.; Spaanderman, M.E.A.

    2012-01-01

    Relaxin mediates renal and mesenteric vascular adaptations to pregnancy by increasing endothelium-dependent vasodilation and compliance and decreasing myogenic reactivity. Diet-induced overweight and obesity are associated with impaired endothelial dysfunction and vascular remodeling leading to a

  15. Amlodipine enhances amelioration of vascular insulin resistance, oxidative stress, and metabolic disorders by candesartan in metabolic syndrome rats.

    Science.gov (United States)

    Sueta, Daisuke; Nakamura, Taishi; Dong, Yi-Fei; Kataoka, Keiichiro; Koibuchi, Nobutaka; Yamamoto, Eiichiro; Toyama, Kensuke; Yasuda, Osamu; Ogawa, Hisao; Kim-Mitsuyama, Shokei

    2012-06-01

    The pharmacological advantage of combination of an angiotensin receptor blocker (ARB) and a calcium-channel blocker (CCB) is not fully defined. This study was undertaken to elucidate the potential benefit of their combination in metabolic syndrome. SHR/NDmcr-cp (SHRcp), a rat model of human metabolic syndrome, were divided into four groups, and were administered (i) vehicle, (ii) candesartan (an ARB) 0.3 mg/kg/day, (iii) amlodipine (a CCB) 3 mg/kg/day, and (iv) candesartan 0.3 mg/kg/day plus amlodipine 3 mg/kg/day, for 4 weeks. Candesartan, amlodipine, or their combination significantly ameliorated the impairment of vascular endothelium-dependent relaxation with acetylcholine in SHRcp. However, the impairment of insulin-induced vasodilation in SHRcp was partially improved by candesartan alone, but not by amlodipine alone. Interestingly, amlodipine added to candesartan synergistically enhanced the improvement of impaired insulin-induced vasodilation by candesartan, indicating the synergistic improvement of vascular insulin resistance by the combination of these drugs. Candesartan alone, but not amlodipine alone, significantly attenuated vascular superoxide and NADPH oxidase subunit p22phox in SHRcp. Amlodipine added to candesartan synergistically enhanced the reduction of vascular p22phox levels and superoxide by candesartan in SHRcp, suggesting the association of vascular insulin resistance with oxidative stress. Furthermore, the combination of candesartan with amlodipine synergistically decreased the increase in visceral adipocyte size, serum free-fatty acid, and tumor necrosis factor-α in SHRcp. ARB and CCB combination synergistically ameliorated vascular insulin resistance in metabolic syndrome, being associated with the synergistic attenuation of vascular oxidative stress and metabolic disorders.

  16. Super, Red Palm and Palm Oleins Improve the Blood Pressure, Heart Size, Aortic Media Thickness and Lipid Profile in Spontaneously Hypertensive Rats

    Science.gov (United States)

    Boon, Chee-Meng; Ng, Mei-Han; Choo, Yuen-May; Mok, Shiueh-Lian

    2013-01-01

    Background Oleic acid has been shown to lower high blood pressure and provide cardiovascular protection. Curiosity arises as to whether super olein (SO), red palm olein (RPO) and palm olein (PO), which have high oleic acid content, are able to prevent the development of hypertension. Methodology/Principal Findings Four-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were fed 15% SO, RPO or PO supplemented diet for 15 weeks. After 15 weeks of treatment, the systolic blood pressure (SBP) of SHR treated with SO, RPO and PO were 158.4±5.0 mmHg (pOil Red O enface staining of thoracic-abdominal aorta did not show any lipid deposition in all treated rats. The SO and RPO significantly raised serum alkaline phosphatase levels in the SHR while body weight and renal biochemical indices were unaltered in both strains. Serum lipid profiles of treated SHR and WKY rats were unchanged, with the exception of a significant reduction in LDL-C level and total cholesterol/HDL ratio (atherogenic index) in SO and RPO treated SHR compared with untreated SHR. Conclusion The SO, RPO and PO attenuate the rise in blood pressure in SHR, accompanied by bradycardia and heart size reduction with SO and PO, and aortic media thickness reduction with SO, RPO and PO. The SO and RPO are antiatherogenic in nature by improving blood lipid profiles in SHR. PMID:23409085

  17. Effects of intracerebroventricular injections of 5-HT on systemic vascular resistances of conscious rats.

    Science.gov (United States)

    Davisson, Robin L; Bates, James N; Johnson, Alan Kim; Lewis, Stephen J

    2014-09-01

    The aims of this study were to determine (i) the effects of intracerebroventricular (i.c.v.) injections of 5-hydroxytryptamine (5-HT, 10μg) on mean arterial blood pressure (MAP), heart rate (HR) and mesenteric (MR), renal (RR) and hindquarter (HQR) vascular resistances of conscious rats, (ii) the central 5-HT receptor subtype which mediates these effects, and (iii) the role of nitric oxide (NO) in the expression of these responses. The i.c.v. injection of 5-HT had minor effects on MAP but produced a decrease in HR (-18±4%), which lasted for 20min. The i.c.v. injection of 5-HT elicited marked increases in MR (+50±7%) and reductions in HQR (-31±3%). These responses occurred promptly and lasted for 25-35min. 5-HT also produced a transient decrease in RR (-26±8% at 10min). All of these responses were prevented by the prior i.c.v. injection of the 5-HT1/5-HT2-receptor antagonist, methysergide (10μg). The intravenous injection of the NO synthesis inhibitor, L-NAME (25μmol/kg), produced a sustained pressor response, bradycardia and increases in MR, RR and HQR. Subsequent i.c.v. injection of 5-HT produced a minor pressor response (+7±2%), bradycardia (-18±3%), an increase in MR (+52±8%) but no decreases in RR or HQR. This study demonstrates that i.c.v. 5-HT differentially affects peripheral vascular resistances by activation of central 5-HT1/5-HT2-receptors. It appears that L-NAME did not interfere with the central actions of 5-HT as it did not prevent the 5-HT-induced bradycardia or mesenteric vasoconstriction. Since the 5-HT-induced falls in RR and HQR were abolished by L-NAME, it is possible that these responses are mediated by an active neurogenic process involving the release of NO within the vasculature. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Erythroxylum pungens elicits vasorelaxation by reducing intracellular calcium concentration in vascular smooth muscle cells of rats

    Directory of Open Access Journals (Sweden)

    Aurylene C. Oliveira

    2012-01-01

    Full Text Available The cardiovascular effects elicited by the ethanolic extract obtained from the roots of Erythroxylum pungens O.E. Schulz, Erythroxylaceae (EEEP and the vasorelaxant effect induced by its main tropane alkaloid (pungencine were investigated. In normotensive rats, administration of EEEP (1, 10, 30 and 60 mg/kg i.v., randomly produced dose-dependent hypotension (-2±1, -7±0.5 -17.6±1, -24±1 Δ mmHg, n=5 followed by tachycardia (3±0.5, 7±2, 7.1±1, 10±5 Δ bpm, n=5. In intact phenylephrine (Phe, 10 µM-pre-contracted rings, EEEP (0.01-500 µg/mL induced concentration-dependent vasorelaxation (EC50 13.7±5.5 µg/mL, Maximal Response= 92±2.6%, and this effect was unchanged after the removal of the vascular endothelium (EC50 27.2±4.7 µg/ml, Maximal Response= 88.3±3.3 %. In KCl (80 mM-pre-contracted-endothelium-denuded rings, EEEP elicited concentration-dependent relaxation (EC50= 128.2±11.2 µg/mL, Maximal Response 76.8±3.4%. Vasorelaxation has also been achieved with tonic contractions evoked by the L-type Ca2+ channel agonist Bay K 8644 (EC50 80.2±9.1 µg/mL, Maximal Response 86.3±8.3%. In addition, in a depolarizing medium, EEEP inhibited CaCl2 (30-500 µg/mL induced contractions and caused a concentration-dependent rightward shift of the relaxation curves. Lastly, the tropane alkaloid pungencine caused vasorelaxation in mesenteric arteries resembling to the EEEP responses. These results suggests that EEEP induces hypotension and vasorelaxation, at least in part, due to the reduction in [Ca2+]i in vascular smooth muscle cells.

  19. Protective vascular effects of quercitrin in acute TNBS-colitis in rats: the role of nitric oxide.

    Science.gov (United States)

    Romero, Miguel; Vera, Beatriz; Galisteo, Milagros; Toral, Marta; Gálvez, Julio; Perez-Vizcaino, Francisco; Duarte, Juan

    2017-08-01

    Quercitrin (quercetin 3-rhamnoside) is a bioflavonoid with anti-inflammatory activity in experimental colitis. Several studies have suggested that vascular injury might be a primary process in Crohn's disease, but there is no information about the function of the mesenteric bed in the experimental models of colitis. The aims of this study were to analyse whether the reactivity to vasoconstrictor agents is altered in the mesenteric vascular bed from animals with colitis induced by administration of trinitrobenzenesulfonic acid (TNBS) in the early stages of this pathology, and to determine the effects of quercitrin on such vascular alterations. Contraction of mesenteric beds produced by vasoconstrictor agents such as noradrenaline and KCl is reduced in rats in the early stages of experimental TNBS-induced colitis. This alteration was partially reverted by non-selective nitric oxide synthase (NOS) inhibition with N-nitro-l-arginine methylester, and enhanced by non-selective cyclooxygenase (COX) inhibition with indomethacin. However, the endothelium-dependent relaxant responses to acetylcholine were not significantly altered. iNOS, COX-2, NOX-1, tumor necrosis factor α (TNFα) and interleukin 1β (IL1β) expressions were higher in the mesenteric arteries from TNBS-treated rats, without changes in both eNOS expression and eNOS-Ser1177 phosphorylation. The in vivo pre-treatment with 5 mg kg-1 of the flavonoid quercitrin reverts both the early hyporesponse of mesenteric arteries to noradrenaline and the up-regulation of iNOS, COX2, NOX1, TNFα and IL1β in colitic rats. In conclusion, quercitrin improves the impaired mesenteric vascular reactivity in the acute phase of this colitis model, at least in part by reducing NO overproduction from iNOS.

  20. Implication of Free Fatty Acids in Thrombin Generation and Fibrinolysis in Vascular Inflammation in Zucker Rats and Evolution with Aging

    Directory of Open Access Journals (Sweden)

    Jérémy Lagrange

    2017-11-01

    Full Text Available Background: The metabolic syndrome (MetS and aging are associated with modifications in blood coagulation factors, vascular inflammation, and increased risk of thrombosis.Objectives: Our aim was to determine concomitant changes in thrombin generation in the blood compartment and at the surface of vascular smooth muscle cells (VSMCs and its interplay with adipokines, free fatty acids (FFA, and metalloproteinases (MMPs in obese Zucker rats that share features of the human MetS.Methods: Obese and age-matched lean Zucker rats were compared at 25 and 80 weeks of age. Thrombin generation was assessed by calibrated automated thrombography (CAT.Results: Endogenous thrombin potential (ETP was increased in obese rats independent of platelets and age. Clot half-lysis time was delayed with obesity and age. Interleukin (IL-1β and IL-13 were increased with obesity and age respectively. Addition of exogenous fibrinogen, leptin, linoleic, or palmitic acid increased thrombin generation in plasma whereas adiponectin had an opposite effect. ETP was increased at the surface of VSMCs from obese rats and addition of exogenous palmitic acid further enhanced ETP values. Gelatinase activity was increased in aorta at both ages in obese rats and MMP-2 activity was increased in VSMCs from obese rats.Conclusions: Our study demonstrated in MetS an early prothrombotic phenotype of the blood compartment reinforced by procoagulant properties of dedifferentiated and inflammatory VSMCs. Mechanisms involved (1 increased fibrinogen and impaired fibrinolysis and (2 increased saturated fatty acids responsible for additive procoagulant effects. Whether specifically targeting this hypercoagulability using direct thrombin inhibitors would improve outcome in MetS is worth investigating.

  1. Vascular surgical society of great britain and ireland: immunoglobulin A antibodies against chlamydia pneumoniae are associated with expansion of small abdominal aortic aneurysms and declining ankle blood pressure

    DEFF Research Database (Denmark)

    Lindholt, Jes S.; Vammen; Henneberg

    1999-01-01

    BACKGROUND: The potential correlation between chronic infection with Chlamydia pneumoniae and the progression of small abdominal aortic aneurysms (AAAs) and lower limb atherosclerosis was studied. METHODS: Mass screening for AAA was carried out in outdoor clinics at all hospitals in the county....... CONCLUSION: A high proportion of men with a small AAA have signs of chronic C. pneumoniae infection. The progression of AAAs and lower limb atherosclerosis seems to be correlated to chronic infection with C. pneumoniae....

  2. Long-term effects of maternal diabetes on vascular reactivity and renal function in rat male offspring.

    Science.gov (United States)

    Rocha, Silvia O; Gomes, Guiomar N; Forti, André Luis L; do Carmo Pinho Franco, Maria; Fortes, Zuleica B; de Fátima Cavanal, Maria; Gil, Frida Zaladek

    2005-12-01

    Fetal growth impairment can occur in pregnancy complicated by diabetes. Although several studies have focused the effects of nutritional status on intrauterine development, the long-term impact of maternal diabetes on vascular and renal function in the offspring is poorly investigated. In the present study, blood pressure profiles and renal function parameters were investigated in the offspring of diabetic rats (DO). Female rats were made diabetic throughout gestation with a single dose of streptozotocyn (STZ) 10 d before mating. After weaning, the offspring had free access to food and water. Arterial pressure was evaluated every 15 d. Functional and morphometric kidney studies were performed in newborn, 3, 6 and 12-mo-old male rats in DO and in controls, C. Although maternal diabetes did not affect nephron number in the young adult rat, glomerular hypertrophy developed from 3 mo on. Glomerular Filtration Rate and Renal Plasma Flow were observed to be significantly decreased in DO when compared with C, from 3 mo on. In DO, hypertension was observed from 8 wk on and persisted elevated throughout the experimental period (12 mo). Vascular reactivity, evaluated in mesenteric arterial bed showed a decreased endothelium-dependent vasodilatation in 12-mo-old DO animals, while preserved response to sodium nitroprusside was demonstrated. Our data show that exposure to intrauterine diabetes induced by STZ does not affect nephron number in the young offspring but can cause permanent changes in Nitric Oxide (NO)-related vascular response, which, in turn may accelerate the natural age-related nephron loss.

  3. Aliskiren-binding increases the half life of renin and prorenin in rat aortic vascular smooth muscle cells

    NARCIS (Netherlands)

    W.W. Batenburg (Wendy); R.J.A. de Bruin (René); J.M. van Gool (Jeanette); D. Müller (Dominik); M. Bader (Michael); G. Nguyen (Genevieve); A.H.J. Danser (Jan)

    2008-01-01

    textabstractRenin inhibition with aliskiren has been reported to cause a greater rise in renin than other types of renin-angiotensin system blockade, thereby potentially leading to angiotensin generation or stimulation of the human (pro)renin receptor (h(P)RR). Here we studied whether this rise in

  4. Diuretics prevent Rho-kinase activation and expression of profibrotic/oxidative genes in the hypertensive aortic wall.

    Science.gov (United States)

    Araos, Patricio; Mondaca, David; Jalil, Jorge E; Yañez, Cristián; Novoa, Ulises; Mora, Italo; Ocaranza, María Paz

    2016-12-01

    Diuretics are current antihypertensive drugs since they reduce blood pressure and cardiovascular risk. Increased vascular tone is modulated in a relevant way by the RhoA/Rho-kinase (ROCK) pathway, by acting on vascular smooth muscle cell contraction. This pathway has also proremodeling vascular effects. There are few data on the role of diuretics on both vascular ROCK activation and on proremodeling effects. We assessed the effects of hydrochlorothiazide (HCTZ) and spironolactone (spiro) alone and in combination with the ROCK inhibitor fasudil (FAS) on ROCK activation, gene expression of proremodeling markers and on hypertrophy in the aortic wall of hypertensive rats. Deoxycorticosterone acetate (DOCA)-salt hypertensive rats (male, Sprague-Dawley) were randomized to the specific ROCK inhibitor FAS, HCTZ, spiro or the combinations of FAS/HCTZ or FAS/spiro for 3 weeks. At the end of the study, ROCK activation (by western blot), gene expression of proremodeling markers (by reverse transcription polymerase chain reaction, RT-PCR) and vascular hypertrophy (by morphometry) were determined in the aortic wall. All treatments significantly reduced blood pressure. In the DOCA rats the p-myosin phosphatase target protein-1 (MYPT1)/t-MYPT1 ratio, index of ROCK activation was higher by 2.8 fold (p diuretics alone or in combination with FAS. In the aortic wall, both HCTZ and spiro in antihypertensive doses reduce ROCK activation, subsequent expression of genes that promote vascular remodeling and hypertrophy in this experimental model of hypertension. These effects could explain some of their clinical benefits in hypertensive patients. © The Author(s), 2016.

  5. Hemorrhage Control for Major Traumatic Vascular Injuries

    Science.gov (United States)

    2016-10-01

    and it is unclear if this contributed to the high (46%) mortality in OPEN patients with thoracic aortic injury. Intra- abdominal arterial hemorrhage...Endovascular therapy for overcoming challenges presented with blunt abdominal aortic injury. Vascular and endovascular surgery 2012;46:329-331. 23...systematically define the clinical and logistical issues surrounding traditional open vascular surgery and catheter-based hemorrhage control. The

  6. Reinforced aortic root reconstruction for acute type A aortic dissection involving the aortic root

    Directory of Open Access Journals (Sweden)

    Han Qing-qi

    2013-06-01

    Full Text Available OBJECTIVE: There are debates regarding the optimal approach for AAAD involving the aortic root. We described a modified reinforced aortic root reconstruction approach for treating AAAD involving the aortic root. METHODS: A total of 161 patients with AAAD involving the aortic root were treated by our modified reinforced aortic root reconstruction approach from January 1998 to December 2008. Key features of our modified approach were placement of an autologous pericardial patch in the false lumen, lining of the sinotubular junction lumen with a polyester vascular ring, and wrapping of the vessel with Teflon strips. Outcome measures included post-operative mortality, survival, complications, and level of aortic regurgitation. RESULTS: A total of 161 patients were included in the study (mean age: 43.3 1 15.5 years. The mean duration of follow-up was 5.1 1 2.96 years (2-12 years. A total of 10 (6.2% and 11 (6.8% patients died during hospitalization and during follow-up, respectively. Thirty-one (19.3% patients experienced postoperative complications. The 1-, 3-, 5-, and 10-year survival rates were 99.3%, 98%, 93.8%, and 75.5%, respectively. There were no instances of recurrent aortic dissection, aortic aneurysm, or pseudoaneurysm during the entire study period. The severity of aortic regurgitation dramatically decreased immediately after surgery (from 28.6% to 0% grade 3-4 and thereafter slightly increased (from 0% to 7.2% at 5 years and 9.1% at 10 years. CONCLUSION: This modified reinforced aortic root reconstruction was feasible, safe and durable/effective, as indicated by its low mortality, low postoperative complications and high survival rate.

  7. Effect of pioglitazone on the calcification of rat vascular smooth muscle cells through the downregulation of the Wnt/β‑catenin signaling pathway.

    Science.gov (United States)

    Gao, Min; Chen, Tianlei; Wu, Lin; Zhao, Xiufen; Mao, Huijuan; Xing, Changying

    2017-11-01

    The aim of the present study was to investigate the effect and possible mechanism of pioglitazone (PIO) on the calcification of rat vascular smooth muscle cells (VSMCs) in vitro. β‑glycerophosphate (β‑GP; 10 mmol/l) was used to induce calcification of VSMCs treated with a range of concentrations (5, 10, 15 and 20 µmol/l) of PIO for 12 days. Calcium deposits were revealed by Alizarin red staining. Extracellular calcium content was detected using a calcium assay kit. Western blotting was used to measure the expression of α‑smooth muscle actin (α‑SMA), runt‑related transcription factor 2 (Runx2), bone morphogenetic protein‑2 (BMP2), β‑catenin, glycogen synthase kinase‑3β (GSK‑3β), phosphorylated (p)‑GSK‑3β and cyclin‑D1. A total of 10 mmol/l β‑GP, 20 µmol/l PIO and 20 µmol/l peroxisome proliferator‑activated receptor γ (PPAR γ) antagonist GW9662, was added to the cell culture media. The changes of the above indexes were observed. The calcium content in the calcification group, treated with high phosphorus, increased significantly compared with the controls (P<0.05) and all different concentrations of PIO reduced extracellular calcium content (P<0.05). Alizarin red staining was positive in calcified VSMCs and PIO (20 µmol/l) intervention group was almost negative. The expressions of Runx2, β‑catenin, p‑GSK‑3β, BMP2 and cyclin‑D1 increased significantly in the calcification group, and treatment with 20 µmol/l PIO downregulated the expression of all the above proteins, while upregulating the expression of α‑SMA. The PPAR γ antagonist GW9662 could partly inhibit the effect of PIO on calcified VSMCs. The results of the present study indicated that PIO can alleviate the calcification of rat aortic VSMCs induced by β‑GP via inhibiting the activity of the Wnt/β‑catenin signaling pathway.

  8. [Effects of cigarette smoke exposure on pulmonary vascular intercellular adhesion molecule-1 and matrix metalloproteinase-9 in rats].

    Science.gov (United States)

    Hu, Xiao-Yun; Zhang, Hong-Li; Xu, Jian-Ying; Wang, Chen

    2009-09-01

    To understand the effects of cigarette smoke exposure and smoke cessation on the structure, inflammation and remodeling of pulmonary blood vessels in rats. Thirty-two male Wistar rats were randomly divided into a control group, a smoke exposure group 1 (low dose smoke), a smoke exposure group 2 (high dose smoke) and a smoke cessation group, with 8 rats in each group. The ratio of pulmonary vascular wall thickness/vascular external diameter (WT%) and the ratio of pulmonary vascular wall area/total pulmonary vascular area (WA%) were measured by the image analysis system. The expressions of pulmonary vascular ICAM-1 and MMP-9 protein and mRNA were detected respectively by enzyme linked immunosorbent assay (ELISA) and in situ hybridization techniques. WT% and WA% increased significantly in the smoke exposure group 1 [(15.3 +/- 2.1)%, (41 +/- 7)%] and smoke exposure group 2 [(18.0 +/- 2.0)%, (50 +/- 7)%] compared to those of the control group [(10.4 +/- 2.0)%, (30 +/- 4)%] (q = 4.93 - 11.16, P smoke cessation group [(11.0 +/- 1.3)%, (35 +/- 5)%] decreased significantly compared to those of the smoke exposure group 2 (q = 6.74 - 10.29, P pulmonary vascular ICAM-1 protein and mRNA increased significantly in the smoke cessation group, the smoke exposure group 1 and the smoke exposure group 2 [(7.9 +/- 3.2 and 6.2 +/- 3.0), (12.9 +/- 2.3 and 10.3 +/- 2.2), (19.2 +/- 2.3 and 18.3 +/- 2.4)] compared to those of the control group (4.7 +/- 2.3 and 2.7 +/- 1.7) (q = 3.28 - 15.76, P smoke cessation group compared to those of the smoke exposure groups (q = 3.85 - 12.46, P smoke cessation group, smoke exposure group 1 and smoke exposure group 2 [(12.0 +/- 2.8 and 7.0 +/- 3.4), (16.1 +/- 2.8 and 12.5 +/- 1.8), (22.5 +/- 3.5 and 20.0 +/- 3.1)] compared to those of the control group (7.8 +/- 3.0 and 3.2 +/- 2.8) (q = 3.19 - 14.22, P smoke cessation group compared to those of the smoke exposure groups (q = 3.68 - 11.03, P Cigarette smoke exposure caused pulmonary vascular wall

  9. Calcium channel blockers, more than diuretics, enhance vascular protective effects of angiotensin receptor blockers in salt-loaded hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Eiichiro Yamamoto

    Full Text Available The combination therapy of an angiotensin receptor blocker (ARB with a calcium channel blocker (CCB or with a diuretic is favorably recommended for the treatment of hypertension. However, the difference between these two combination therapies is unclear. The present work was undertaken to examine the possible difference between the two combination therapies in vascular protection. Salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP were divided into 6 groups, and they were orally administered (1 vehicle, (2 olmesartan, an ARB, (3 azelnidipine, a CCB, (4 hydrochlorothiazide, a diuretic, (5 olmesartan combined with azelnidipine, or (6 olmesartan combined with hydrochlorothiazide. Olmesartan combined with either azelnidipine or hydrochlorothiazide ameliorated vascular endothelial dysfunction and remodeling in SHRSP more than did monotherapy with either agent. However, despite a comparable blood pressure lowering effect between the two treatments, azelnidipine enhanced the amelioration of vascular endothelial dysfunction and remodeling by olmesartan to a greater extent than did hydrochlorothiazide in salt-loaded SHRSP. The increased enhancement by azelnidipine of olmesartan-induced vascular protection than by hydrochlorothiazide was associated with a greater amelioration of vascular nicotinamide adenine dinucleotide phosphate (NADPH oxidase activation, superoxide, mitogen-activated protein kinase activation, and with a greater activation of the Akt/endothelial nitric oxide synthase (eNOS pathway. These results provided the first evidence that a CCB potentiates the vascular protective effects of an ARB in salt-sensitive hypertension, compared with a diuretic, and provided a novel rationale explaining the benefit of the combination therapy with an ARB and a CCB.

  10. [Effects of low molecular weight heparin on the inflammatory response and vascular injury in rat after electric burn].

    Science.gov (United States)

    Jiang, Nanhong; Xie, Weiguo; Wang, Hui; Jin, Dongmei; Tan, Hong; Zhao, Chaoli

    2014-04-01

    To observe the effects of low molecular weight heparin (LMWH) on the inflammatory response and vascular injury in rat after electric burn. A homemade regulator and transformer apparatus was used to reproduce the model of electric burn (0.5 cm×0.5 cm in size) with depth from full-thickness to full-thickness skin plus muscle and bone on the middle of the inside of right hind limb in 60 Wistar rats. The open wounds were covered with 20 g/L sulfadiazine silver paste immediately after injury. The wound condition was observed every day. The injured rats were divided into group LMWH and control group (C) according to the random number table, with 30 rats in each group. Rats in group LMWH were given subcutaneous injection of LMWH (1 U/g) in abdominal wall, 2 times a day. No other treatment was given in rats in group C. On post burn day (PBD) 3, 5, and 10, 10 rats respectively of two groups were sacrificed. The damaged tissue of wound and that around the wound (1.0 cm×0.5 cm in size) were excised, and heart blood was obtained. The pathological changes and thrombosis in damaged tissue were observed with HE, Masson, and aldehyde fuchsin staining, and the thrombosis rate was calculated. Serum contents of TNF-α and endothelin-1 were determined with ELISA. The mRNA expression of TNF-α in damaged tissue was detected with RT-PCR. Data were processed with Levene homogeneity test, analysis of variance of factorial design, LSD- t test, SNK- q test, and Friedman M nonparametric test. (1) The injured limb of rats was obviously swollen after electric burn, which reached deeply to the muscle and bone. Compared with those of group C, the swelling of rats subsided slightly faster and the inflammatory response was lighter in group LMWH at each time point. (2) The necrosis of damaged tissue and profuse infiltration of inflammatory cells were observed. Dilatation of blood vessels, congestion and thrombosis, and swelling, necrosis, and desquamation of vascular endothelial cells were

  11. Phenotypic Modulation of Mesenteric Vascular Smooth Muscle Cells from Type 2 Diabetic Rats is Associated with Decreased Caveolin-1 Expression

    Directory of Open Access Journals (Sweden)

    Maria Alicia Carrillo-Sepulveda

    2014-10-01

    Full Text Available Aims: Diabetes-induced vascular complications are associated with vascular smooth muscle cell (VSMC phenotypic modulation, switching from a contractile to a synthetic-proliferative phenotype. Loss of caveolin-1 is involved with proliferation of VSMCs. We tested the hypothesis that mesenteric VSMCs from type 2 diabetic Goto-Kakizaki (GK rat undergo phenotypic modulation and it is linked to decreased caveolin-1 expression. Methods: VSMCs were isolated from mesenteric arteries from GK rats and age-matched control Wistar rats. Western blotting was used to determine expression of target proteins such as caveolin-1, calponin (marker of differentiation, and proliferating cell nuclear antigen (PCNA, marker of proliferation. In addition, we measured intracellular reactive oxygen species (ROS production using H2DCF-DA and activation of extracellular signal-regulated kinase (ERK1/2 by western blotting in VSMCs from GK stimulated with lipopolysaccharide (LPS, an endotoxin upregulated in diabetes. Results: Mesenteric VSMCs from diabetic GK rats exhibited decreased caveolin-1 and calponin expression and increased PCNA expression compared to control. Increased levels of ROS and phospho-ERK1/2 expression were also found in GK VSMCs. LPS augmented ROS and phosphorylated ERK1/2 levels to a greater extent in GK VSMCs than in control. Likewise, high glucose decreased caveolin-1 and calponin expression, increased PCNA expression and augmented ROS production in control mesenteric VSMCs. Conclusion: These results suggest that mesenteric VSMCs from diabetic GK rats undergo phenotypic modulation and it is associated with decreased caveolin-1 expression. These alterations may be due to enhanced inflammatory stimuli and glucose levels present in diabetic milieu.

  12. Blueberry juice causes potent relaxation of rat aortic rings via the activation of potassium channels and the H₂S pathway.

    Science.gov (United States)

    Horrigan, Louise A; Holohan, Catherine A; Lawless, Gráinne A; Murtagh, Melissa A; Williams, Carmel T; Webster, Christina M

    2013-02-26

    The objective of this study was to investigate the in vitro effects of blueberry juice on healthy rat aortic rings, and to explore the roles of potassium channels and of the hydrogen sulphide (H(2)S) pathway in mediating the effects of blueberry juice. Firstly, the antioxidant capacity of blueberry juice was compared to other popular juice drinks using the Folin-Ciocalteu and the DPPH assays. Blueberry juice had significantly higher total polyphenol content than any of the other drinks studied (p blueberry juice on noradrenaline-contracted aortic rings was then observed, and the juice caused significant inhibition of noradrenaline-induced contractions (p blueberry juice (p blueberry juice (p blueberry juice has potent vasorelaxing properties, and thus may be a useful dietary agent for the prevention and treatment of hypertension. This study also provides strong evidence that Kv channels and the CSE/H(2)S pathway may be responsible, at least in part, for mediating the effects of blueberry juice.

  13. Vascular smooth muscle cells express the alpha(1A) subunit of a P-/Q-type voltage-dependent Ca(2+)Channel, and It is functionally important in renal afferent arterioles

    DEFF Research Database (Denmark)

    Hansen, Pernille B. Lærkegaard; Jensen, Boye L.; Andreasen, D

    2000-01-01

    in rat aorta, brain, aortic smooth muscle cells (A7r5), VSMCs, and mesangial cells. Immunolabeling with an anti-alpha(1A) antibody was positive in acid-macerated, microdissected preglomerular vessels and in A7r5 cells. Patch-clamp experiments on aortic A7r5 cells showed 22+/-4% (n=6) inhibition of inward...... and Southern blotting analysis, mRNA encoding the alpha(1A) subunit was detected in microdissected rat preglomerular vessels and vasa recta, in cultures of rat preglomerular vascular smooth muscle cells (VSMCs), and in cultured rat mesangial cells. With immunoblots, alpha(1A) subunit protein was demonstrated...... preglomerular resistance vessels and aorta, as well as mesangial cells, and that P-type VDCCs contribute to Ca(2+) influx in aortic and renal VSMCs and are involved in depolarization-mediated contraction in renal afferent arterioles....

  14. ADP-Ribosyl cyclase in rat vascular smooth muscle cells: properties and regulation.

    Science.gov (United States)

    de Toledo, F G; Cheng, J; Liang, M; Chini, E N; Dousa, T P

    2000-06-09

    We investigated whether ADP-ribosyl cyclase (ADPR-cyclase) in rat vascular smooth muscle cells (VSMCs) has enzymatic properties that differ from the well-characterized CD38-antigen ADPR-cyclase, expressed in HL-60 cells. ADPR-cyclase from VSMCs, but not CD38 ADPR-cyclase from HL-60 cells, was inhibited by gangliosides (10 micromol/L) GT(1B), GD(1), and GM(3). Preincubation of membranes from CD38 HL-60 cells, but not from VSMCs, with anti-CD38 antibodies increased ADPR-cyclase activity; CD38 antigen was detected both in VSMCs and in HL-60 cells. ADPR-cyclase in VSMC membranes was more sensitive than CD38 HL-60 ADPR-cyclase to inactivation by N-endoglycosidase F and to thermal inactivation at 45 degrees C. The specific activity of ADPR-cyclase in membranes from VSMCs was >20-fold higher than in membranes from CD38 HL-60 cells. Most importantly, VSMC ADPR-cyclase was inhibited by Zn(2+) and Cu(2+) ions; the inhibition by Zn(2+) was dose dependent, noncompetitive, and reversible by EDTA. In contrast, Zn(2+) stimulated the activity of CD38 HL-60 ADPR-cyclase and other known types of ADPR-cyclases. Retinoids act either via the nuclear receptor retinoic acid receptor or retinoid X receptor, including all-trans retinoic acid (atRA), and panagonist 9-cis-retinoic acid-upregulated VSMC ADPR-cyclase; the stimulatory effect of atRA was blocked by actinomycin D and cycloheximide. 1,25(OH)(2)-Vitamin D(3) (calciferol) stimulated VSMC ADPR-cyclase dose dependently at subnanomolar concentrations (ED(50) congruent with 56 pmol/L). Oral administration of atRA to rats resulted in an increase of ADPR-cyclase activity in aorta ( congruent with+60%) and, to a lesser degree, in myocardium of left ventricle (+18%), but atRA had no effect on ADPR-cyclases in lungs, spleen, intestinal smooth muscle, skeletal muscle, liver, or testis. Administration of 3,5,3'-triiodothyronine (T(3)) to rats resulted in an increase of ADPR-cyclase activity in aorta ( congruent with+89%), but not in liver or

  15. Estudio comparativo de microsutura vascular en ratas: punto simple y punto de colchonero horizontal Comparative study about vascular microsurgery on rats: classic interrupted suture versus horizontal mattress suture

    Directory of Open Access Journals (Sweden)

    C. Casado Sánchez

    2009-09-01

    Full Text Available La Microcirugía es la técnica empleada para la realización de la microanastomosis vascular. El objetivo del presente estudio es comparar dos tipos de técnicas de microsutura: los puntos simples clásicos, de empleo habitual en la microcirugía vascular, y los puntos de colchonero horizontales, no evaluados habitualmente para este tipo de cirugía. Fueron intervenidas 20 ratas albinas de la cepa Wistar (peso medio de 250 - 300 gr. bajo anestesia general; realizamos sección transversal en la arteria femoral, procediendo a su reparación microquirúrgica inmediata. Se establecieron 2 grupos de animales: en el grupo A (n=10, la microsutura se hizo mediante 6 puntos sueltos simples, y en el grupo B (n=10, empleando 3 puntos de colchonero horizontal. Comprobamos la patencia en el desclampado inmediato y tras una hora del desclampado (para ambas técnicas fue positiva en el 100% de los casos, y la hemorragia en ambos tiempos (se registró un único caso de sangrado en el postoperatorio inmediato en el grupo B, que requirió la revisión de la microsutura. El tiempo medio de ejecución de la sutura en el grupo B, 15 minutos aproximadamente, fue más corto que en el grupo A, 21 minutos aproximadamente, diferencia estadísticamente significativa (p Microsurgery is the procedure of choice for vascular microanastamoses. The objective of this study was to compare two types of suture techniques: classic interrupted suture anastomoses, commonly used for vascular anastamoses in microsurgery, and another technique using horizontal mattress sutures, rarely evaluated in this type of surgery. Twenty albino Wistar rats were operated (average weight: 250 - 300 gr. under general anaesthesia. A transverse section of the femoral artery was performed and immediately followed by an anastamoses. The animals were placed into two groups of ten. The classic 6 interrupted suture anastomoses technique was performed in group A (n = 10 and another technique using 3

  16. HIV infection and aortic stiffness.

    Science.gov (United States)

    Leite, Luisa Helena Maia; Cohen, Ariel; Boccara, Franck

    People living with human immunodeficiency virus (HIV) infection and receiving antiretroviral therapy now have the same life expectancy as the general population. However, they have a higher risk of atherosclerotic cardiovascular events because of a complex and polyfactorial vasculopathy, combining the effects of antiretroviral therapy, the HIV virus itself, immune activation, chronic inflammation and metabolic disturbances. Whether people living with HIV infection experience increased vascular aging compared with the general population remains controversial. To summarize current knowledge of the association between HIV infection and aortic stiffness as a marker of vascular aging. This review included 18 clinical studies in adult populations, published between 2009 and 2016, and identified on PubMed/MEDLINE or other databases. Search terms were aortic stiffness, arterial stiffness, vascular aging, pulse wave velocity and HIV. All 18 studies were observational, and compared groups infected (HIV+) and not infected (HIV-) with HIV. Ten studies (55%) reported no significant differences in aortic stiffness between HIV+ groups and age-matched HIV- control groups. The main reported determinants of aortic stiffness were age, blood pressure, smoking, metabolic syndrome and HIV-related variables, including CD4/CD8 ratio, current T-CD4 count < 200/mm 3 and nadir T-CD4+ count < 200/mm 3 . We found discordant results regarding whether HIV+ patients had increased aortic stiffness compared with HIV- controls. However, HIV-related conditions were associated with vascular health. This association has been confirmed in recent prospective studies. There is emerging evidence that HIV itself and immune activity affect vascular health and the large arteries. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Effect of dehydroepiandrosterone (DHEA) on memory and brain derived neurotrophic factor (BDNF) in a rat model of vascular dementia.

    Science.gov (United States)

    Sakr, H F; Khalil, K I; Hussein, A M; Zaki, M S A; Eid, R A; Alkhateeb, M

    2014-02-01

    The effect of dehydroepiandrosterone (DHEA) on memory and cognition in experimental animals is well known, but its efficacy in clinical dementia is unproven. So, the aim of the present study was to investigate the effect of DHEA on learning and memory activities in a rat model of vascular dementia (VD). Forty-eight male rats that positively passed the holeboard memory test were chosen for the study before bilateral permanent occlusion of the common carotid artery. They were divided into four groups (n=12, each) as follows (i) untreated control, (ii) rats exposed to surgical permanent bilateral occlusion of the common carotid arteries (BCCAO) leading to chronic cerebral hypoperfusion, (iii) rats exposed to BCCAO then received DHEA (BCCAO + DHEA) and (i.v.) rats exposed to BCCAO then received donepezil (BCCAO + DON). Holeboard memory test was used to assess the time, latency, working memory and reference memory. Central level of acetylcholine, norepinephrine and dopamine in the hippocampus were measured. Furthermore, the expression of brain derived neurotrophic factor (BDNF) in the hippocampus was determined. Histopathological studies of the cerebral cortex and transmission electron microscope of the hippocampus were performed. BCCAO decreased the learning and memory activities in the holeboard memory. Also, it decreased the expression of BDNF as well as the central level of acetylcholine, noradrenaline and dopamine as compared to control rats. Treatment with DHEA and donepezil increased the working and reference memories, BDNF expression as well as the central acetylcholine in the hippocampus as compared to BCCAO rats. DHEA produced neuroprotective effects through increasing the expression of BDNF as well as increasing the central level of acetylcholine and catecholamines which are non-comparable to donepezil effects.

  18. Polyphenol-containing azuki bean (Vigna angularis) seed coats attenuate vascular oxidative stress and inflammation in spontaneously hypertensive rats.

    Science.gov (United States)

    Mukai, Yuuka; Sato, Shin

    2011-01-01

    We investigated the effects of azuki bean (Vigna angularis) seed coats (ABSC), which contain polyphenols, on the vascular oxidative stress and inflammation associated with hypertension. Spontaneously hypertensive rats (SHR) and control normotensive Wistar-Kyoto (WKY) rats were divided into 2 groups each. One group was fed 0% ABSC; the other, a 1.0% ABSC-containing diet. Tail systolic blood pressure (SBP) was examined throughout ABSC treatment. At 8 weeks, vascular superoxide (O(2)(-)) production was measured by lucigenin-enhanced chemiluminescence. mRNA expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, macrophage chemoattractant protein-1 (MCP-1) and its receptor C-C chemokine receptor 2 (CCR2) in the aorta were analyzed by reverse transcriptase-polymerase chain reaction. Protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined by western blotting. Polyphenol-containing ABSC suppressed the elevation of SBP throughout the treatment period. The NADPH-stimulated O(2)(-) level decreased significantly in the aorta of ABSC-treated SHR compared with the level of untreated SHR. The p47phox and Nox4 mRNA expression increased significantly in untreated SHR compared with that in WKY rats. Conversely, the level of p47phox mRNA was significantly lower in ABSC-treated SHR than in untreated SHR. The protein abundance of both iNOS and COX-2 was significantly decreased in the aorta of the ABSC-treated SHR compared with this abundance in untreated SHR. The MCP-1 and CCR2 mRNA expressions increased in untreated SHR, and these levels were significantly lower in ABSC-treated SHR. In conclusion, our results suggested that polyphenol-containing ABSC could attenuate vascular oxidative stress and inflammation during the progression of hypertension, and this may lead to an improvement in hypertension. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Characterization of the muscarinic receptor subtype mediating vasodilation in the rat perfused mesenteric vascular bed preparation

    NARCIS (Netherlands)

    Hendriks, M. G.; Pfaffendorf, M.; van Zwieten, P. A.

    1992-01-01

    1. The nature of the muscarinic receptor subtype mediating endothelium-dependent vascular relaxation was investigated in the perfused mesenteric vascular bed preparation which is a model for resistance vessels. 2. After methoxamine-induced vasoconstriction the vessels were dilated with

  20. Genistein prevents hyperglycemia-induced monocyte adhesion to human aortic endothelial cells through preservation of the cAMP signaling pathway and ameliorates vascular inflammation in obese diabetic mice.

    Science.gov (United States)

    Babu, Pon Velayutham Anandh; Si, Hongwei; Fu, Zhuo; Zhen, Wei; Liu, Dongmin

    2012-04-01

    Hyperglycemia-induced vascular inflammation resulting in the enhanced monocyte-endothelial cell (EC) interaction is the key event in the pathogenesis of atherosclerosis in diabetes. Here, we investigated the effect of isoflavone genistein on hyperglycemia-stimulated vascular inflammation. Human aortic EC (HAEC) were pretreated with genistein before the addition of high glucose (HG; 25 mmol/L) for 48 h. Genistein at a physiological concentration (0.1 μmol/L) significantly inhibited HG-induced adhesion of monocytes to HAEC and suppressed endothelial production of monocyte chemotactic protein-1 (MCP-1) and IL-8. Inhibition of adenylate cyclase or protein kinase A (PKA) significantly attenuated the antiadhesion effect of genistein. Consistently, genistein improved HG-impaired intracellular cAMP production and PKA activity in HAEC. Six-week-old diabetic db/db mice were untreated (db/db) or treated with a diet containing 1 g genistein/kg diet (db/db+G) for 8 wk. Their nondiabetic db/+ mice were used as normal controls. Circulating concentrations of MCP-1/JE and KC were significantly greater, whereas IL-10 concentrations were lower in db/db mice than those in normal mice. Dietary supplementation of genistein did not normalize but significantly suppressed the elevated serum concentrations of MCP-1/JE from 286 ± 30 ng/L to 181 ± 35 ng/L and KC from 321 ± 21 ng/L to 232 ± 20 ng/L while increasing that of IL-10 from 35 ± 4 ng/L to 346 ± 35 ng/L in db/db+G mice. Further, genistein treatment suppressed diabetes-induced adhesion of monocytes to EC by 87% and endothelial secretion of adhesion molecules. We conclude that genistein improves diabetes-caused vascular inflammation, which may be mediated through promoting the cAMP/PKA pathway.

  1. Genistein Prevents Hyperglycemia-Induced Monocyte Adhesion to Human Aortic Endothelial Cells through Preservation of the cAMP Signaling Pathway and Ameliorates Vascular Inflammation in Obese Diabetic Mice123

    Science.gov (United States)

    Babu, Pon Velayutham Anandh; Si, Hongwei; Fu, Zhuo; Zhen, Wei; Liu, Dongmin

    2012-01-01

    Hyperglycemia-induced vascular inflammation resulting in the enhanced monocyte-endothelial cell (EC) interaction is the key event in the pathogenesis of atherosclerosis in diabetes. Here, we investigated the effect of isoflavone genistein on hyperglycemia-stimulated vascular inflammation. Human aortic EC (HAEC) were pretreated with genistein before the addition of high glucose (HG; 25 mmol/L) for 48 h. Genistein at a physiological concentration (0.1 μmol/L) significantly inhibited HG-induced adhesion of monocytes to HAEC and suppressed endothelial production of monocyte chemotactic protein-1 (MCP-1) and IL-8. Inhibition of adenylate cyclase or protein kinase A (PKA) significantly attenuated the antiadhesion effect of genistein. Consistently, genistein improved HG-impaired intracellular cAMP production and PKA activity in HAEC. Six-week-old diabetic db/db mice were untreated (db/db) or treated with a diet containing 1 g genistein/kg diet (db/db+G) for 8 wk. Their nondiabetic db/+ mice were used as normal controls. Circulating concentrations of MCP-1/JE and KC were significantly greater, whereas IL-10 concentrations were lower in db/db mice than those in normal mice. Dietary supplementation of genistein did not normalize but significantly suppressed the elevated serum concentrations of MCP-1/JE from 286 ± 30 ng/L to 181 ± 35 ng/L and KC from 321 ± 21 ng/L to 232 ± 20 ng/L while increasing that of IL-10 from 35 ± 4 ng/L to 346 ± 35 ng/L in db/db+G mice. Further, genistein treatment suppressed diabetes-induced adhesion of monocytes to EC by 87% and endothelial secretion of adhesion molecules. We conclude that genistein improves diabetes-caused vascular inflammation, which may be mediated through promoting the cAMP/PKA pathway. PMID:22399524

  2. Effects of high-sodium intake on systemic blood pressure and vascular responses in spontaneously diabetic WBN/Kob-Lepr(fa/fa) rats.

    Science.gov (United States)

    Takagi, Yoshiichi; Kadowaki, Haruno; Kobayashi, Ikumi; Ito, Kaoru; Ito, Katsuaki; Shirai, Mitsuyuki; Asai, Fumitoshi

    2017-02-01

    The prevalence of type 2 diabetes mellitus (T2DM) and hypertension has markedly increased worldwide. The purpose of the present study was to examine the effects of a high-salt intake on the systolic blood pressure (SBP) and vascular responses in WBN/Kob-Lepr(fa/fa) (WBKDF) rats, a new spontaneous animal model of T2DM. Male WBKDF rats and age-matched Wistar rats at 6 weeks of age were each divided into two groups and fed either a normal-sodium (NS, 0.26%) diet or high-sodium (HS, 8%) diet for 14 weeks: (i) Wistar rats on NS diet (Wistar-NS); (ii) Wistar rats on HS diet (Wistar-HS); (iii) WBKDF rats on NS diet (WBKDF-NS); (iv) WBKDF rats on HS diets (WBKDF-HS). Neither WBKDF-NS nor Wistar-NS rats showed significant changes in SBP throughout the experiment, but both WBKDF-HS and Wistar-HS exhibited significant elevation of SBP, which was more prominent (Psodium ions were observed in WBKDF-HS than in Wistar-HS. The current study demonstrated that WBKDF-HS rats developed salt-sensitive hypertension associated with vascular dysfunction. The WBKDF rat may be a useful model for investigating the etiology of hypertension with T2DM. © 2016 The Authors. Clinical and Experimental Pharmacology and Physiology Published by John Wiley & Sons Australia, Ltd.

  3. Effect of exercise-induced neurogenesis on cognitive function deficit in a rat model of vascular dementia.

    Science.gov (United States)

    Choi, Dong-Hee; Lee, Kyoung-Hee; Lee, Jongmin

    2016-04-01

    Chronic cerebral hypoperfusion (CCH) is strongly correlated with progressive cognitive decline in neurological diseases, such as vascular dementia (VaD) and Alzheimer's disease. Exercise can enhance learning and memory, and delay age-related cognitive decline. However, exercise-induced hippocampal neurogenesis in experimental animals submitted to CCH has not been investigated. The present study aimed to investigate whether hippocampal neurogenesis induced by exercise can improve cognitive deficit in a rat model of VaD. Male Wistar rats (age, 8 weeks; weight, 292±3.05 g; n=12-13/group) were subjected to bilateral common carotid artery occlusion (2VO) or sham‑surgery and each group was then subdivided randomly into no exercise and treadmill exercise groups. Exercise groups performed treadmill exercise daily at 15 m/min for 30 min for 4 weeks from the third to the seventh week after 2VO. It was demonstrated that the number of neural progenitor cells and mature neurons in the subgranular zone of 2VO rats was increased by exercise, and cognitive impairment in 2VO rats was attenuated by treadmill exercise. In addition, mature brain‑derived neurotrophic factor (BDNF) levels in the hippocampus were increased in the exercise groups. Thus the present study suggests that exercise delays cognitive decline by the enhancing neurogenesis and increasing BDNF expression in the context of VaD.

  4. Effect of Selective 5-HT6R Agonist on Expression of 5-HT Receptor and Neurotransmitter in Vascular Dementia Rats.

    Science.gov (United States)

    Yu, Haining; Chen, Tao; Zhou, Li; Tang, Jiyou

    2017-02-15

    BACKGROUND 5-HT6 receptor (5-HT6R) has pluripotent roles regulating secretion of neurotransmitters. However, whether 5-HT6R is involved in the development of vascular dementia (VD) remains unclear. To evaluate the role and mechanism of 5-HT6R in VD, this study established a rat VD model to evaluate the effect of selective 5-HT6R agonist on the expression of 5-HT6R mRNA and neurotransmitter. MATERIAL AND METHODS Eighty healthy male SD rats (7 weeks old) were randomly assigned to sham, model, 5-HT6R agonist, and placebo groups (N=20 each). A rat VD model was generated by permeant bilateral ligation of the common carotid artery. 5-HT6R agonist, placebo, or saline were given intraperitoneally for 4 weeks. The Morris water maze was utilized to test learning and memory function. Brains were extracted to separate the cortex and hippocampal tissues, in which glutamate and g-aminobutyric acid (GABA) levels were analyzed. mRNA and protein levels of 5-HT6R were determined by RT-PCR and immunohistochemistry (IHC), respectively. RESULTS Model rats had longer escape latency and fewer crossing platform times. Contents of DA, Glu, GABA, and Ach were lowered in cortical and hippocampal tissues, and 5-HT6R expression was suppressed (pneurotransmitter levels in brain regions.

  5. Effect of exercise-induced neurogenesis on cognitive function deficit in a rat model of vascular dementia

    Science.gov (United States)

    CHOI, DONG-HEE; LEE, KYOUNG-HEE; LEE, JONGMIN

    2016-01-01

    Chronic cerebral hypoperfusion (CCH) is strongly correlated with progressive cognitive decline in neurological diseases, such as vascular dementia (VaD) and Alzheimer's disease. Exercise can enhance learning and memory, and delay age-related cognitive decline. However, exercise-induced hippocampal neurogenesis in experimental animals submitted to CCH has not been investigated. The present study aimed to investigate whether hippocampal neurogenesis induced by exercise can improve cognitive deficit in a rat model of VaD. Male Wistar rats (age, 8 weeks; weight, 292±3.05 g; n=12–13/group) were subjected to bilateral common carotid artery occlusion (2VO) or sham-surgery and each group was then subdivided randomly into no exercise and treadmill exercise groups. Exercise groups performed treadmill exercise daily at 15 m/min for 30 min for 4 weeks from the third to the seventh week after 2VO. It was demonstrated that the number of neural progenitor cells and mature neurons in the subgranular zone of 2VO rats was increased by exercise, and cognitive impairment in 2VO rats was attenuated by treadmill exercise. In addition, mature brain-derived neurotrophic factor (BDNF) levels in the hippocampus were increased in the exercise groups. Thus the present study suggests that exercise delays cognitive decline by the enhancing neurogenesis and increasing BDNF expression in the context of VaD. PMID:26934837

  6. Mast cells promote lung vascular remodelling in pulmonary hypertension.

    Science.gov (United States)

    Hoffmann, J; Yin, J; Kukucka, M; Yin, N; Saarikko, I; Sterner-Kock, A; Fujii, H; Leong-Poi, H; Kuppe, H; Schermuly, R T; Kuebler, W M

    2011-06-01

    Left heart disease (LHD) frequently causes lung vascular remodelling and pulmonary hypertension (PH). Yet pharmacological treatment for PH in LHD is lacking and its pathophysiological basis remains obscure. We aimed to identify candidate mechanisms of PH in LHD and to test their relevance and therapeutic potential. In rats, LHD was induced by supracoronary aortic banding. Whole genome microarray analyses were performed, candidate genes were confirmed by RT-PCR and Western blots and functional relevance was tested in vivo by genetic and pharmacological strategies. In lungs of LHD rats, mast cell activation was the most prominently upregulated gene ontology cluster. Mast cell gene upregulation was confirmed at RNA and protein levels and remodelled vessels showed perivascular mast cell accumulations. In LHD rats treated with the mast cell stabiliser ketotifen, or in mast cell deficient Ws/Ws rats, PH and vascular remodelling were largely attenuated. Both strategies also reduced PH and vascular remodelling in monocrotaline-induced pulmonary arterial hypertension, suggesting that the role of mast cells extends to non-cardiogenic PH. In PH of different aetiologies, mast cells accumulate around pulmonary blood vessels and contribute to vascular remodelling and PH. Mast cells and mast cell-derived mediators may present promising targets for the treatment of PH.

  7. Contribution of nitric oxide synthase (NOS) activity in blood-brain barrier disruption and edema after acute ischemia/reperfusion in aortic coarctation-induced hypertensive rats.

    Science.gov (United States)

    Mohammadi, Mohammad Taghi; Shid Moosavi, Seyed Mostafa; Dehghani, Gholam Abbas

    2011-01-01

    Nitric oxide synthase (NOS) activity is increased during hypertension and cerebral ischemia. NOS inactivation reduces stroke-induced cerebral injuries, but little is known about its role in blood-brain barrier (BBB) disruption and cerebral edema formation during stroke in acute hypertension. Here, we investigated the role of NOS inhibition in progression of edema formation and BBB disruptions provoked by ischemia/reperfusion injuries in acute hypertensive rats. Rats were made acutely hypertensive by aortic coarctation. After 7 days, the rats were randomly selected for the recording of carotid artery pressure, or regional cerebral blood flow (rCBF) using laser Doppler. Ishcemia induced by 60-min middle cerebral artery occlusion (MCAO), followed by 12-h reperfusion. A single i.p. dose of L-NAME (1 mg/kg) was injected before MCAO. After evaluation of neurological disabilities, rats were slaughtered under deep anesthesia to assess cerebral infarction volume, edema, or BBB disruption. A 75-85% reduction in rCBF was occurred during MCAO which returned to pre-occluded levels during reperfusion. Profound neurological disabilities were evidenced after MCAO alongside with severe cerebral infarctions (628 ± 98 mm3), considerable edema (4.05 ± 0.52%) and extensive BBB disruptions (Evans blue extravasation, 8.46 ± 2.03 mug/g). L-NAME drastically improved neurological disabilities, diminished cerebral infarction (264 ± 46 mm3), reduced edema (1.49 ± 0.47%) and BBB disruption (2.93 ± 0.66 mug/g). The harmful actions of NOS activity on cerebral microvascular integrity are intensified by ischemia/reperfusion injuries during acute hypertension. NOS inactivation by L-NAME preserved this integrity and diminished cerebral edema.

  8. Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes

    Directory of Open Access Journals (Sweden)

    T.R. Oliveira

    2009-09-01

    Full Text Available Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR and normotensive control rat strains (WKY and NWR. Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

  9. Arginase inhibition prevents bleomycin-induced pulmonary hypertension, vascular remodeling, and collagen deposition in neonatal rat lungs.

    Science.gov (United States)

    Grasemann, Hartmut; Dhaliwal, Rupinder; Ivanovska, Julijana; Kantores, Crystal; McNamara, Patrick J; Scott, Jeremy A; Belik, Jaques; Jankov, Robert P

    2015-03-15

    Arginase is an enzyme that limits substrate L-arginine bioavailability for the production of nitric oxide by the nitric oxide synthases and produces L-ornithine, which is a precursor for collagen formation and tissue remodeling. We studied the pulmonary vascular effects of arginase inhibition in an established model of repeated systemic bleomycin sulfate administration in neonatal rats that results in pulmonary hypertension and lung injury mimicking the characteristics typical of bronchopulmonary dysplasia. We report that arginase expression is increased in the lungs of bleomycin-exposed neonatal rats and that treatment with the arginase inhibitor amino-2-borono-6-hexanoic acid prevented the bleomycin-induced development of pulmonary hypertension and deposition of collagen. Arginase inhibition resulted in increased L-arginine and L-arginine bioavailability and increased pulmonary nitric oxide production. Arginase inhibition also normalized the expression of inducible nitric oxide synthase, and reduced bleomycin-induced nitrative stress while having no effect on bleomycin-induced inflammation. Our data suggest that arginase is a promising target for therapeutic interventions in neonates aimed at preventing lung vascular remodeling and pulmonary hypertension. Copyright © 2015 the American Physiological Society.

  10. Structure, vascularization, and innervation of the mystacial pad of the rat as revealed by the lectin Griffonia simplicifolia.

    Science.gov (United States)

    Rice, F L

    1993-11-15

    The mystacial pad of the rat is endowed with rows of vibrissal follicle-sinus complexes (F-SCs) that receive a dense and rich variety of innervation, much of which is C fibers. Each F-SC consists of a follicle at the core of a spindle-shaped, encapsulated vascular sinus. Previous studies have shown that the B subunit of the lectin Griffonia simplicifolia (GSA I-B4) binds selectively to a subset of small neurons in the trigeminal ganglion and to a subset of C fibers preferentially distributed to inner lamina II and outer lamina III of nucleus caudalis in the brainstem trigeminal complex in the rat. These laminae are also a major site of termination for afferents in superficial vibrissal nerves (SVNs) that innervate the upper portion of F-SCs. To determine the peripheral distribution of the afferents that bind GSA I-B4, mystacial pads from rats were prepared for fluorescence microscopy with GSA I-B4 conjugated to rhodamine. At the neck of each F-SC, numerous circumferentially oriented bundles of fine-caliber axonal profiles were labeled in the inner conical body, which receives nearly all of its innervation from the SVNs. A sparse, random distribution of fine-caliber profiles from deep vibrissal nerves was labeled at the level of the cavernous sinus in the deep half of the F-SCs. GSA I-B4 also labeled a variety of nonneural structures. By binding to vascular linings, GSA I-B4 revealed a dense, highly organized capillary system within the mesenchymal sheath that forms the inner lining of the vascular sinuses. Thus each F-SC appears to have a closed capillary system within the open vascular sinus. Trabeculae within the lumen of the cavernous sinus were also revealed to span between the sinus capsule and the mesenchymal sheath only about midway along the length of the follicle instead of the entire deeper half, as was previously believed. in addition, GSA I-B4 bound to the surface of follicular cells preferentially in the superficial half of the F-SCs. Sweat glands

  11. Anti-atherogenic effects of the methanol extract of Sorbus cortex in atherogenic-diet rats.

    Science.gov (United States)

    Sohn, Eun Jin; Kang, Dae Gill; Mun, Yeun Ja; Woo, Won Hong; Lee, Ho Sub

    2005-08-01

    The present study was designed to examine whether the methanol extract of Sorbus commixta cortex (MSC) could prevent the development of atherosclerosis through regulating the vascular nitric oxide (NO) and endothelin-1 (ET-1) systems in atherogenic-diet rats. Our findings show that aortic NO production as well as endothelial nitric oxide synthase (ecNOS) expression was significantly decreased in atherogenic-diet rats compared with those in the control group. Aortic ET-1 expression was augmented in rats fed an atherogenic-diet while NF-kappaB p65 was upregulated. Treatment of atherogenic-diet rats with either low (100 mg/kg/d) or high (200 mg/kg/d) doses of MSC led not only to significant increases in the aortic NOS/NO system, but also to decreases in aortic ET-1 expression. The aortic expression level of NF-kappaB p65 was also attenuated in atherogenic-diet rats by chronic treatment with low or high doses of MSC. Atherogenic-diet induced increases in the expression of adhesion molecules including intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were markedly decreased by treatment with MSC. From the histopathological examination, MSC treatment was shown to lessen the thickening noted in the aortic intima and media of the atherogenic-diet rats. These results suggest that MSC affects the atherogenic process via the suppression of proinflammatory and adhesion molecules in atherogenic-diet rats, which may be, at least in part, causally related with the regulation of vasoactive systems such as the NO and ET-1 systems.

  12. Mitogenesis in cultured vascular smooth muscle cells from two rat models of hypertension in response to fetal calf serum and angiotensin II.

    Science.gov (United States)

    Millar, J A; Harris, E L; Cassie, N J

    1990-01-01

    Hypertension may result from vascular hypertrophy or hyperplasia due to enhanced growth of vascular smooth muscle cells (VSMCs), which has been demonstrated in VSMCs from spontaneously hypertensive rats (SHRs) compared to Wistar-Kyoto (WKY) rats. To determine whether this enhanced mitogenesis is peculiar to SHRs or a general phenomenon in genetic models of hypertension, we have measured indices of cell growth [3H]-thymidine uptake in VSMCs from SHRs and New Zealand genetically hypertensive (GH) rats and controls [WKY and normal Wistar (N) rats] cultured in fetal calf serum (FCS) or angiotensin II (Ang II, 0.1 microM) in either 3% heat-treated FCS or serum-free medium. SHR cell numbers increased faster in response to both mitogens compared to WKY rats. However, GH and N rat responses to FCS were the same. Ang II caused a significant but similar increase in cell numbers in both GH and N rat cells (i.e., Ang II caused hyperplasia in all four strains) but [3H]thymidine uptake was significantly greater in GH rat cells. Ang II increased the total well protein content but not protein normalized on cell number, i.e., no hypertrophic effect of Ang II was seen in these actively dividing cells. We conclude that (a) growth properties of VSMCs from rats with genetic hypertension vary between strains; the differences in growth may reflect strain-specific variation in the activity of intracellular signalling systems subserving mitogenesis; and (b) Ang II causes VSMC hyperplasia.

  13. Beneficial Effects of Calcitriol on Hypertension, Glucose Intolerance, Impairment of Endothelium-Dependent Vascular Relaxation, and Visceral Adiposity in Fructose-Fed Hypertensive Rats

    OpenAIRE

    Chu-Lin Chou; Cheng-Yoong Pang; Lee, Tony J. F.; Te-Chao Fang

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-f...

  14. Lidocaine relaxation in isolated rat aortic rings is enhanced by endothelial removal: possible role of Kv, KATP channels and A2a receptor crosstalk.

    Science.gov (United States)

    Arsyad, Aryadi; Dobson, Geoffrey P

    2016-12-03

    Lidocaine is an approved local anesthetic and Class 1B antiarrhythmic with a number of ancillary properties. Our aim was to investigate lidocaine's vasoreactivity properties in intact versus denuded rat thoracic aortic rings, and the effect of inhibitors of nitric oxide (NO), prostenoids, voltage-dependent Kv and KATP channels, membrane Na(+)/K(+) pump, and A2a and A2b receptors. Aortic rings were harvested from adult male Sprague Dawley rats and equilibrated in an organ bath containing oxygenated, modified Krebs-Henseleit solution, pH 7.4, 37 °C. The rings were pre-contracted sub-maximally with 0.3 μM norepinephrine (NE), and the effect of increasing lidocaine concentrations was examined. Rings were tested for viability after each experiment with maximally dilating 100 μM papaverine. The drugs 4-aminopyridine (4-AP), glibenclamide, 5-hydroxydecanoate, ouabain, 8-(3-chlorostyryl) caffeine and PSB-0788 were examined. All drugs tested had no significant effect on basal tension. Lidocaine relaxation in intact rings was biphasic between 1 and 10 μM (Phase 1) and 10 and 1000 μM (Phase 2). Mechanical removal of the endothelium resulted in further relaxation, and at lower concentrations ring sensitivity (% relaxation per μM lidocaine) significantly increased 3.5 times compared to intact rings. The relaxing factor(s) responsible for enhancing ring relaxation did not appear to be NO- or prostacyclin-dependent, as L-NAME and indomethacin had little or no effect on intact ring relaxation. In denuded rings, lidocaine relaxation was completely abolished by Kv channel inhibition and significantly reduced by antagonists of the MitoKATP channel, and to a lesser extent the SarcKATP channel. Curiously, A2a subtype receptor antagonism significantly inhibited lidocaine relaxation above 100 μM, but not the A2b receptor. We show that lidocaine relaxation in rat thoracic aorta was biphasic and significantly enhanced by endothelial removal, which did not appear to be NO or

  15. [Effects of ear point needle embedding therapy on memory disorder and expression of beta-amyloid protein in the rat of vascular dementia].

    Science.gov (United States)

    Lu, Yu-wei; Lü, Ming-zhuang

    2006-11-01

    To study the mechanism of auricular acupuncture for improvement of learning and memory disorders in the rat of vascular dementia (VD). The vascular dementia rat model was made by 4-vessel occlusion method. Four groups, a sham operation group, a normal control group, a model group and an auricular acupuncture group were set up. After acupuncture was given at auricular points, Brain and Kidney. Immunohistochemical analysis, behavioural observation and computer image analysis were made. Auricular acupuncture could decrease significantly the beta-amyloid protein (A beta) immunoreactivive neurons and increase its average optical density in the parietal cortex of the VD rats (P improve the learning and memory capacity of the VD model rat.

  16. Effect of glycosides of Cistanche on the expression of mitochondrial precursor protein and keratin type II cytoskeletal 6A in a rat model of vascular dementia

    Directory of Open Access Journals (Sweden)

    Yan-mei Zhang

    2017-01-01

    Full Text Available Glycosides of Cistanche (GC is a preparation used extensively for its neuroprotective effect against neurological diseases, but its mechanisms of action remains incompletely understood. Here, we established a bilateral common carotid artery occlusion model of vascular dementia in rats and injected the model rats with a suspension of GC (10 mg/kg/day, intraperitoneally for 14 consecutive days. Immunohistochemistry showed that GC significantly reduced p-tau and amyloid beta (Aβ immunoreactivity in the hippocampus of the model rats. Proteomic analysis demonstrated upregulation of mitochondrial precursor protein and downregulation of keratin type II cytoskeletal 6A after GC treatment compared with model rats that had received saline. Western blot assay confirmed these findings. Our results suggest that the neuroprotective effect of GC in vascular dementia occurs via the promotion of neuronal cytoskeleton regeneration.

  17. Reduction of advanced-glycation end products levels and inhibition of RAGE signaling decreases rat vascular calcification induced by diabetes.

    Directory of Open Access Journals (Sweden)

    Mathieu R Brodeur

    Full Text Available Advanced-glycation end products (AGEs were recently implicated in vascular calcification, through a process mediated by RAGE (receptor for AGEs. Although a correlation between AGEs levels and vascular calcification was established, there is no evidence that reducing in vivo AGEs deposition or inhibiting AGEs-RAGE signaling pathways can decrease medial calcification. We evaluated the impact of inhibiting AGEs formation by pyridoxamine or elimination of AGEs by alagebrium on diabetic medial calcification. We also evaluated if the inhibition of AGEs-RAGE signaling pathways can prevent calcification. Rats were fed a high fat diet during 2 months before receiving a low dose of streptozotocin. Then, calcification was induced with warfarin. Pyridoxamine was administered at the beginning of warfarin treatment while alagebrium was administered 3 weeks after the beginning of warfarin treatment. Results demonstrate that AGEs inhibitors prevent the time-dependent accumulation of AGEs in femoral arteries of diabetic rats. This effect was accompanied by a reduced diabetes-accelerated calcification. Ex vivo experiments showed that N-methylpyridinium, an agonist of RAGE, induced calcification of diabetic femoral arteries, a process inhibited by antioxidants and different inhibitors of signaling pathways associated to RAGE activation. The physiological importance of oxidative stress was demonstrated by the reduction of femoral artery calcification in diabetic rats treated with apocynin, an inhibitor of reactive oxygen species production. We demonstrated that AGE inhibitors prevent or limit medial calcification. We also showed that diabetes-accelerated calcification is prevented by antioxidants. Thus, inhibiting the association of AGE-RAGE or the downstream signaling reduced medial calcification in diabetes.

  18. Ambrisentan reduces pulmonary arterial hypertension but does not stimulate alveolar and vascular development in neonatal rats with hyperoxic lung injury.

    Science.gov (United States)

    Wagenaar, Gerry T M; Laghmani, El Houari; de Visser, Yvonne P; Sengers, Rozemarijn M A; Steendijk, Paul; Baelde, Hans J; Walther, Frans J

    2013-02-15

    Ambrisentan, an endothelin receptor type A antagonist, may be a novel therapeutic agent in neonatal chronic lung disease (CLD) by blocking the adverse effects of the vasoconstrictor endothelin-1, especially pulmonary arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH). We determined the cardiopulmonary effects of ambrisentan treatment (1-20 mg·kg(-1)·day(-1)) in neonatal rats with CLD in 2 models: early treatment during continuous exposure to hyperoxia for 10 days and late treatment starting on day 6 in rat pups exposed postnatally to hyperoxia for 9 days, followed by a 9-day recovery period in room air. Parameters investigated included survival, lung and heart histopathology, right ventricular function, fibrin deposition, and differential mRNA expression in the lungs. In the early treatment model, we investigated the role of nitric oxide synthase (NOS) inhibition with N(ω)-nitro-L-arginine methyl ester (L-NAME; 25 mg·kg(-1)·day(-1)) during ambrisentan treatment. In the early treatment model, ambrisentan improved survival with reduced lung fibrin and collagen III deposition, arterial medial wall thickness, and RVH. These changes were not affected by L-NAME administration. Ambrisentan did not reduce the influx of macrophages and neutrophils or prevent reduced irregular elastin expression. In the late treatment model, ambrisentan diminished PAH, RVH, and right ventricular peak pressure, demonstrating that RVH is reversible in the neonatal period. Alveolarization and vascularization were not affected by ambrisentan. In conclusion, ambrisentan prolongs survival and reduces lung injury, PAH, and RVH via a NOS-independent mechanism but does not affect inflammation and alveolar and vascular development in neonatal rats with CLD.

  19. Three-dimensional characterization of the vascular bed in bone metastasis of the rat by microcomputed tomography (MicroCT.

    Directory of Open Access Journals (Sweden)

    Hervé Nyangoga

    Full Text Available BACKGROUND: Angiogenesis contributes to proliferation and metastatic dissemination of cancer cells. Anatomy of blood vessels in tumors has been characterized with 2D techniques (histology or angiography. They are not fully representative of the trajectories of vessels throughout the tissues and are not adapted to analyze changes occurring inside the bone marrow cavities. METHODOLOGY/PRINCIPAL FINDINGS: We have characterized the vasculature of bone metastases in 3D at different times of evolution of the disease. Metastases were induced in the femur of Wistar rats by a local injection of Walker 256/B cells. Microfil®, (a silicone-based polymer was injected at euthanasia in the aorta 12, 19 and 26 days after injection of tumor cells. Undecalcified bones (containing the radio opaque vascular casts were analyzed by microCT, and a first 3D model was reconstructed. Bones were then decalcified and reanalyzed by microCT; a second model (comprising only the vessels was obtained and overimposed on the former, thus providing a clear visualization of vessel trajectories in the invaded metaphysic allowing quantitative evaluation of the vascular volume and vessel diameter. Histological analysis of the marrow was possible on the decalcified specimens. Walker 256/B cells induced a marked osteolysis with cortical perforations. The metaphysis of invaded bones became progressively hypervascular. New vessels replaced the major central medullar artery coming from the diaphyseal shaft. They sprouted from the periosteum and extended into the metastatic area. The newly formed vessels were irregular in diameter, tortuous with a disorganized architecture. A quantitative analysis of vascular volume indicated that neoangiogenesis increased with the development of the tumor with the appearance of vessels with a larger diameter. CONCLUSION: This new method evidenced the tumor angiogenesis in 3D at different development times of the metastasis growth. Bone and the vascular

  20. Effect of selective serotonin reuptake inhibitors on expression of 5-HT1AR and neurotransmitters in rats with vascular dementia.

    Science.gov (United States)

    Guo, K; Yin, G; Zi, X H; Zhu, H X; Pan, Q

    2016-12-02

    5-hydroxytryptamine receptor 1A (5-HT1AR) is closely associated with cognitive functions. Selective serotonin reuptake inhibitors (SSRIs) can protect individuals from brain damage following ischemia/hypoxia. To investigate the function of SSRIs in vascular dementia (VD), we established a rat model of VD, and observed the effect of SSRIs on the expression of 5-HT1AR mRNA and neurotransmitters. Male SD rats (6 months) were randomly assigned into sham, model, and SSRI groups (N = 30). VD was achieved by permanent ligation of the bilateral common carotid artery. Escitalopram, a highly selective 5-HT reabsorption inhibitor, was ip injected into the rats for three consecutive weeks. The Morris water-maze was used to test learning and memory. H&E staining for neuronal injury was conducted on cortical and hippocampal tissues. HPLC was used to determine the levels of dopamine (DA), 5-HT, and norepinephrine (NE). RT-PCR was used to determine expression of 5-HT1AR mRNA. As compared to control rats, model animals demonstrated elongated escape latency, lower platform crossing times, and significant injuries to hippocampal CA1 neurons. This was accompanied by reductions in DA, 5-HT, and NE levels in hippocampal tissues, as well as reduced cortical 5-HT and decreased 5-HT1AR mRNA expression (P < 0.05). Escitalopram treatments reduced escape latency, elevated platform crossing times, improved CA1 neuronal damage, increased DA and 5-HT levels in hippocampal and cortical neurons, as well as elevated expression of 5-HT1AR mRNA (P < 0.05). Therefore, SSRIs may improve cognitive dysfunction of VD rats, possibly by stimulating expression of neurotransmitters and protecting neurons.

  1. Gestational exposure to elevated testosterone levels induces hypertension via heightened vascular angiotensin II type 1 receptor signaling in rats.

    Science.gov (United States)

    Chinnathambi, Vijayakumar; More, Amar S; Hankins, Gary D; Yallampalli, Chandra; Sathishkumar, Kunju

    2014-07-01

    Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K(+) depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational

  2. [Double aortic arch: prenatal case report].

    Science.gov (United States)

    Budziszewska, Patrycja; Kuka, Dorota; Sodowski, Marcin; Sodowski, Krzysztof; Jeanty, Philippe; Skrzypulec, Violetta

    2009-09-01

    We have presented a case of prenatal double aortic arch, diagnosed by ultrasound, to demonstrate the importance of 3-vessel view by detecting aortic arch abnormalities. Double aortic arch is one the most common types of the vascular ring. The suspicion of a double aortic arch is raised by detecting the U-sign which is formed by the combination of both aortic arches and the left ductus arteriosus. In the 3-vessel view the ascending aorta and aortic arch are pointing to the right, whereas the left arch points to the left, and the trachea is seen between. The 4-chamber view appears normal, but the descending aorta is deviated medially. Literature review revealed an association between double aortic arch and congenital heart diseases in approximately 20% of cases; most often tetralogy of Fallot, transposition of great vessels, ventricular septal defects. Rarely there can be atresia of the segment of the aortic arch, which can be difficult to differentiate from other aortic arch anomalies associated with chromosomal abnormalities such as microdeletion of chromosome 22q11.

  3. Effects of in-vitro cultured calculus bovis on learning and memory impairments of hyperlipemia vascular dementia rats.

    Science.gov (United States)

    Zhong, Xiao-Ming; Ren, Xue-Cong; Lou, Ye-Liang; Chen, Meng-Jing; Li, Guan-Ze; Gong, Xue-Yuan; Huang, Zhen

    2016-11-04

    In-vitro cultured calculus bovis (ICCB) is a quality substitute for natural bezoar which is used for the therapeutic purpose of treating encephalopathy. ICCB has been authorized to use on clinic. The aim of the study is to evaluate the effects and the potential mechanisms of in-vitro cultured calculus bovis (ICCB) on learning and memory impairments of hyperlipemia vascular dementia (HVD) rats. The HVD model was established by permanent occlusion of bilateral common carotid arteries based on hyperlipemia rats. Learning and memory abilities were evaluated by morris water maze test and shuttle box test. Ultraviolet-visible spectrophotometry (UV-vis) was employed to determine the SOD, MDA and NO in cerebral tissue, as well as the TG in serum. HE staining and toluidine blue staining were employed to evaluate cone cells damage in hippocampus CA1. An immunohistochemistry was used to measure the Bax and Bcl-2 expressions in cerebral tissue. Compared with control group, the abilities of spatial learning and memory and conditional memory were decreased significantly in HVD group (Plearning and memory, elevated the SOD activity (Plearning and memory in HVD rats. It might be related to anti-oxidative, regulation of Bax and Bcl-2 expressions, and the alleviation of cone cells damage. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Genotype-Related Effect of Crowding Stress on Blood Pressure and Vascular Function in Young Female Rats

    Directory of Open Access Journals (Sweden)

    Peter Slezak

    2014-01-01

    Full Text Available This study investigated the influence of chronic crowding stress on nitric oxide (NO production, vascular function and oxidative status in young Wistar-Kyoto (WKY, borderline hypertensive (BHR and spontaneously hypertensive (SHR female rats. Five-week old rats were exposed to crowding for two weeks. Crowding elevated plasma corticosterone (P<0.05 and accelerated BP (P<0.01 versus basal only in BHR. NO production and superoxide concentration were significantly higher in the aortas of control BHR and SHR versus WKY. Total acetylcholine (ACh-induced relaxation in the femoral artery was reduced in control SHR versus WKY and BHR, and stress did not affect it significantly in any genotype. The attenuation of ACh-induced relaxation in SHR versus WKY was associated with reduction of its NO-independent component. Crowding elevated NO production in all strains investigated but superoxide concentration was increased only in WKY, which resulted in reduced NO-dependent relaxation in WKY. In crowded BHR and SHR, superoxide concentration was either unchanged or reduced, respectively, but NO-dependent relaxation was unchanged in both BHR and SHR versus their respective control group. This study points to genotype-related differences in stress vulnerability in young female rats. The most pronounced negative influence of stress was observed in BHR despite preserved endothelial function.

  5. Molecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase.

    OpenAIRE

    Nishida, K; Harrison, D.G.; Navas, J P; Fisher, A.A.; Dockery, S P; Uematsu, M; Nerem, R M; Alexander, R W; Murphy, T. J.

    1992-01-01

    The constitutive endothelial cell nitric oxide synthase (NOS) importantly regulates vascular homeostasis. To gain understanding of this enzyme, a pEF BOS cDNA library of 5 x 10(5) clones was prepared from bovine aortic endothelial cells (BAEC) and screened with a 2.8-kb cDNA BamHI fragment of rat brain NOS. Clone pBOS13 was found to express NO synthase activity when transfected into COS-7 cells. Sequence analysis revealed sequences compatible with binding domains for calcium/calmodulin, flavi...

  6. Achilles Tendon Vascularization of Proximal, Medial, and Distal Portion Before and After Partial Lesion in Rats Treated with Phototherapy.

    Science.gov (United States)

    Ferreira, Rafaela; Silva, Rosangela; Folha, Roberta A C; Polacow, Maria Luiza O; Teodori, Rosana Macher; Pinfildi, Carlos Eduardo

    2015-12-01

    The Achilles tendon is one of the tendons most commonly injured by microtraumas and overuse during sports practice. This tendon is especially fragile because of the low blood supply in its central part. Nevertheless, the literature does not offer enough scientific support to explain the composition and vascular dynamic of animal tendons, despite the relevance of being able to observe if the animal tendon undergoes the same processes of vascularization in different regions, as occurs in humans. We used 28 rats weighing 280 ± 20 g, which were divided into four groups with seven animals each (control, sham, 830 nm, 660 nm). The laser parameters were: power output 60 mW for both lasers, 40 J/cm(2) of energy density, total energy 1.1 J, power density 2.14 W/cm(2), and application time 18.6 sec. This study evaluated the vascular constitution of healthy and injured calcaneous tendons. The tendons of each animal were processed to be embedded in Paraplast and, after that, they were divided into three parts: proximal, medial, and distal. Afterwards, they were cut in slices of 6 μm were made, then they were stained with hematoxylin and eosin. Using an ocular lens reticulated with magnification × 400, we analyzed the number and the area density of the blood vessels using morphometric methods. Data were analyzed with the Shapiro-Wilk test, followed by Tukey, considering p as <0.05. The area density and the number of blood vessels in the proximal part were 36% and 42%, respectively, of the values found in the medial part. The distal part had 64% more vessels and 52.8% more area density (p < 0.05) than the medial part. Low-level laser therapy (LLLT) had no effect on the studied parameters. The vascularization of rat tendon is similar to that of humans, which contributes to the studies of therapies that have been applied in humans.

  7. An Interaction of the Pre- and Post-Weaning Diets Rich in Omega-6 Polyunsaturated Fats Alters Plasma Lipids, Hepatic Gene Expression and Aortic Vascular Reactivity in Adult 057Bl/6 Mice

    Directory of Open Access Journals (Sweden)

    Kanta Chechi

    2010-01-01

    Full Text Available Aim To investigate the effects of diets rich in n-6 polyunsaturated fats (PUFA fed during pre- and post-weaning time periods on the lipid metabolism and vascular reactivity in adult C57Bl/6 mice, in order to assess the impact of maternal nutrition and its interaction with the offspring diet on the metabolism of adult offspring. Methods Female C57Bl/6 mice were fed a high-fat diet enriched with n-6 PUFA (P or control diet (C for 2-weeks before, during mating, gestation and lactation, while their pups received either P or C for 8-weeks post-weaning. Results A significant interaction between the maternal and post-weaning diets was observed for the offspring body weight, food-, caloric-intake, plasma lipids, hepatic mRNA expression of lecithin cholesterol acyltransferase, aortic contractile and relaxation responses ( P < 0.05. Conclusion The overall metabolic and physiological outcome in the offspring is dependent upon the interaction between the pre- and post-weaning dietary environments.

  8. Neuroprotective effect of selective DPP-4 inhibitor in experimental vascular dementia.

    Science.gov (United States)

    Jain, Swati; Sharma, Bhupesh

    2015-12-01

    Vascular risk factors are associated with a higher incidence of dementia. Diabetes mellitus is considered as a main risk factor for Alzheimer's disease and vascular dementia. Both forms of dementia are posing greater risk to the world population and are increasing at a faster rate. In the past we have reported the induction of vascular dementia by experimental diabetes. This study investigates the role of vildagliptin, a dipeptidyl peptidase-4 inhibitor in the pharmacological interdiction of pancreatectomy diabetes induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. Pancreatectomy diabetes rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with increase in brain inflammation, oxidative stress and calcium. Administration of vildagliptin has significantly attenuated pancreatectomy induced impairment of learning, memory, endothelial function, blood brain barrier permeability and biochemical parameters. It may be concluded that vildagliptin, a dipeptidyl peptidase-4 inhibitor may be considered as potential pharmacological agents for the management of pancreatectomy induced endothelial dysfunction and subsequent vascular dementia. The selective modulators of dipeptidyl peptidase-4 may further be explored for their possible benefits in vascular dementia. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Increased cardiovascular risk in rats with primary renal dysfunction; mediating role for vascular endothelial function

    NARCIS (Netherlands)

    Szymanski, M. K.; Buikema, J. H.; van Veldhuisen, D. J.; Koster, J.; van der Velden, J.; Hamdani, N.; Hillege, J. L.; Schoemaker, R. G.

    Primary chronic kidney disease is associated with high cardiovascular risk. However, the exact mechanisms behind this cardiorenal interaction remain unclear. We investigated the interaction between heart and kidneys in novel animal model for cardiorenal interaction. Normal Wistar rats and Munich

  10. Impact of dietary nitrate supplementation via beetroot juice on exercising muscle vascular control in rats

    National Research Council Canada - National Science Library

    Ferguson, Scott K; Hirai, Daniel M; Copp, Steven W; Holdsworth, Clark T; Allen, Jason D; Jones, Andrew M; Musch, Timothy I; Poole, David C

    2013-01-01

    ...) within and among locomotory muscles during exercise is unknown. •  Inorganic NO 3 − supplementation with BR in rats resulted in lower exercising mean arterial pressure, lower blood [lactate...

  11. Metformin Exposure During Pregnancy and Lactation Did Not Cause Vascular Reactivity Alteration in Adult Male Offsprings.

    Science.gov (United States)

    Novi, Daniella R B S; Forcato, Simone; Vidigal, Camila B; Loiola, Guilherme H; Gerardin, Daniela C C; Ceravolo, Graziela S

    2017-11-01

    Metformin has been used for the treatment of some metabolic diseases during gestation and the beneficial effects of metformin to the vascular system have been described in diabetic and obese animal models. Nevertheless, the long-term consequences to the vascular system of offsprings maternally exposed to metformin have not yet been characterized. Therefore, we want to test the hypothesis that gestational and lactational exposure to metformin would be safe for the vascular reactivity of male adult offsprings. Wistar female rats were treated with metformin 293 mg·kg·d, by gavage, from gestational day (GD) 0 to GD 21 (METG) or GD 0 until postnatal day 21 (METGL). Control dams received water by gavage in the same periods (CTRG and CTRGL). In male offsprings (75 days), the aortic reactivity to phenylephrine, acetylcholine, and sodium nitroprusside in the presence or absence of endothelium were evaluated. The results demonstrated that aortic contraction and relaxation were similar between groups. These data showed that metformin exposure during pregnancy and lactation did not interfere with aortic reactivity, suggesting that metformin exposure during gestational and lactation are safe for the offsprings' vascular system.

  12. Activation of adenosine A2A receptors by polydeoxyribonucleotide increases vascular endothelial growth factor and protects against testicular damage induced by experimental varicocele in rats.

    Science.gov (United States)

    Minutoli, Letteria; Arena, Salvatore; Bonvissuto, Giulio; Bitto, Alessandra; Polito, Francesca; Irrera, Natasha; Arena, Francesco; Fragalà, Eugenia; Romeo, Carmelo; Nicotina, Piero Antonio; Fazzari, Carmine; Marini, Herbert; Implatini, Alessandra; Grimaldi, Silvia; Cantone, Noemi; Di Benedetto, Vincenzo; Squadrito, Francesco; Altavilla, Domenica; Morgia, Giuseppe

    2011-03-15

    In rat experimental varicocele, polydeoxyribonucleotide (PDRN) induces vascular endothelial growth factor (VEGF) production, thereby enhancing testicular function. This may point to a new therapeutic approach in human varicocele. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Puerarin up-regulates methyl-CpG binding protein 2 phosphorylation in hippocampus of vascular dementia rats.

    Science.gov (United States)

    Wang, Hu-Qing; Zhang, Meng; Zhao, Jia-Xin; Wu, Hai-Qin; Gao, Zhen; Zhang, Gui-Lian; Zhang, Ru

    2018-01-09

    To observe the effect of puerarin on methyl-CpG binding protein 2 (MeCP2) phosphorylation (pMeCP2) in the hippocampus of a rat model of vascular dementia (VD). Thirty-six healthy Sprague-Dawley rats were randomly assigned to the sham-operated group, dementia group and puerarintreated group using a random number table (n=12 per group). The modifified permanent bilateral common carotid artery occlusion method was used to establish the VD model. The sham-operated and dementia groups were given 2 mL/d of saline, while the puerarin-treated group was given 100 mg/(kg•d) of puerarin for 17 days. The learning and memory abilities were evaluated by the Morris water maze test. Hematoxylin-eosin staining, immunohistochemical (IHC) staining and Western blot analysis were carried out to observe changes in neuron morphology and in level of pMeCP2 in the hippocampus, respectively. The morphologies of rat hippocampal neurons in the puerarintreated group were markedly improved compared with the dementia group. The escape latency of the dementia group was significantly longer than the sham-operated group (Pplatform times of the dementia group were signifificantly decreased compared with the sham-operated group (P0.05). Western blot analysis showed no signifificant difference of MeCP2 expression among 3 groups (P>0.05). The expression of pMeCP2 in the dementia group was signifificantly increased compared with the sham-operated group, while it in the puerarin-treated group was signifificantly increased compared with the dementia group (Plearning and memory ablities in a rat model of VD.

  14. Assessment of enhanced endothelium-dependent vasodilation by intermittent fasting in Wistar albino rats.

    Science.gov (United States)

    Razzak, Rima L Abdul; Abu-Hozaifa, Bodour M; Bamosa, Abdullah O; Ali, Nemah M

    2011-01-01

    Intermittent fasting (IF), a type of feeding regimen where the frequency of eating is reduced enhances cardiovascular stress adaptation and improves cardiovascular risk factors in rats. Data on the effect of IF on the endothelium is not common, so we examined whether IF showed similarity to documented beneficial effects of caloric restriction on endothelium-dependent vasodilatory responses of rat aortic rings. 25 young male Wistar rats had ad libitum (AL) access to food and 25 others were provided with food every other day for 2 months, during which their weight was measured every 2 weeks. Vascular reactivity of abdominal aorta was simultaneously evaluated using dual wire myographs. Weight gain was greater in the AL group (P<0.001) at all weighing intervals. Acetylcholine (ACh; 10(-10)-10(-5)M) produced greater (P<0.05) vasorelaxation in IF rats at the two highest concentrations. IF reduces weight gain in young male rats and improves their aortic endothelium-dependent vasorelaxation.

  15. Local versus systemic influences on uterine vascular reactivity during pregnancy in the single-horn gravid rat.

    Science.gov (United States)

    Fuller, Robert; Colton, Ilsley; Gokina, Natalia; Mandala, Maurizio; Osol, George

    2011-08-01

    This study was conducted to determine whether gestational changes in maternal uterine artery reactivity are primarily driven by local vs. systemic factors. Rats underwent surgical ligation of one oviduct, thereby restricting implantation and pregnancy to one uterine horn while maintaining a gestational endocrine milieu. Uterine arcuate arteries were isolated and cannulated to evaluate reactivity. Vessels from the implanted horn were significantly more sensitive to phenylephrine and less sensitive to sodium nitroprusside than those from the non-implanted horn; endothelial basal calcium levels were only increased in the implanted horn. Conversely, there were no differences in sensitivity to acetylcholine, or its effects on endothelial cell calcium, although efficacy was greater in vessels from the implanted vs. non-implanted horn. These findings demonstrate that local factors are predominant in inducing changes in vascular smooth muscle function, while endothelial adaptations result from an interplay between local and systemic factors, with distinct effects attributable to each.

  16. Quantification of vascular endothelial growth factor and neuropilins mRNAs during rat brain maturation by real-time PCR.

    Science.gov (United States)

    Adris, Soraya; Ojeda, Elizabeth; Genero, Mario; Argibay, Pablo

    2005-09-01

    1. Vascular endothelial growth factor (VEGF) has been related with several brain functions such as angiogenesis, neuroprotection, and neurogenesis. 2. We studied the mRNA expression of the two most important isoforms of VEGF (VEGF120 and VEGF164) as well as one type of VEGF receptors, neuropilins (NRP), during maturation in the rat brain using real-time PCR. 3. Today, real-time PCR is the method of choice for rapid and reliable quantification of mRNA transcription. 4. VEGF120 has little changes in its expression between P5 and P30. 5. However, VEGF164 increased its expression 2-folds at P15 in comparison to P5, remaining at this level in the adult brain (P30). 6. Both types of NRP, NRP-1 and NRP-2, which only bind VEGF164, increased their expression about 2-folds only at P30, at levels similar to those observed for VEGF164.

  17. Vascular, but not luminal, activation of FFAR1 (GPR40) stimulates GLP-1 secretion from isolated perfused rat small intestine

    DEFF Research Database (Denmark)

    Christensen, Louise Wulff; Kuhre, Rune Ehrenreich; Janus, Charlotte

    2015-01-01

    - ined the effect of FFAR1 activation on GLP-1 secretion using isolated, per- fused small intestines from rats, a physiologically relevant model allowing distinction between direct and indirect effects of FFAR1 activation. The endogenous FFAR1 ligand, linoleic acid (LA), and four synthetic FFAR1 ago......- nists (TAK-875, AMG 837, AM-1638, and AM-5262) were administered through intraluminal and intra-arterial routes, respectively, and dynamic changes in GLP-1 secretion were evaluated. Vascular administration of 10 mol/L TAK-875, 10 mol/L AMG 837, 1 mol/L and 0.1 mol/L AM-1638, 1 mol/L AM-6252, and 1 mmol....../L LA, all significantly increased GLP-1 secretion compared to basal levels (Padministration of LA and FFAR1 agonists was ineffective. Thus, both natural and small-mole- cule agonists of the FFAR1 receptor appear to require absorption prior to stimulating GLP-1 secretion...

  18. Vascular matrix metalloproteinase-9 mediates the inhibition of myogenic reactivity in small arteries isolated from rats after short-term administration of relaxin.

    Science.gov (United States)

    Jeyabalan, Arundhathi; Novak, Jacqueline; Doty, Ketah D; Matthews, Julianna; Fisher, Michelle C; Kerchner, Laurie J; Conrad, Kirk P

    2007-01-01

    During pregnancy and chronic relaxin administration to nonpregnant rats (for days), vascular MMP (matrix metalloproteinase)-2 is increased and mediates renal vasodilation, hyperfiltration, and inhibition of myogenic reactivity of small renal arteries. However, the renal vasodilatory actions of relaxin also occur after only several hours of hormone administration to nonpregnant rats, and we hypothesized a pivotal role for vascular MMP-2. Accordingly, we used gelatin zymography, which reveals not only vascular MMP-2, but also MMP-9 activity in small renal arteries isolated from rats administered recombinant human relaxin (rhRLX) or vehicle for 4-6 h. Furthermore, we tested whether myogenic reactivity is inhibited, and if so, whether the inhibition is mediated by increased vascular MMP-2. Surprisingly, we detected no significant difference in either pro or active MMP-2 in small renal arteries isolated from rhRLX and vehicle control treatment groups. In contrast, vascular MMP-9 was up-regulated by 70% (P vascular smooth muscle. MMP-9, but not MMP-2 activity, was also increased in mesenteric arteries after short-term rhRLX administration (P 0.05 vs. vehicle, respectively). Myogenic reactivity was inhibited in small renal arteries isolated from nonpregnant rats treated with rhRLX for 4-6 h (P < 0.01 vs. vehicle) and was completely restored by incubation with MMP-9, but not MMP-2 neutralizing antibodies in vitro. In contrast to chronic rhRLX administration, MMP-9 rather than MMP-2 plays a central role in the vasodilatory effect of short-term relaxin administration.

  19. Deferoxamine Improves Alveolar and Pulmonary Vascular Development by Upregulating Hypoxia-inducible Factor-1α in a Rat Model of Bronchopulmonary Dysplasia.

    Science.gov (United States)

    Choi, Chang Won; Lee, Juyoung; Lee, Hyun Ju; Park, Hyoung-Sook; Chun, Yang-Sook; Kim, Beyong Il

    2015-09-01

    Fetal lung development normally occurs in a hypoxic environment. Hypoxia-inducible factor (HIF)-1α is robustly induced under hypoxia and transactivates many genes that are essential for fetal development. Most preterm infants are prematurely exposed to hyperoxia, which can halt hypoxia-driven lung maturation. We were to investigate whether the HIF-1α inducer, deferoxamine (DFX) can improve alveolarization in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was produced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85% for 7 days), and DFX (150 mg/kg/d) or vehicle was administered to rat pups intraperitoneally for 14 days. On day 14, the rat pups were sacrificed and their lungs were removed and examined. A parallel in vitro study was performed with a human small airway epithelial cell line to test whether DFX induces the expression of HIF-1α and its target genes. Alveolarization and pulmonary vascular development were impaired in rats with BPD. However, DFX significantly ameliorated these effects. Immunohistochemical analysis showed that HIF-1α was significantly upregulated in the lungs of BPD rats treated with DFX. DFX was also found to induce HIF-1α in human small airway epithelial cells and to promote the expression of HIF-1α target genes. Our data suggest that DFX induces and activates HIF-1α, thereby improving alveolarization and vascular distribution in the lungs of rats with BPD.

  20. Effect of losartan with folic acid on plasma homocysteine and vascular ultrastructural changes in spontaneously hypertensive rats.

    Science.gov (United States)

    Zhu, Lihe; Yu, Jiong; Jia, Baofu; Zhao, Feng; Tang, Mengmeng; Hu, Lufeng; Lin, Feiyan

    2015-01-01

    Elevated homocysteine (Hcy) is a high risk factor of hypertension due to its function in endothelial dysfunction. Its level in the blood is strongly influenced by folic acid. In order to investigate the effects of losartan with folic acid on plasma level of Hcy and vascular ultrastructural changes, thirty spontaneously hypertensive rats (SHR) involved and randomly divided into three groups (n=10): SHR-C group (control), SHR-L group (losartan 25 mg · kg(-1) · d(-1)), SHR-L+Y group (losartan 25 mg · kg(-1) · d(-1) + folic acid 0.4 mg · kg(-1) · d(-1)). Another 10 Wistar Rats involved as WKY-C group for normal control. The level of plasma Hcy was measured dynamically by LS-MS, the vascular ultrastructural changes were analyzed by light and electron microscopy. Moreover, the thickness and area of aorta was measured. The results showed the Hcy levels in four groups were WKY-C 7.49 ± 1.95 μmol/L; SHR-C 8.45 ± 1.90 μmol/L; SHR-L 8.28 ± 2.11 μmol/L; SHR-L+Y 7.53 ± 2.02 μmol/L at 80 days. There was no significant change for plasma Hcy (P>0.05). The morphological change showed the subendothelial space didn't increased significantly, the endothelial cells have a more smooth and intact cellular membrane in SHR-L+Y group. In conclusion, Losartan combined with folic acid could improve arterial endothelial structure in SHR which has no significant correlation with plasma Hcy.

  1. Curcumol Promotes Vascular Endothelial Growth Factor (VEGF)-Mediated Diabetic Wound Healing in Streptozotocin-Induced Hyperglycemic Rats.

    Science.gov (United States)

    Zhou, Jie; Ni, Maowei; Liu, Xia; Ren, Zeming; Zheng, Zhiguo

    2017-01-31

    BACKGROUND Wound healing in chronic diabetic mellitus is mainly associated with the management of angiogenesis. The angiogenic mechanism of vascular endothelial growth factor (VEGF) has been widely studied in the context of diabetic ulcers. The aim of this study was to investigate the wound-healing potential of curcumol in streptozotocin-induced diabetic rats. MATERIAL AND METHODS Sixty male SD (Sprague Dawley) rats were purchased and randomly assigned into four groups: a control group and a model group treated with blank ointment, a high-dose curcumol group, and a low-dose curcumol group. The number of animals in each group was 15. Diabetes was induced by an intraperitoneal injection of streptozotocin. Two cutaneous wounds were incised at the dorsal region of all the experimental animals. Wound healing was assessed for all animal groups by observing the rate of wound closure. The expression of VEGF at the wound sites was studied by immunohistochemical staining to evaluate the vascular endothelial cell reaction. VEGF protein and related mRNA levels were analyzed by Western blotting and RT-PCR (reverse transcription-polymerase chain reaction). RESULTS Curcumol treatment significantly increased the rates of wound closure in treated animals, and hence wound healing was drastically enhanced for treatment groups compared to control groups. Histological observations and related mRNA and protein levels showed a higher VEGF expression in the treatment groups. CONCLUSIONS Our analyses clearly suggested that the observed enhancement in wound healing as a result of curcumol administration was attributable to VEGF-mediated angiogenesis.

  2. [Recombinant AAV1 mediated vascular endothelial growth factor gene expression promotes angiogenesis and improves neural function: experiment with rats].

    Science.gov (United States)

    Li, Shi-fang; Meng, Qing-hai; Yao, Wei-cheng; Hu, Guo-jie; Li, Gui-lin; Li, Zhao-jian; Wei, Jun-ji; Bo, Yong-li; Zhang, Zi-heng; Wang, Ren-zhi

    2009-01-20

    To investigate the therapeutic effect of vascular endothelial growth factor (VEGF) gene expression mediated by recombinant AAV1 (rAAV1) vector in brain ischemia and the mechanism thereof. Sixty-four SD rats were randomly divided into 2 equal groups and received intra-ventricular injection with rAAV1-VEGF or rAAV1-lacZ as controls. 21 days later the rats underwent transient middle cerebral artery occlusion (MCAO). Neurological severity score (NSS) was recorded 1, 2, 3, 7, 14, and 21 days after MCAO. 48 rats were sacrificed 21 days after MCAO and brains were taken out from 48 rats. Immune quantitative analysis was used to identify the quantity of VEGF expression. Immunohistochemistry was used to identify the site of VEGF expression. Immunofluorescence double labeling of von Willebrand factor (vWF) and 5-bromodeoxy-uridine (BrdU) was performed to detect the proliferation of endothelial cells. Fluorescein isothiocyanate (FITC)-dextran was infused into the caudal vein of 8 rats from each group and then the rats were killed with their brains taken out to evaluate the cerebral microvessel perfusion and microvessel density. The NSSs of the VEGF group 7, 14, and 21 days after MCAO were all significantly lower than those of the control group (all P < 0.05), and the VEGF165 protein expression quantity was 27 times as that of the control group (P < 0.05). Immunohistochemistry demonstrated that VEGF expression was distributed mainly in the caudate putamen, corpus callosum, choroid plexus, and hippocampus in the VEGF group, while no expression was detected in the control group. The microvessel density of the VEGF group was 157 +/- 13, significantly higher than that of the control group [(89 +/- 9), P < 0.05]. BrdU +/vWF + endothelial cells were detected in the area adjacent to the MCAO. The density of microvessel infused with FITC-dextran was (152,617 +/- 13,076) microm2/mm2 in the VEGF group, significantly higher than that of the control group [(91,658 +/- 6577) microm2/mm2 P

  3. Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure

    Directory of Open Access Journals (Sweden)

    Olivier Phan

    2015-01-01

    Full Text Available Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23 levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21, a new iron-based phosphate binder, versus lanthanum carbonate (La and sevelamer carbonate (Se, on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

  4. The vascular response to photodynamic therapy with ATX-S10Na(II) in the normal rat colon.

    Science.gov (United States)

    Harada, Masahiko; Woodhams, Josephine; MacRobert, Alexander J; Feneley, Mark R; Kato, Harubumi; Bown, Stephen G

    2005-06-01

    The mechanism of tissue damage from photodynamic therapy (PDT) may be cellular, vascular or both, depending on the photosensitising agent and the treatment conditions. Well established photosensitisers like porfimer sodium have an optimum drug light interval of two days and may cause skin photosensitivity lasting several weeks. ATX-S10Na(II) is a new photosensitiser that remains largely in the vasculature after systemic administration and clears from the body within a few hours. The present study looks at the factors controlling the extent of PDT necrosis using ATX-S10Na(II) and correlates these with changes in the circulation after PDT. Normal Wistar rats were sensitised with ATX-S10Na(II), 2 mg/kg. At laparotomy, a laser fibre was positioned just touching the colonic mucosa and 50 J light at 670 nm delivered varying the drug light interval (0.5-24 h) and light delivery regime (100 mW continuous, 20 mW continuous or 100 mW in five fractions). Some animals were killed at three days to document the area of necrosis, others received fluorescein shortly prior to death (from a few minutes to three days after PDT) to outline the zone of PDT induced vascular shutdown. Maximum necrosis was seen with the shortest drug light interval (0.5 h), with no effect by 6 h. Fractionating the light or lowering the power did not increase the necrosis. The area of fluorescein exclusion increased over the first 2 h after PDT (in contrast to the re-perfusion seen with other photosensitisers) and correlated with the area of necrosis. PDT with ATX-S10Na(II) is most effective with a drug light interval of less than one hour. It induces irreversible vascular shutdown that extends after completion of light delivery and which is largely independent of the light delivery regime.

  5. Carbon monoxide does not contribute to vascular tonus improvement in exercise-trained rats with chronic nitric oxide synthase inhibition.

    Science.gov (United States)

    Ülker, Seher Nasırcılar; Koçer, Günnur; Şentürk, Ümit Kemal

    2017-05-01

    Carbon monoxide (CO), an end product of heme oxygenase (HO) that is involved in the regulation of vascular tonus, may show a compensatory effect in nitric oxide (NO) deficiency. This study aimed to assess the effect of the HO/CO system on the vascular tone in exercise-trained rats with hypertension induced by chronic NO synthase (NOS) inhibition. Hypertension was induced by N-nitro-l-arginine methyl ester (25 mg/kg/day in drinking water), and exercise training comprised swimming 1 h/day, 5 days/week, for 6 weeks. Systolic blood pressure (BP) was measured weekly using a tail-cuff method. The effects of hypertension and/or exercise-training on the constriction and relaxation responses of the thoracic aorta and resistance arteries of the mesenteric and gastrocnemius vascular beds were evaluated. NOS inhibition produced a gradually developed hypertension, and the magnitude of the increase in BP was significantly attenuated by exercise training. Although phenylephrine (Phe)-induced contraction responses of aorta incubated with an HO-1 inhibitor were reduced in hypertensive animals, there was no difference in the hypertensive-exercise group. However, thoracic aortas in the hypertensive-exercise group exhibited significantly more relaxation in response to a CO donor. There was no change in Phe-induced contraction with or without HO inhibition CO donor relaxation responses in both resistance arteries. These results suggest that the HO/CO system does not contribute to diminishing BP by exercise training in a NOS inhibition-induced hypertension model. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Proteomic analysis reveals that proteasome subunit beta 6 is involved in hypoxia-induced pulmonary vascular remodeling in rats.

    Directory of Open Access Journals (Sweden)

    Jian Wang

    Full Text Available Chronic hypoxia (CH is known to be one of the major causes of pulmonary hypertension (PH, which is characterized by sustained elevation of pulmonary vascular resistance resulting from vascular remodeling. In this study, we investigated whether the ubiquitin proteasome system (UPS was involved in the mechanism of hypoxia-induced pulmonary vascular remodeling. We isolated the distal pulmonary artery (PA from a previously defined chronic hypoxic pulmonary hypertension (CHPH rat model, performed proteomic analyses in search of differentially expressed proteins belonging to the UPS, and subsequently identified their roles in arterial remodeling.Twenty-two proteins were differently expressed between the CH and normoxic group. Among them, the expression of proteasome subunit beta (PSMB 1 and PSMB6 increased after CH exposure. Given that PSMB1 is a well-known structural subunit and PSMB6 is a functional subunit, we sought to assess whether PSMB6 could be related to the multiple functional changes during the CHPH process. We confirmed the proteomic results by real-time PCR and Western blot. With the increase in quantity of the active subunit, proteasome activity in both cultured pulmonary artery smooth muscle cells (PASMCs and isolated PA from the hypoxic group increased. An MTT assay revealed that the proteasome inhibitor MG132 was able to attenuate the hypoxia-induced proliferation of PASMC in a dose-dependent manner. Knockdown of PSMB6 using siRNA also prevented hypoxia-induced proliferation.The present study revealed the association between increased PSMB6 and CHPH. CH up-regulated proteasome activity and the proliferation of PASMCs, which may have been related to increased PSMB6 expression and the subsequently enhanced functional catalytic sites of the proteasome. These results suggested an essential role of the proteasome during CHPH development, a novel finding requiring further study.

  7. Vascular changes in rat hippocampus following a high saturated fat and cholesterol diet.

    Science.gov (United States)

    Freeman, Linnea R; Granholm, Ann-Charlotte E

    2012-04-01

    The long-term effects of a diet rich in saturated fat and cholesterol on the hippocampus were evaluated in this study. It has previously been shown that this type of diet is detrimental to health, particularly affecting peripheral organs such as the heart and liver. However, effects on the brain have not been fully evaluated. This study focused on the hippocampus, a brain region instrumental for learning and memory and vulnerable to ischemic damage. Reduced blood-brain barrier (BBB) integrity and increased microgliosis were observed in the hippocampus of rats fed a high-saturated-fat and cholesterol (HFHC) diet for 6 months. Interestingly, an increase in hippocampal protein levels of occludin, a tight junction protein, was found in HFHC-treated rats as well. Further investigation revealed decreased expression of the occludin protein in blood vessels and increased expression in the dentate gyrus hilar neurons and mossy fibers of the hippocampal cornus ammonis 3 in HFHC-treated rats. Our results show alterations in BBB integrity and expression of tight junction proteins after long-term exposure to HFHC diet in rats. These findings may suggest a biologic mechanism for previously observed behavioral deficits occurring in rats fed this diet.

  8. Effect of Cymbopogon citratus and Citral on Vascular Smooth Muscle of the Isolated Thoracic Rat Aorta

    OpenAIRE

    Devi, R. Chitra; Sim, S. M.; Ismail, R.

    2012-01-01

    Cymbopogon citratus has been shown to have antioxidant, antimicrobial, antispasmodic and chemo-protective properties. Citral, is the major constituent of C. citratus. This study investigated the effects of methanolic extracts of leaves (LE), stems (SE), and roots (RE) of C. citratus and citral on vascular smooth muscle and explored their possible mechanisms of action. The experiment was conducted using isolated tissue preparations, where citral, LE, SE, and RE were added separately into a tis...

  9. Presence and vascular pharmacology of KATP channel subtypes in rat central and peripheral tissues

    DEFF Research Database (Denmark)

    Ploug, Kenneth Beri; Baun, Michael; Hay-Schmidt, Anders

    2010-01-01

    -inducing effects of K(ATP) channel openers and that a Kir6.1/SUR2B specific blocker might be effective in the treatment of primary headaches such as migraine. Since K(ATP) channels are ubiquitous, we characterized the K(ATP) channel subtypes in major rat cranial and peripheral arteries and organs in order...... to understand the possible adverse effects of a Kir6.1/SUR2B blocker. We studied the mRNA expression of K(ATP) channel subunits in rat femoral, mesenteric, renal, coronary, basilar, middle cerebral and middle meningeal arteries and in tissue from rat heart, brain, liver, colon, lung, kidney and pancreas. We...

  10. Diagnosis, imaging and clinical management of aortic coarctation

    NARCIS (Netherlands)

    Dijkema, Elles J; Leiner, Tim|info:eu-repo/dai/nl/238322467; Grotenhuis, Heynric B|info:eu-repo/dai/nl/32203034X

    2017-01-01

    Coarctation of the aorta (CoA) is a well-known congenital heart disease (CHD), which is often associated with several other cardiac and vascular anomalies, such as bicuspid aortic valve (BAV), ventricular septal defect, patent ductus arteriosus and aortic arch hypoplasia. Despite echocardiographic

  11. Nitrate decreases xanthine oxidoreductase-mediated nitrite reductase activity and attenuates vascular and blood pressure responses to nitrite

    Directory of Open Access Journals (Sweden)

    Célio Damacena-Angelis

    2017-08-01

    Full Text Available Nitrite and nitrate restore deficient endogenous nitric oxide (NO production as they are converted back to NO, and therefore complement the classic enzymatic NO synthesis. Circulating nitrate and nitrite must cross membrane barriers to produce their effects and increased nitrate concentrations may attenuate the nitrite influx into cells, decreasing NO generation from nitrite. Moreover, xanthine oxidoreductase (XOR mediates NO formation from nitrite and nitrate. However, no study has examined whether nitrate attenuates XOR-mediated NO generation from nitrite. We hypothesized that nitrate attenuates the vascular and blood pressure responses to nitrite either by interfering with nitrite influx into vascular tissue, or by competing with nitrite for XOR, thus inhibiting XOR-mediated NO generation. We used two independent vascular function assays in rats (aortic ring preparations and isolated mesenteric arterial bed perfusion to examine the effects of sodium nitrate on the concentration-dependent responses to sodium nitrite. Both assays showed that nitrate attenuated the vascular responses to nitrite. Conversely, the aortic responses to the NO donor DETANONOate were not affected by sodium nitrate. Further confirming these results, we found that nitrate attenuated the acute blood pressure lowering effects of increasing doses of nitrite infused intravenously in freely moving rats. The possibility that nitrate could compete with nitrite and decrease nitrite influx into cells was tested by measuring the accumulation of nitrogen-15-labeled nitrite (15N-nitrite by aortic rings using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS. Nitrate exerted no effect on aortic accumulation of 15N-nitrite. Next, we used chemiluminescence-based NO detection to examine whether nitrate attenuates XOR-mediated nitrite reductase activity. Nitrate significantly shifted the Michaelis Menten saturation curve to the right, with a 3-fold increase in

  12. Green synthesis of silver nanoparticles using Achillea biebersteinii flower extract and its anti-angiogenic properties in the rat aortic ring model.

    Science.gov (United States)

    Baharara, Javad; Namvar, Farideh; Ramezani, Tayebe; Hosseini, Nasrin; Mohamad, Rosfarizan

    2014-04-15

    Silver nanoparticles display unique physical and biological properties which have attracted intensive research interest because of their important medical applications. In this study silver nanoparticles (Ab.Ag-NPs) were synthesized for biomedical applications using a completely green biosynthetic method using Achillea biebersteinii flowers extract. The structure and properties of Ab.Ag-NPs were investigated using UV-visible spectroscopic techniques, transmission electron microscopy (TEM), zeta potential and energy dispersive X-ray spectrometers (EDS). The UV-visible spectroscopic analysis showed the absorbance peak at 460 nm, which indicates the synthesis of silver nanoparticles. The average particle diameter as determined by TEM was found to be 12±2 nm. The zeta potential analysis indicated that Ab.Ag-NPs have good stability EDX analysis also exhibits presentation of silver element. As angiogenesis is an important phenomenon and as growth factors imbalance in this process causes the acceleration of several diseases including cancer, the anti-angiogenic properties of Ab.Ag-NPs were evaluated using the rat aortic ring model. The results showed that Ab.Ag-NPs (200 μg/mL) lead to a 50% reduction in the length and number of vessel-like structures. The synthesized silver nanoparticles from the Achillea biebersteinii flowers extract, which do not involve any harmful chemicals were well-dispersed and stabilized through this green method and showed potential therapeutic benefits against angiogenesis.

  13. Green Synthesis of Silver Nanoparticles using Achillea biebersteinii Flower Extract and Its Anti-Angiogenic Properties in the Rat Aortic Ring Model

    Directory of Open Access Journals (Sweden)

    Javad Baharara

    2014-04-01

    Full Text Available Silver nanoparticles display unique physical and biological properties which have attracted intensive research interest because of their important medical applications. In this study silver nanoparticles (Ab.Ag-NPs were synthesized for biomedical applications using a completely green biosynthetic method using Achillea biebersteinii flowers extract. The structure and properties of Ab.Ag-NPs were investigated using UV-visible spectroscopic techniques, transmission electron microscopy (TEM, zeta potential and energy dispersive X-ray spectrometers (EDS. The UV-visible spectroscopic analysis showed the absorbance peak at 460 nm, which indicates the synthesis of silver nanoparticles. The average particle diameter as determined by TEM was found to be 12 ± 2 nm. The zeta potential analysis indicated that Ab.Ag-NPs have good stability EDX analysis also exhibits presentation of silver element. As angiogenesis is an important phenomenon and as growth factors imbalance in this process causes the acceleration of several diseases including cancer, the anti-angiogenic properties of Ab.Ag-NPs were evaluated using the rat aortic ring model. The results showed that Ab.Ag-NPs (200 μg/mL lead to a 50% reduction in the length and number of vessel-like structures. The synthesized silver nanoparticles from the Achillea biebersteinii flowers extract, which do not involve any harmful chemicals were well-dispersed and stabilized through this green method and showed potential therapeutic benefits against angiogenesis.

  14. Trimetazidine attenuates pressure overload-induced early cardiac energy dysfunction via regulation of neuropeptide Y system in a rat model of abdominal aortic constriction.

    Science.gov (United States)

    Chen, Ailan; Li, Wanglin; Chen, Xinyu; Shen, Yuechun; Dai, Wenjun; Dong, Qi; Li, Xinchun; Ou, Caiwen; Chen, Minsheng

    2016-11-17

    Metabolism remodeling has been recognized as an early event following cardiac pressure overload. However, its temporal association with ventricular hypertrophy has not been confirmed. Moreover, whether trimetazidine could favorably affect this process also needs to be determined. The aim of the study was to explore the temporal changes of myocardial metabolism remodeling following pressure-overload induced ventricular hypertrophy and the potential favorable effect of trimetazidine on myocardial metabolism remodeling. A rat model of abdominal aortic constriction (AAC)-induced cardiac pressure overload was induced. These rats were grouped as the AAC (no treatment) or TMZ group according to whether oral trimetazidine (TMZ, 40 mg/kg/d, for 5 days) was administered. Changes in cardiac structures were sequentially evaluated via echocardiography. The myocardial ADP/ATP ratio was determined to reflect the metabolic status, and changes in serum neuropeptide Y systems were evaluated. Myocardial metabolic disorder was acutely induced as evidenced by an increased ADP/ATP ratio within 7 days of AAC before the morphological changes in the myocardium, accompanied by up-regulation of serum oxidative stress markers and expression of fetal genes related to hypertrophy. Moreover, the serum NPY and myocardial NPY-1R, 2R, and 5R levels were increased within the acute phase of AAC-induced cardiac pressure overload. Pretreatment with TMZ could partly attenuate myocardial energy metabolic homeostasis, decrease serum levels of oxidative stress markers, attenuate the induction of hypertrophy-related myocardial fetal genes, inhibit the up-regulation of serum NPY levels, and further increase the myocardial expression of NPY receptors. Cardiac metabolic remodeling is an early change in the myocardium before the presence of typical morphological ventricular remodeling following cardiac pressure overload, and pretreatment with TMZ may at least partly reverse the acute metabolic disturbance

  15. Reactive Oxygen Species-Induced Impairment of Endothelium-Dependent Relaxations in Rat Aortic Rings: Protection by Methanolic Extracts of Phoebe grandis

    Directory of Open Access Journals (Sweden)

    Mohd Rais Mustafa

    2011-04-01

    Full Text Available Generation of reactive oxygen species plays a pivotal role in the development of cardiovascular diseases. The present study describes the effects of the methanolic extract of Phoebe grandis (MPG stem bark on reactive oxygen species-induced endothelial dysfunction in vitro. Endothelium-dependent (acetylcholine, ACh and -independent relaxation (sodium nitroprusside, SNP was investigated from isolated rat aorta of Sprague-Dawley (SD in the presence of the β-NADH (enzymatic superoxide inducer and MPG extract. Superoxide anion production in aortic vessels was measured by lucigen chemiluminesence. Thirty minutes incubation of the rat aorta in vitro with β-NADH increased superoxide radical production and significantly inhibited ACh-induced relaxations. Pretreatment with MPG (0.5, 5 and 50 μg/mL restored the ACh-induced relaxations (Rmax: 92.29% ± 2.93, 91.02% ± 4.54 and 88.31 ± 2.36, respectively in the presence of β-NADH. MPG was ineffective in reversing the impaired ACh-induced relaxations caused by pyrogallol, a non-enzymatic superoxide generator. Superoxide dismutase (a superoxide scavenger, however, reversed the impaired ACh relaxations induced by both β-NADH and pyrogallol. MPG also markedly inhibited the β-NADH-induced generation of the superoxide radicals. Furthermore, MPG scavenging peroxyl radicals generated by tBuOOH (10−4 M.These results indicate that MPG may improve the endothelium dependent relaxations to ACh through its scavenging activity as well as by inhibiting the NADH/NADPH oxidase induced generation of superoxide anions.

  16. Reactive oxygen species-induced impairment of endothelium-dependent relaxations in rat aortic rings: protection by methanolic extracts of Phoebe grandis.

    Science.gov (United States)

    Yeh-Siang, Lau; Subramaniam, Gopal; Hadi, A Hamid A; Murugan, Dharmani; Mustafa, Mohd Rais

    2011-04-06

    Generation of reactive oxygen species plays a pivotal role in the development of cardiovascular diseases. The present study describes the effects of the methanolic extract of Phoebe grandis (MPG) stem bark on reactive oxygen species-induced endothelial dysfunction in vitro. Endothelium-dependent (acetylcholine, ACh) and -independent relaxation (sodium nitroprusside, SNP) was investigated from isolated rat aorta of Sprague-Dawley (SD) in the presence of the β-NADH (enzymatic superoxide inducer) and MPG extract. Superoxide anion production in aortic vessels was measured by lucigen chemiluminesence. Thirty minutes incubation of the rat aorta in vitro with β-NADH increased superoxide radical production and significantly inhibited ACh-induced relaxations. Pretreatment with MPG (0.5, 5 and 50 μg/mL) restored the ACh-induced relaxations (R(max): 92.29% ± 2.93, 91.02% ± 4.54 and 88.31 ± 2.36, respectively) in the presence of β-NADH. MPG was ineffective in reversing the impaired ACh-induced relaxations caused by pyrogallol, a non-enzymatic superoxide generator. Superoxide dismutase (a superoxide scavenger), however, reversed the impaired ACh relaxations induced by both β-NADH and pyrogallol. MPG also markedly inhibited the β-NADH-induced generation of the superoxide radicals. Furthermore, MPG scavenging peroxyl radicals generated by tBuOOH (10⁻⁴ M).These results indicate that MPG may improve the endothelium dependent relaxations to ACh through its scavenging activity as well as by inhibiting the NADH/NADPH oxidase induced generation of superoxide anions.

  17. Melatonin Attenuates Aortic Endothelial Permeability and Arteriosclerosis in Streptozotocin-Induced Diabetic Rats: Possible Role of MLCK- and MLCP-Dependent MLC Phosphorylation.

    Science.gov (United States)

    Tang, Song-tao; Su, Huan; Zhang, Qiu; Tang, Hai-qin; Wang, Chang-jiang; Zhou, Qing; Wei, Wei; Zhu, Hua-qing; Wang, Yuan

    2016-01-01

    The development of diabetic macrovascular complications is a multifactorial process, and melatonin may possess cardiovascular protective properties. This study was designed to evaluate whether melatonin attenuates arteriosclerosis and endothelial permeability by suppressing the myosin light-chain kinase (MLCK)/myosin light-chain phosphorylation (p-MLC) system via the mitogen-activated protein kinase (MAPK) signaling pathway or by suppressing the myosin phosphatase-targeting subunit phosphorylation (p-MYPT)/p-MLC system in diabetes mellitus (DM). Rats were randomly divided into 4 groups, including control, high-fat diet, DM, and DM + melatonin groups. Melatonin was administered (10 mg/kg/d) by gavage for 12 weeks. The DM significantly increased the serum fasting blood glucose and lipid levels, as well as insulin resistance and endothelial dysfunction, which were attenuated by melatonin therapy to various extents. Importantly, the aortic endothelial permeability was significantly increased in DM rats but was dramatically reversed following treatment with melatonin. Our findings further indicated that hyperglycemia and hyperlipidemia enhanced the expressions of MLCK, p-MYPT, and p-MLC, which were partly associated with decreased membrane type 1 expression, increased extracellular signal-regulated kinase (ERK) phosphorylation, and increased p38 expression. However, these changes in protein expression were also significantly reversed by melatonin. Thus, our results are the first to demonstrate that the endothelial hyperpermeability induced by DM is associated with increased expressions of MLCK, p-MYPT, and p-MLC, which can be attenuated by melatonin at least partly through the ERK/p38 signaling pathway. © The Author(s) 2015.

  18. Six years' experience with prostaglandin I2 infusion in elective open repair of abdominal aortic aneurysm: a parallel group observational study in a tertiary referral vascular center.

    LENUS (Irish Health Repository)

    Beirne, Chris

    2008-11-01

    The prostaglandin I(2) (PGI(2)) analogue iloprost, a potent vasodilator and inhibitor of platelet activation, has traditionally been utilized in pulmonary hypertension and off-label use for revascularization of chronic critical lower limb ischemia. This study was designed to assess the effect of 72 hr iloprost infusion on systemic ischemia post-open elective abdominal aortic aneurysm (EAAA) surgery. Between January 2000 and 2007, 104 patients undergoing open EAAA were identified: 36 had juxtarenal, 15 had suprarenal, and 53 had infrarenal aneurysms, with a mean maximal diameter of 6.9 cm. The male-to-female ratio was 2.5:1, with a mean age of 71.9 years. No statistically significant difference was seen between the study groups with regard to age, sex, risk factors, American Society of Anesthesiologists (ASA) grade, or diameter of aneurysm repaired. All emergency, urgent, and endovascular procedures for aneurysms were excluded. Fifty-seven patients received iloprost infusion for 72 hr in the immediate postoperative period compared with 47 patients who did not. Patients were monitored for signs of pulmonary, renal, cardiac, systemic ischemia, and postoperative intensive care unit (ICU) morbidity. Statistically significantly increased ventilation rates (p=0.0048), pulmonary complication rates (p=0.0019), and myocardial ischemia (p=0.0446) were noted in those patients not receiving iloprost. These patients also had significantly higher renal indices including estimate glomerular filtration rate changes (p=0.041) and postoperative urea level rises (p=0.0286). Peripheral limb trashing was noted in five patients (11.6%) in the non-iloprost group compared with no patients who received iloprost. Increased rates of transfusion requirements and bowel complications were noted in those who did not receive iloprost, with their ICU stay greater than twice that of iloprost patients. All-cause morbidity affected 67% of patients not receiving iloprost compared to 40% who did

  19. Total vascular exclusion safely facilitates liver specific gene transfer by the HVJ (sendai virus)-liposome method in rats.

    Science.gov (United States)

    Kawashita, Yujo; Fujioka, Hikaru; Ohtsuru, Akira; Kuroda, Hiroaki; Eguchi, Susumu; Kaneda, Yasufumi; Yamashita, Shunichi; Kanematsu, Takashi

    2006-05-01

    Most virus mediated transfection systems are efficient; however, their highly immunogenic properties do tend to cause clinical problems. HVJ-liposome vector is a hybrid vector consisting of liposome and inactivated sendai virus (hemagglutinating virus of Japan HVJ), which has been reported to be have a low immunogenicity, while it can also be repeatedly administered. To enhance the transfection efficiency, especially in the liver, we investigated the efficacy of total vascular exclusion (TVE) during the portal vein injection (PVI) of the vectors. beta-galactosidase and luciferase expression were used as reporter genes. Wistar rats were injected with HVJ-liposome through PVI without TVE (PVI group, n = 10) or PVI with TVE (PVI + TVE group, n = 10). The control rats were infused with equal volumes of saline through the portal vein (control group n = 12). The transfection efficiencies were assessed by beta-galactosidase staining and a luciferase assay. Biochemical and histological analyses were performed to evaluate the tissue toxicity after gene transfer. The reporter genes expression in the liver dramatically increased after PVI + TVE in comparison to after PVI alone (1.2 x 10(5)versus 1.5 x 10(4) RLU/mg protein, P HVJ-liposome method and this modality might also be applicable to other gene transfer systems.

  20. Light Microscopic Evaluation of Cardio-vasculare System in Alloksan-induced Diabetic Rats in Acute Period

    Directory of Open Access Journals (Sweden)

    Selen Bahçeci

    2007-01-01

    Full Text Available Diabetic cardiomyopathy is one of the chronic complication of diabetes and acute effects of diabetes on heart and aorta is not clear. We aimed to determine acute effects of diabetes on cardio-vasculare system with light microscopy. We used 20 Spraque-Dawley rats and applied 150 mg/kg alloxan, intraperitoneally for inducing diabetes and 1 ml SF in control group. After 24 hours, venous blood samples were measured. Blood glucose levels higher than 250 mg/dl were accepted as DM and treated with 4 IU/d human insülin. After 7 days rats were sacrified under ketamin anaesthesia. Heart and aorta were fixed in 10 % buffered formalin. The sectiones were embedded in paraffin and were serially sectioned at 5 m thickness, then stained with Hematoxyline-Eosine (H&E and Heidenhein’s Azan modification.There was no histopathological changes in cardiac muscle cells in control group. But there was a heterogen appearance in cardiac muscle cells and we determined some hydropic degenerations in some of the cardiac muscle cells and a minimal fibrosis in perivasculare and interstitial area in diabetic group. All histological stratums of aorta were seen normally in control group. In diabetic group, there was a clear anisostosis in smooth muscle cells and decreased in nucleus of smooth muscle cells in tunica media. We concluted that DM is caused degeneration and fibrosis in cardiac muscle cells and effective on smooth muscle cells in aorta in acute period.

  1. Early Intervention of Didang Decoction on MLCK Signaling Pathways in Vascular Endothelial Cells of Type 2 Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Shoujiao Ye

    2016-01-01

    Full Text Available In the study, type 2 diabetic rat model was established using streptozotocin (STZ combined with a high-fat diet, and the rats were divided into control and diabetic groups. Diabetic groups were further divided into nonintervening, simvastatin, Didang Decoction (DDD early-phase intervening, DDD mid-phase intervening, and DDD late-phase intervening groups. The expression level of MLCK was detected using Western Blot analysis, and the levels of cyclic adenosine monophosphate (cAMP, protein kinase C (PKC, and protein kinase A (PKA were examined using Real Time PCR. Under the electron microscope, the cells in the early-DDD-intervention group and the simvastatin group were significantly more continuous and compact than those in the diabetic group. Compared with the control group, the expression of cAMP-1 and PKA was decreased in all diabetic groups, whereas the expression of MLCK and PKC was increased in early- and mid-phase DDD-intervening groups (P<0.05; compared with the late-phase DDD-intervening group, the expression of cAMP-1 and PKA was higher, but the level of MLCK and PKC was lower in early-phase DDD-intervening group (P<0.05. In conclusion, the early use of DDD improves the permeability of vascular endothelial cells by regulating the MLCK signaling pathway.

  2. Vascular endothelial growth factor receptor-2 inhibitor cediranib causes regression of endometriotic lesions in a rat model

    Science.gov (United States)

    Liu, Fang; Wang, Li; Zhang, Xian-Xia; Min, Shu-Yun; Liu, Yi-Xuan; Zuo, Zhi; Jin, Zhi-Xing; Zhu, Zhi-Ling

    2015-01-01

    Vascular endothelial growth factor (VEGF) receptor-2 plays an essential role in angiogenesis, and it also expressed in the glandular epithelium and stromal cells of ectopic endometrium. Cediranib is a protein tyrosine kinase inhibitor that potently inhibits VEGF receptor-2, but there is no study about its effects on the endometriosis. We induced endometriosis on both sides of the abdominal wall in 20 female Sprague-Dawley rats and randomly divided them into 2 groups. They were administered: cediranib 4 mg/kg/day (group 1), equal saline (group 2) for 12 days. Then, the lesion volumes were calculated, and Masson trichrome was used to detect fibrosis. Angiogenesis was evaluated by CD-31 immunohistochemistry and serum VEGF levels. Proliferation was indicated by proliferating cell nuclear antigen immunohistochemistry. Apoptosis was measured by a TUNEL assay and cleaved caspase-3 immunohistochemistry. In the treatment group, the lesion volumes were smaller (P < 0.05), and the degree of fibrosis was greater. The microvessel density was lower (P < 0.05) than control, however, serum VEGF was up-regulated by a negative feedback mechanism (P < 0.01). In addition, proliferation was significantly suppressed (P < 0.01), and apoptosis in the lesions was more obvious in the treatment group. These data indicated that cediranib can inhibit development of endometriotic lesions in rats. PMID:25973002

  3. Cultured rat vascular smooth muscle cells are resistant to methylamine toxicity: no correlation to semicarbazide-sensitive amine oxidase

    Science.gov (United States)

    Langford, S. D.; Trent, M. B.; Boor, P. J.

    2001-01-01

    Methylamine (MA), a component of serum and a metabolite of nicotine and certain insecticides and herbicides, is metabolized by semicarbazide-sensitive amine oxidase (SSAO). MA is toxic to cultured human umbilical vein and calf pulmonary artery endothelial cells. Endothelial cells, which do not exhibit endogenous SSAO activity, are exposed to SSAO circulating in serum. In contrast, vascular smooth muscle cells (VSMC) do exhibit innate SSAO activity both in vivo and in vitro. This property, together with the critical localization of VSMC within the arterial wall, led us to investigate the potential toxicity of MA to VSMC. Cultured rat VSMC were treated with MA (10-5 to 1 M). In some cultures, SSAO was selectively inhibited with semicarbazide or MDL-72145 [(E)-2-(3,4-dimethoxyphenyl)-3-fluoroallylamine]. Cytotoxicity was measured via MTT, vital dye exclusion, and clonogenic assays. MA proved to be toxic to VSMC only at relatively high concentrations (LC(50) of 0.1 M). The inhibition of SSAO with semicarbazide or MDL-72145 did not increase MA toxicity, suggesting that the production of formaldehyde via tissue-bound, SSAO-mediated MA metabolism does not play a role in the minimal toxicity observed in isolated rat VSMC. The omission of fetal calf serum (FCS), which contains high SSAO activity, from media similarly showed little effect on cytotoxicity. We conclude that VSMC--in contrast to previous results in endothelial cells--are relatively resistant to MA toxicity, and SSAO does not play a role in VSMC injury by MA.

  4. Hydrogen peroxide prevents vascular calcification induced ROS production by regulating Nrf-2 pathway.

    Science.gov (United States)

    Zhang, Wensong; Li, Yi; Ding, Hanlu; Du, Yaqin; Wang, Li

    2016-08-01

    Although vascular calcification in end-stage renal disease (ESRD) represents a ubiquitous human health problem, effective therapies with limited side effects are still lacking, and the precise mechanisms are not fully understood. The Nrf-2/ARE pathway is a pivotal to regulate anti-oxidative responses in vascular calcification upon ESRD. Although Nrf-2 plays a crucial role in atherosclerosis, pulmonary fibrosis, and brain ischemia, the effect of Nrf-2 and oxidative stress on vascular calcification in ESRD patients is still unclear. The aim of this research was to study the protective role of hydrogen peroxide in vascular calcification and the mechanism of Nrf-2 and oxidative stress on vascular calcification. Here we used the rat vascular smooth muscle cell model of β-glycerophosphate-induced calcification resembling vascular calcification in ESRD to investigate the therapeutic effect of 0.01 mM hydrogen peroxide on vascular calcification and further explores the possible underlying mechanisms. Our current report shows the in vitro role of 0.01 mM hydrogen peroxide in protecting against intracellular ROS accumulation upon vascular calcification. Both hydrogen peroxide and sulforaphane pretreatment reduced ROS production, increased the expression of Nrf-2, and decreased the expression of Runx2 following calcification. Our study demonstrates that 0.01 mM hydrogen peroxide can effectively protect rat aortic vascular smooth muscle cells against oxidative stress by preventing vascular calcification induced ROS production through Nrf-2 pathway. These data might define an antioxidant role of hydrogen peroxide in vascular calcification upon ESRD.

  5. A 3-month age difference profoundly alters the primary rat stromal vascular fraction phenotype

    DEFF Research Database (Denmark)

    Quaade, Marlene Louise; Jensen, Charlotte Harken; Andersen, Ditte Caroline

    2016-01-01

    such as age is demanded. Here we report that even a short age difference has an impact on the phenotype of primary SVF cells. We observed that a 3-month difference in relatively young adult rats affects the expression pattern of several mesenchymal stem cell markers in their primary SVF. The younger animals...

  6. Differential expression of BK channel isoforms and beta-subunits in rat neuro-vascular tissues

    DEFF Research Database (Denmark)

    Poulsen, Asser Nyander; Wulf, Helle; Hay-Schmidt, Anders

    2009-01-01

    We investigated the expression of splice variants and beta-subunits of the BK channel (big conductance Ca(2+)-activated K(+) channel, Slo1, MaxiK, K(Ca)1.1) in rat cerebral blood vessels, meninges, trigeminal ganglion among other tissues. An alpha-subunit splice variant X1(+24) was found expressed...

  7. Aortic Valve Stenosis

    Science.gov (United States)

    ... rapid, fluttering heartbeat Not eating enough (mainly in children with aortic valve stenosis) Not gaining enough weight (mainly in children with aortic valve stenosis) The heart-weakening effects of aortic valve stenosis ...

  8. Acute Ozone (O3) Exposure Enhances Aortic Contraction in Healthy Rats while Exacerbating Pulmonary Injury in Diabetics

    Science.gov (United States)

    Air pollution exposure affects health adversely in individuals with type 2 diabetes (T2D) and diet induced obesity (DIO). We hypothesized that T2D and DIO would exacerbate O3 induced pulmonary responses and alter arterial reactivity. Male Wistar and Goto Kakizaki (GK) rats, a l...

  9. DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

    Directory of Open Access Journals (Sweden)

    Xavier eLópez-Gil

    2014-07-01

    Full Text Available The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm3 isometric resolution at 10, 14, 18, 22, 26 and 40 weeks after birth. Diffusion weighted imaging was analyzed in 2 different ways, by regional characterization of diffusion tensor imaging indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, diffusion tensor imaging scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and grey matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional 3-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

  10. Neuroprotection, learning and memory improvement of a standardized extract from Renshen Shouwu against neuronal injury and vascular dementia in rats with brain ischemia.

    Science.gov (United States)

    Wan, Li; Cheng, Yufang; Luo, Zhanyuan; Guo, Haibiao; Zhao, Wenjing; Gu, Quanlin; Yang, Xu; Xu, Jiangping; Bei, Weijian; Guo, Jiao

    2015-05-13

    The Renshen Shouwu capsule (RSSW) is a patented Traditional Chinese Medicine (TCM), that has been proven to improve memory and is widely used in China to apoplexy syndrome and memory deficits. To investigate the neuroprotective and therapeutic effect of the Renshen Shouwu standardized extract (RSSW) on ischemic brain neuronal injury and impairment of learning and memory related to Vascular Dementia (VD) induced by a focal and global cerebral ischemia-reperfusion injury in rats. Using in vivo rat models of both focal ischemia/reperfusion (I/R) injuries induced by a middle cerebral artery occlusion (MCAO), and VD with transient global brain I/R neuronal injuries induced by a four-vessel occlusion (4-VO) in Sprague-Dawley (SD) rats, RSSW (50,100, and 200 mg kg(-1) body weights) and Egb761® (80 mg kg(-1)) were administered orally for 20 days (preventively 6 days+therapeutically 14 days) in 4-VO rats, and for 7 days (3 days preventively+4 days therapeutically) in MCAO rats. Learning and memory behavioral performance was assayed using a Morris water maze test including a place navigation trial and a spatial probe trial. Brain histochemical morphology and hippocampal neuron survival was quantified using microscope assay of a puffin brain/hippocampus slice with cresyl violet staining. MCAO ischemia/reperfusion caused infarct damage in rat brain tissue. 4-VO ischemia/reperfusion caused a hippocampal neuronal lesion and learning and memory deficits in rats. Administration of RSSW (50, 100, and 200mg/kg) or EGb761 significantly reduced the size of the insulted brain hemisphere lesion and improved the neurological behavior of MCAO rats. In addition, RSSW markedly reduced an increase in the brain infarct volume from an I/R-induced MCAO and reduced the cerebral water content in a dose-dependent way. Administration of RSSW also increased the pyramidal neuronal density in the hippocampus of surviving rats after transient global brain ischemia and improved the learning and memory

  11. Bicuspid Aortic Valve

    Science.gov (United States)

    2006-08-01

    aortic valvular disease, endocarditis, ascending aortic aneurysm and aortic dissection.1-4 There is also an association of BAV with coarctation of...for aortic aneurysm , patients with BAV appear to have additional risks for aortic disease. Nistri et al.12 reported significant aortic root...Congenital heart disease in patients with Turner’s syndrome. Italian study group for Turner syndrome (ISGTS). J Pediatr 1998; 133:688-692. 7. Schmid

  12. The role of losartan in preventing vascular remodeling in spontaneously hypertensive rats by inhibition of the H2O2/VPO1/HOCl/MMPs pathway.

    Science.gov (United States)

    Ge, Liangqing; Zhang, Guogang; You, Baiyang; Cheng, Guangjie; Chen, Luyao; Shi, Ruizheng

    2017-11-04

    Vascular peroxidase 1 (VPO1) has been proved to be associated with vascular endothelial cell apoptosis by producing reactive oxygen species. However, the contribution of VPO1 to the development of vascular remodeling (VR) remains to be fully characterized. We explored the role of VPO1 in VR in spontaneously hypertensive rats (SHRs) and the underlying mechanism of losartan in inhibiting VR. Compared to Wistar-Kyoto (WKY) rats, the SHR showed remodeling of their vascular walls. The level of VPO1 and the hydrogen peroxide (H2O2) concentration were increased in the SHRs. However, the SHRs pretreated with losartan showed significant inhibition of blood pressure and VR and decreased levels of VPO1 and H2O2 compared to the non-treated SHRs. Angiotensin II significantly increased the expressions of MMP-2, MMP-9 and the concentrations of H2O2 and hypochlorous acid (HOCl) in vascular smooth muscle cells (VSMCs). However, only the H2O2 level increased in VSMCs when transfected with VPO1 shRNA. These results support a critical but previously unrecognized role of VPO1 in VR and suggest that therapies to reduce VPO1 may be novel approaches for VR. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Protective Effect of Low-Intensity Pulsed Ultrasound on Memory Impairment and Brain Damage in a Rat Model of Vascular Dementia.

    Science.gov (United States)

    Huang, Sin-Luo; Chang, Chi-Wei; Lee, Yi-Hsuan; Yang, Feng-Yi

    2017-01-01

    Purpose To investigate the neuroprotective effects of low-intensity pulsed (LIP) ultrasound on memory impairment and central nervous system injury in a rat model of vascular dementia. Materials and Methods All animal experiments were approved by the animal care and use committee and adhered to experimental animal care guidelines. A 1.0-MHz focused ultrasound transducer was used to stimulate the brain noninvasively with 50-msec bursts at a 5% duty cycle, repetition frequency of 1 Hz, and spatial peak temporal average intensity of 528 mW/cm(2). LIP ultrasound treatment was performed daily with triple sonications in each hemisphere. The duration of each sonicaton was 5 minutes, with a 5-minute interval between each sonication. Permanent bilateral common carotid artery occlusion (BCCAO) was used as a model of vascular dementia. After 2 weeks of LIP ultrasound, neuroprotective effects of LIP ultrasound were evaluated with behavioral analysis, including the passive avoidance task and elevated plus maze. Myelin content was detected with carbon 11 ((11)C) Pittsburgh compound B (PIB). Brain sections were stained with hematoxylin-eosin and Luxol fast blue. Two-way analysis of variance and Student t test were used for statistical analyses, with a significance level of .05. Results Protein expressions of brain-derived neurotrophic factor (BDNF) in the BCCAO rats treated with LIP ultrasound were significantly higher than those in BCCAO rats (1.1 ± 0.0 vs 0.8 ± 0.1, P vascular dementia compared with rats with untreated vascular dementia (P vascular dementia. The beneficial effect of LIP ultrasound may be partly induced by upregulation of protein expression of BDNF. (©) RSNA, 2016.

  14. Loss of arterial and renal nitric oxide bioavailability in hypertensive rats with diabetes: effect of beta-blockers.

    Science.gov (United States)

    Mason, R Preston; Kubant, Ruslan; Jacob, Robert F; Malinski, Peter; Huang, Xiaoyan; Louka, Febee R; Borowiec, Jan; Mizuno, Yoshiko; Malinski, Tadeusz

    2009-11-01

    Endothelial cell (EC) dysfunction contributes to hypertension and mechanisms of atherosclerosis. Agents that improve EC function may provide vascular protection, especially in patients with multiple risk factors. In this study, we examined the effects of beta(1)-selective antagonists, nebivolol and metoprolol, on vascular and renal EC function in spontaneously hypertensive (SH) rats with diabetes. Male SH rats were treated with streptozotocin (STZ) to induce type 2 diabetes, followed by treatment with nebivolol or metoprolol at 2 mg/kg/day (vs. vehicle). After 4 weeks, aortic and glomerular ECs were isolated, stimulated with calcium ionophore (CaI), and assayed for nitric oxide (NO), and peroxynitrite (ONOO(-)) release using amperometric approaches. Glucose and mean blood pressure (BP) levels were significantly elevated in diabetic SH rats. In aortic ECs isolated from diabetic SH rats, NO production decreased by 20% whereas ONOO(-) increased by 16%, an effect linked to NAD(P)H oxidase and endothelial NO synthase (eNOS) uncoupling. Nebivolol treatment reduced glucose and BP levels and restored aortic EC function in diabetic SH rats, as indicated by a 30% increase and 23% decrease in NO and ONOO(-) levels, respectively. The NO/ONOO(-) ratio increased by more than twofold with nebivolol treatment in aortic and glomerular ECs. Despite similar reductions in glucose and mean BP levels, metoprolol had a smaller effect on the NO/ONOO(-) ratio in glomerular ECs but no effect in aortic ECs. Vascular and renal NO was significantly reduced in diabetic hypertensive rats and correlated with metabolic changes. Nebivolol reversed these effects in a manner consistent with enhanced endothelial function.

  15. Pregnancy-associated reduction in vascular protein kinase C activity rebounds during inhibition of NO synthesis.

    Science.gov (United States)

    Kanashiro, C A; Cockrell, K L; Alexander, B T; Granger, J P; Khalil, R A

    2000-02-01

    Vascular reactivity has been shown to be reduced during pregnancy and to be enhanced during chronic inhibition of nitric oxide (NO) synthesis in pregnant rats; however, the cellular mechanisms involved are unclear. The purpose of this study was to investigate whether the pregnancy-induced changes in vascular reactivity are associated with changes in the amount and/or activity of vascular protein kinase C (PKC). Active stress as well as the amount and activity of PKC was measured in deendothelialized thoracic aortic strips from virgin and pregnant rats untreated or treated with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). In virgin rats, the PKC activator phorbol 12,13-dibutyrate (PDBu, 10(-6) M) and the alpha-adrenergic agonist phenylephrine (Phe, 10(-5) M) caused significant increases in active stress and PKC activity that were inhibited by the PKC inhibitors staurosporine and calphostin C. Western blot analysis in aortic strips of virgin rats showed significant amount of the alpha-PKC isoform. Both PDBu and Phe caused significant translocation of alpha-PKC from the cytosolic to the particulate fraction. Compared with virgin rats, the PDBu- and Phe-stimulated active stress and PKC activity as well as the amount and the PDBu- and Phe-induced translocation of alpha-PKC were significantly reduced in late pregnant rats but significantly enhanced in pregnant rats treated with L-NAME. The PDBu- and Phe-induced changes in active stress and the amount, distribution, and activity of alpha-PKC in virgin rats treated with L-NAME were not significantly different from that in virgin rats, whereas the changes in pregnant rats treated with L-NAME + the NO synthase substrate L-arginine were not significantly different from that in pregnant rats. These results provide evidence that a PKC-mediated contractile pathway in vascular smooth muscle is reduced during pregnancy and significantly enhanced during chronic inhibition of NO synthesis. The results

  16. HZE ⁵⁶Fe-ion irradiation induces endothelial dysfunction in rat aorta: role of xanthine oxidase.

    Science.gov (United States)

    Soucy, Kevin G; Lim, Hyun Kyo; Kim, Jae Hyung; Oh, Young; Attarzadeh, David O; Sevinc, Baris; Kuo, Maggie M; Shoukas, Artin A; Vazquez, Marcelo E; Berkowitz, Dan E

    2011-10-01

    Ionizing radiation has been implicated in the development of significant cardiovascular complications. Since radiation exposure is associated with space exploration, astronauts are potentially at increased risk of accelerated cardiovascular disease. This study investigated the effect of high atomic number, high-energy (HZE) iron-ion radiation on vascular and endothelial function as a model of space radiation. Rats were exposed to a single whole-body dose of iron-ion radiation at doses of 0, 0.5 or 1 Gy. In vivo aortic stiffness and ex vivo aortic tension responses were measured 6 and 8 months after exposure as indicators of chronic vascular injury. Rats exposed to 1 Gy iron ions demonstrated significantly increased aortic stiffness, as measured by pulse wave velocity. Aortic rings from irradiated rats exhibited impaired endothelial-dependent relaxation consistent with endothelial dysfunction. Acute xanthine oxidase (XO) inhibition or reactive oxygen species (ROS) scavenging restored endothelial-dependent responses to normal. In addition, XO activity was significantly elevated in rat aorta 4 months after whole-body irradiation. Furthermore, XO inhibition, initiated immediately after radiation exposure and continued until euthanasia, completely inhibited radiation-dependent XO activation. ROS production was elevated after 1 Gy irradiation while production of nitric oxide (NO) was significantly impaired. XO inhibition restored NO and ROS production. Finally, dietary XO inhibition preserved normal endothelial function and vascular stiffness after radiation exposure. These results demonstrate that radiation induced XO-dependent ROS production and nitroso-redox imbalance, leading to chronic vascular dysfunction. As a result, XO is a potential target for radioprotection. Enhancing the understanding of vascular radiation injury could lead to the development of effective methods to ameliorate radiation-induced vascular damage.

  17. Polydeoxyribonucleotide administration improves the intra-testicular vascularization in rat experimental varicocele.

    Science.gov (United States)

    Arena, Salvatore; Minutoli, Letteria; Arena, Francesco; Nicotina, Piero Antonio; Romeo, Carmelo; Squadrito, Francesco; Altavilla, Domenica; Morgia, Giuseppe; Magno, Carlo

    2012-01-01

    To study the effect of PDRN on angiogenesis in a model of varicocele in rats. After the creation of experimental varicocele, rats were randomized to one of the four treatments: vehicle, PDRN, DMPX, and PDRN plus DMPX. Twenty-one days after randomization, all animals were euthanized and the left testis was harvested. Academic hospital. Male Sprague-Dawley rats were used. A clamp was passed behind the left renal vein distally to the spermatic vein insertion. A silk ligature was placed around the left renal vein at this site and was tied over the top of a probe. The latter was then withdrawn and the vein was allowed to expand. In shams, a suture was placed but it was not tied. To assess testicular microvascular density using CD34 immunostaining. Microvascular density in the varicocele plus PDRN group was significantly higher than in other groups. PDRN could represent a novel therapeutic strategy for varicocele treatment in subfertile patients, improving the innate pathophysiologic mechanism of neoangiogenesis, through compensatory oxygen and metabolite supply to tubular and extratubular testicular compartments. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Musculus gastrocnemius tetanus kinetics in alcohol-intoxicated rats with experimentally-induced hindlimb vascular ischemia under conditions of low-frequence muscle fatigue

    Directory of Open Access Journals (Sweden)

    O. A. Melnychuk

    2014-04-01

    Full Text Available Alcohol intoxication and ischemic injury of skeletal muscles often accompany each other. It is shown that patients hospitalized with chronic alcoholism develop muscle fatigue. Skeletal muscle dysfunction in alcohol-dependent patients is caused by ethanol-associated myofibrillar atrophy and metabolic disbalance, while compression-ischemic lesions result from unconsciousness of the patient, in case of taking the critical alcohol dose. Therefore, the aim of this study is to discover typical m. gastrocnemius (cap. med. tetanic kinetics changes in alcohol intoxicated rats with experimentally induced vascular ischemia of hindlimb muscles under conditions of low-frequency progressive muscle fatigue. Experiments were carried out on 10 young male Wistar rats (149.5 ± 5.8 g kept under standard vivarium conditions and diet. The investigation was conducted in two phases: chronic (30 days and acute (3 hours experiment. All surgical procedures were carried out aseptically under general anesthesia. Ishemic m. gastrocnemius (cap. med. tetanic kinetic changes and force productivity in alcohol intoxicated rats were investigated in the isometric mode, with direct electrical stimulation. The fatigue of m. gastrocnemius (cap. med. was evaluated by three characteristic criteria: the first sag effect, the secondary force rise, the second sag effect. There have been 10 similar experiments: 5 series in each study group with 10 tetanic runs in each series. The highest amplitude of the native m. gastrocnemius (cap. med. tetanus relative to isoline was taken as 100% force response. The same pattern of m. gastrocnemius (cap. med. low-frequency fatigue development was found in both rat groups under study. It is evidenced by the absence of substantial m. gastrocnemius (cap. med. tetanus kinetics differences in alcohol intoxicated rats, compared with non-alcohol intoxicated rats during fatigue test. However, the appreciable m. gastrocnemius (cap. med. tetanic force reduction

  19. WNK1 is required for proliferation induced by hypotonic challenge in rat vascular smooth muscle cells.

    Science.gov (United States)

    Zhang, Ya-Juan; Zheng, Hua-Qing; Chen, Bao-Yi; Sun, Lu; Ma, Ming-Ming; Wang, Guan-Lei; Guan, Yong-Yuan

    2018-01-01

    Hypotonic challenge evoked vascular cell proliferation through activation of volume-regulated Cl - channel (VRCC), leading to a decrease in the intracellular Cl - concentration ([Cl - ] i ). We hypothesize that the decrease in [Cl - ] i may activate one or several Cl - -sensitive kinases, resulting in a subsequent signaling cascade. In this study we demonstrated that WNK1, a Cl - -sensitive kinase, was involved in VRCC-induced proliferative signaling pathway in A10 vascular smooth muscle cells in vitro. A10 cells were exposed to a hypotonic challenge (225 mosmol·kg -1 ·H 2 0), which caused significantly increase in WNK1 phosphorylation without altering WNK1 protein expression. WNK1 overexpression significantly increased hypotonic-induced A10 cell proliferation, whereas silencing of WNK1 caused an opposite action. WNK1 mutation did not affect hypotonic-induced WNK1 phosphorylation and cell proliferation. Silencing of WNK1 caused cell cycle arrest at G 0 /G 1 phase and prevented transition from G 1 to S phase, whereas the WNK1 overexpression accelerated cell cycle transition from G 1 to S phase. Silencing of WNK1 significantly inhibited cyclin D1/cyclin E1 expression and increased p27kip/p21cip expression. WNK1 overexpression significantly increased cyclin D1/cyclin E1 expression and reduced p27 KIP /p21 CIP expression. In addition, WNK1 knockdown or overexpression significantly attenuated or increased the hypotonic-induced phosphorylation of Akt and PI3K respectively.In conclusion, the reduction in [Cl - ] i caused by hypotonic challenge-induced VRCC opening evokes WNK1 phosphorylation in A10 VSMCs, which mediates cell cycle transition from G 0 /G 1 to S phase and proliferation through the PI3K-Akt signaling pathway.

  20. Expressions of endoplasmic reticulum stress related protein, hypoxia-inducible factor-1α and vascular endothelial growth factor in the retina of diabetic rats

    OpenAIRE

    Jing Wang; Hong Zhu; Cai-Hong Shi

    2015-01-01

    AIM: To evaluate the expressions and significances of endoplasmic reticulum stress related protein(BIP), hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)in the retina of diabetic rats.METHODS: Seventy-two male Sprague-Dawley(SD)rats were chosen and divided randomly into 6 groups: normal control 2mo(C2m, n=12), diabetes mellitus 2mo(D2m, n=12), normal control 4mo(C4m, n=12), diabetes mellitus 4mo(D4m, n=12), normal control 6mo(C6m, n=12)and diabetes mellitus 6mo(...

  1. Abdominal aortic aneurysms: an autoimmune disease?

    Science.gov (United States)

    Jagadesham, Vamshi P; Scott, D Julian A; Carding, Simon R

    2008-12-01

    Abdominal aortic aneurysms (AAAs) are a multifactorial degenerative vascular disorder. One of the defining features of the pathophysiology of aneurysmal disease is inflammation. Recent developments in vascular and molecular cell biology have increased our knowledge on the role of the adaptive and innate immune systems in the initiation and propagation of the inflammatory response in aortic tissue. AAAs share many features of autoimmune disease, including genetic predisposition, organ specificity and chronic inflammation. Here, this evidence is used to propose that the chronic inflammation observed in AAAs is a consequence of a dysregulated autoimmune response against autologous components of the aortic wall that persists inappropriately. Identification of the molecular and cellular targets involved in AAA formation will allow the development of therapeutic agents for the treatment of AAA.

  2. Endovascular aortic repair: First twenty years

    Directory of Open Access Journals (Sweden)

    Končar Igor

    2012-01-01

    Full Text Available Endovascular aortic/aneurysm repair (EVAR was introduced into clinical practice at the beginning of the nineties. Its fast development had a great influence on clinicians, vascular surgeons and interventional radiologists, educational curriculums, patients, industry and medical insurance. The aim of this paper is to present the contribution of clinicians and industry to the development and advancement of endovascular aortic repair over the last 20 years. This review article presents the development of EVAR by focusing on the contribution of physicians, surgeons and interventional radiologists in the creation of the new field of vascular surgery termed hybrid vascular surgery, and also the contribution of technological advancement by a significant help of industrial representatives – engineers and their counselors. This article also analyzes studies conducted in order to compare the successfulness of EVAR with up-to-now applied open surgical repair of aortic aneurysms, and some treatment techniques of other aortic diseases. During the first two decades of its development the EVAR met