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Sample records for resistance arterial contractile

  1. The Effect of Creatine Kinase Inhibition on Contractile Properties of Human Resistance Arteries

    NARCIS (Netherlands)

    Taherzadeh, Zhila; Karamat, Fares A.; Ankum, Willem M.; Clark, Joseph F.; van Montfrans, Gert A.; van Bavel, Ed; Brewster, Lizzy M.

    2016-01-01

    Creatine kinase (CK) is a main predictor of blood pressure, and this is thought to largely depend on high resistance artery contractility. We previously reported an association between vascular contractility and CK in normotensive pregnancy, but pregnancy is a strong CK inducer, and data on human

  2. Effect of heart rate and myocardial contractile force on coronary resistance.

    OpenAIRE

    Saito, Daiji; Ueeda, Masayuki; Hina, Kazuyoshi; Watanabe, Hirofumi; Mima, Tsutomu; Hasui, Masahiro; Yamada, Nobuyuki; Haraoka, Shoichi; Tsuji, Takao

    1988-01-01

    The effect of the heart rate and myocardial contractile force on the extravascular resistance to blood flow of the left anterior descending coronary artery (LAD) was evaluated in 15 mongrel dogs anesthetized with sodium pentobarbital. The LAD was maximally dilated by intracoronary infusion of adenosine, which precluded the influence of vasomotor tone. Increases in the heart rate and myocardial contractile force decreased coronary blood flow in the absence of a change in coronary perfusion pre...

  3. Upregulation of ERK1/2-eNOS via AT2 receptors decreases the contractile response to angiotensin II in resistance mesenteric arteries from obese rats.

    Directory of Open Access Journals (Sweden)

    Graziela N Hagihara

    Full Text Available It has been clearly established that mitogen-activated protein kinases (MAPKS are important mediators of angiotensin II (Ang II signaling via AT1 receptors in the vasculature. However, evidence for a role of these kinases in changes of Ang II-induced vasoconstriction in obesity is still lacking. Here we sought to determine whether vascular MAPKs are differentially activated by Ang II in obese animals. The role of AT2 receptors was also evaluated. Male monosodium glutamate-induced obese (obese and non-obese Wistar rats (control were used. The circulating concentrations of Ang I and Ang II, determined by HPLC, were increased in obese rats. Ang II-induced isometric contraction was decreased in endothelium-intact resistance mesenteric arteries from obese compared with control rats and exhibited a retarded AT1 receptor antagonist response. Blocking of AT2 receptors and inhibition of either endothelial nitric oxide synthase (eNOS or extracellular signal-regulated protein kinases 1 and 2 (ERK1/2 restored Ang II-induced contraction in obese rats. Western blot analysis revealed increased protein expression of AT2 receptors in arteries from obese rats. Basal and Ang II-induced ERK1/2 phosphorylation was also increased in obese rats. Blockade of either AT1 or AT2 receptors corrected the increased ERK1/2 phosphorylation in arteries from obese rats to levels observed in control preparations. Phosphorylation of eNOS was increased in obese rats. Incubation with the ERK1/2 inhibitor before Ang II stimulation did not affect eNOS phosphorylation in control rats; however, it corrected the increased phosphorylation of eNOS in obese rats. These results clearly demonstrate that enhanced AT2 receptor and ERK1/2-induced, NO-mediated vasodilation reduces Ang II-induced contraction in an endothelium-dependent manner in obese rats.

  4. Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice.

    Science.gov (United States)

    Rensen, Sander S; Niessen, Petra M; van Deursen, Jan M; Janssen, Ben J; Heijman, Edwin; Hermeling, Evelien; Meens, Merlijn; Lie, Natascha; Gijbels, Marion J; Strijkers, Gustav J; Doevendans, Pieter A; Hofker, Marten H; De Mey, Jo G R; van Eys, Guillaume J

    2008-08-19

    Smoothelins are actin-binding proteins that are abundantly expressed in healthy visceral (smoothelin-A) and vascular (smoothelin-B) smooth muscle. Their expression is strongly associated with the contractile phenotype of smooth muscle cells. Analysis of mice lacking both smoothelins (Smtn-A/B(-/-) mice) previously revealed a critical role for smoothelin-A in intestinal smooth muscle contraction. Here, we report on the generation and cardiovascular phenotype of mice lacking only smoothelin-B (Smtn-B(-/-)). Myograph studies revealed that the contractile capacity of the saphenous and femoral arteries was strongly reduced in Smtn-B(-/-) mice, regardless of the contractile agonist used to trigger contraction. Arteries from Smtn-A/B(-/-) compound mutant mice exhibited a similar contractile deficit. Smtn-B(-/-) arteries had a normal architecture and expressed normal levels of other smooth muscle cell-specific genes, including smooth muscle myosin heavy chain, alpha-smooth muscle actin, and smooth muscle-calponin. Decreased contractility of Smtn-B(-/-) arteries was paradoxically accompanied by increased mean arterial pressure (20 mm Hg) and concomitant cardiac hypertrophy despite normal parasympathetic and sympathetic tone in Smtn-B(-/-) mice. Magnetic resonance imaging experiments revealed that cardiac function was not changed, whereas distension of the proximal aorta during the cardiac cycle was increased in Smtn-B(-/-) mice. However, isobaric pulse wave velocity and pulse pressure measurements indicated normal aortic distensibility. Collectively, our results identify smoothelins as key determinants of arterial smooth muscle contractility and cardiovascular performance. Studies on mutations in the Smtn gene or alterations in smoothelin levels in connection to hypertension in humans are warranted.

  5. Prolonged ischemic heart disease and coronary artery bypass - relation to contractile reserve

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Bangsgaard, Regitze; Carstensen, Steen

    2002-01-01

    OBJECTIVE: A major effect of coronary artery bypass grafting (CABG) in patients with ischemic heart disease and impaired left ventricular (LV) contractile function is believed to be an improvement in LV function due to recovery of dysfunctional, but viable myocardium. However, recent studies have...

  6. Genetic fuzzy system predicting contractile reactivity patterns of small arteries

    DEFF Research Database (Denmark)

    Tang, J; Sheykhzade, Majid; Clausen, B F

    2014-01-01

    information. We developed a genetic fuzzy system (GFS) algorithm that is capable of learning all information in time-domain physiological data. Data on isometric force development of isolated small arteries were used as a framework for developing and optimizing a GFS. GFS performance was improved by several......Monitoring of physiological surrogate end points in drug development generates dynamic time-domain data reflecting the state of the biological system. Conventional data analysis often reduces the information in these data by extracting specific data points, thereby discarding potentially useful...

  7. Right ventricle contractility during early postoperative period after coronary artery bypass grafting with cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    А. Е. Баутин

    2015-10-01

    Full Text Available Emphasis in this research was placed on contractility of the right ventricle with regard to its relationship with systemic hemodynamics in patients undergoing coronary artery bypass grafting (CABG under cardiopulmonary bypass (CPB. The study included 25 patients (14 males, 11 females, mean age was 587 years admitted to ICU after CABG under CPB. All patients required inotropic therapy. The criterion for prescribing inotropic support in the postoperative period was a drop of the stroke volume index of the left ventricle below 35 ml/m 2 provided that the values of this indicator were normal before the perfusion period. Patients with previous pathology of the right ventricle or right coronary artery were excluded from the study. To evaluate the right ventricular function and systemic hemodynamics indicators, use was made of the PiCCO plus system and VoLEF addon device. It was found out that reduced contractility of the right ventricle may cause the reduction in stroke volume of the left ventricle with normal contractility. It was also observed that the increase of preload in patients with right ventricular ejection fraction less than 30% does not improve its function but leads to the increase of its end-diastolic volume. In 68% of cases, the need in inotropic agents in the early postoperative period after CABG was associated with the drop in right ventricle contractility, in 40% - with isolated right ven-tricular dysfunction. Patients with isolated reduction in right ventricle contractility required a longer period of inotropic support and ICU stay as compared with those with left ventricular failure.

  8. Prolonged ischemic heart disease and coronary artery bypass - relation to contractile reserve

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Bangsgaard, Regitze; Carstensen, Steen

    2002-01-01

    OBJECTIVE: A major effect of coronary artery bypass grafting (CABG) in patients with ischemic heart disease and impaired left ventricular (LV) contractile function is believed to be an improvement in LV function due to recovery of dysfunctional, but viable myocardium. However, recent studies have...... indicated a time limit for such a recovery. We therefore investigated the extent of viable myocardium in patients with impaired LV function due to ischemic heart disease after a prolonged strategy of medical treatment and its relation to changes in clinical variables after CABG. METHODS: Forty......-five consecutive patients with a mean duration of ischemic heart symptoms of 9 years and LV ejection fraction (EF) stress...

  9. Endothelin-1 and endothelin-2 initiate and maintain contractile responses by different mechanisms in rat mesenteric and cerebral arteries

    DEFF Research Database (Denmark)

    Compeer, M. G.; Janssen, G. M. J.; De Mey, J. G. R.

    2013-01-01

    , but relaxed ET-1-induced contractions in MRA. A PLC inhibitor prevented contractile responses to ET-1 and ET-2 in MRA and BA, and relaxed ET-1- and ET-2-induced responses in MRA and ET-1 effects in BA. A Rho-kinase inhibitor did not modify sensitivity, maximum and maintenance of responses to both peptides...... in both arteries but relaxed ET-2, but not ET-1, effects in MRA and ET-1 effects in BA. Conclusions and ImplicationsPLC played a key role in arterial contractile responses to ETs, but ET-1 and ET-2 initiated and maintained vasoconstriction through different mechanisms, and these differed between MRA...

  10. Prolonged ischemic heart disease and coronary artery bypass - relation to contractile reserve

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Bangsgaard, Regitze; Carstensen, Steen

    2002-01-01

    OBJECTIVE: A major effect of coronary artery bypass grafting (CABG) in patients with ischemic heart disease and impaired left ventricular (LV) contractile function is believed to be an improvement in LV function due to recovery of dysfunctional, but viable myocardium. However, recent studies have...... was correlated to the LV extent of myocardial metabolism--blood flow reverse mismatch. Most of the patients experienced an improvement in their angina pectoris, heart failure symptoms and exercise capacity after CABG; the overall 3-year survival was 77%. CONCLUSIONS: Patients with chronic ischemic heart disease...... indicated a time limit for such a recovery. We therefore investigated the extent of viable myocardium in patients with impaired LV function due to ischemic heart disease after a prolonged strategy of medical treatment and its relation to changes in clinical variables after CABG. METHODS: Forty...

  11. Altered contractile responses of arteries from spontaneously hypertensive rat: The role of endogenous mediators and membrane depolarization

    Czech Academy of Sciences Publication Activity Database

    Bencze, Michal; Behuliak, Michal; Vavřínová, Anna; Zicha, Josef

    2016-01-01

    Roč. 166, Dec 1 (2016), s. 46-53 ISSN 0024-3205 R&D Projects: GA ČR(CZ) GAP304/12/0259; GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : femoral artery * SHR * vascular contractility * adrenergic contraction * tyramine * propranolol * neuropeptide Y Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.936, year: 2016

  12. Spatial differences of cellular origins and in vivo hypoxia modify contractile properties of pulmonary artery smooth muscle cells: lessons for arterial tissue engineering.

    Science.gov (United States)

    Hall, S M; Soueid, A; Smith, T; Brown, R A; Haworth, S G; Mudera, V

    2007-01-01

    Tissue engineering of functional arteries is challenging. Within the pulmonary artery wall, smooth muscle cells (PASMCs) have site-specific developmental and functional phenotypes, reflecting differing contractile roles. The force generated by PASMCs isolated from the inner 25% and outer 50% of the media of intrapulmonary elastic arteries from five normal and eight chronically hypoxic (hypertensive) 14 day-old piglets was quantified in a three-dimensional (3D) collagen construct, using a culture force monitor. Outer medial PASMCs from normal piglets exerted more force (528 +/- 50 dynes) than those of hypoxic piglets (177 +/- 42 dynes; p engineering of major blood vessels.

  13. The effects of RSR13 on microvascular Po2 kinetics and muscle contractile performance in the rat arterial ligation model of peripheral arterial disease.

    Science.gov (United States)

    Watanabe, Aiko; Poole, David C; Kano, Yutaka

    2017-10-01

    Exercise intolerance and claudication are symptomatic of peripheral arterial disease. There is a close relationship between muscle O 2 delivery, microvascular oxygen partial pressure (P mv O 2 ), and contractile performance. We therefore hypothesized that a reduction of hemoglobin-oxygen affinity via RSR13 would maintain a higher P mv O 2 and enhance blood-muscle O 2 transport and contractile function. In male Wistar rats (12 wk of age), we created hindlimb ischemia via right-side iliac artery ligation (AL). The contralateral (left) muscle served as control (CONT). Seven days after AL, phosphorescence-quenching techniques were used to measure P mv O 2 at rest and during contractions (electrical stimulation; 1 Hz, 300 s) in tibialis anterior muscle (TA) under saline ( n = 10) or RSR13 ( n = 10) conditions. RSR13 at rest increased TA P mv O 2 in CONT (13.9 ± 1.6 to 19.3 ± 1.9 Torr, P < 0.05) and AL (9.0 ± 0.5 to 9.9 ± 0.7 Torr, P < 0.05). Furthermore, RSR13 extended maintenance of the initial TA force (i.e., improved contractile performance) such that force was not decreased significantly until contraction 240 vs. 150 in CONT and 80 vs. 20 in AL. This improved muscle endurance with RSR13 was accompanied by a greater ΔP mv O 2 (P mv O 2 decrease from baseline) (CONT, 7.4 ± 1.0 to 11.2 ± 1.3; AL, 6.9 ± 0.5 to 8.6 ± 0.6 Torr, both P < 0.05). Whereas RSR13 did not alter the kinetics profile of P mv O 2 (i.e., mean response time) substantially during contractions, muscle force was elevated, and the ratio of muscle force to P mv O 2 increased. In conclusion, reduction of hemoglobin-oxygen affinity via RSR13 in AL increased P mv O 2 and improved muscle contractile performance most likely via enhanced blood-muscle O 2 diffusion. NEW & NOTEWORTHY This is the first investigation to examine the effect of RSR13 (erythrocyte allosteric effector) on skeletal muscle microvascular oxygen partial pressure kinetics and contractile function using an arterial ligation model of

  14. Changes in biomechanical properties of the coronary artery wall contribute to maintained contractile responses to endothelin-1 in atherosclerosis.

    Science.gov (United States)

    Ooi, Chen Yen; Sutcliffe, Michael P F; Davenport, Anthony P; Maguire, Janet J

    2014-11-24

    Our aim was to determine whether alterations in biomechanical properties of human diseased compared to normal coronary artery contribute to changes in artery responsiveness to endothelin-1 in atherosclerosis. Concentration-response curves were constructed to endothelin-1 in normal and diseased coronary artery. The passive mechanical properties of arteries were determined using tensile ring tests from which finite element models of passive mechanical properties of both groups were created. Finite element modelling of artery endothelin-1 responses was then performed. Maximum responses to endothelin-1 were significantly attenuated in diseased (27±3 mN, n=55) compared to normal (38±2 mN, n=68) artery, although this remained over 70% of control. There was no difference in potency (pD2 control=8.03±0.06; pD2 diseased=7.98±0.06). Finite element modelling of tensile ring tests resulted in hyperelastic shear modulus μ=2004±410 Pa and hardening exponent α=22.8±2.2 for normal wall and μ=2464±1075 Pa and α=38.3±6.7 for plaque tissue and distensibility of diseased vessels was decreased. Finite element modelling of active properties of both groups resulted in higher muscle contractile strain (represented by thermal reactivity) of the atherosclerotic artery model than the normal artery model. The models suggest that a change in muscle response to endothelin-1 occurs in atherosclerotic artery to increase its distensibility towards that seen in normal artery. Our data suggest that an adaptation occurs in medial smooth muscle of atherosclerotic coronary artery to maintain distensibility of the vessel wall in the presence of endothelin-1. This may contribute to the vasospastic effect of locally increased endothelin-1 production that is reported in this condition. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Characterization of the contractile P2Y14 receptor in mouse coronary and cerebral arteries

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Edvinsson, Lars

    2014-01-01

    values and immunohistochemistry illustrated the strongest P2Y14 receptor expression in the basilar artery. In the presence of pertussis toxin, UDP-glucose inhibited contraction in coronary arteries and in the basilar artery it surprisingly caused relaxation. After organ culture of the coronary artery...

  16. Contractile responses to ergotamine and dihydroergotamine in the perfused middle cerebral artery of rat

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Nilsson, Elisabeth; Edvinsson, Lars

    2007-01-01

    , with pEC(50) values of 7.6+/-0.2 for ergotamine and 8.4+/-0.5 for DHE. The responses were blocked by the 5-HT(2A) receptor antagonist ketanserin (concentration 10(-12) to 10(-5) M) and partially with the 5-HT(1B) receptor antagonist BRL-11557PM-B. The 5-HT(1D) receptor antagonist SB-224289-A had...... no significant effect. Using a myograph technique, isolated ring segments of the MCA with intact endothelium were mounted on two metal wires. Neither agonist caused relaxation of resting vessels, however, they both responded by weak contractile responses (26+/-3% of submaximal contractile capacity relative to 60...

  17. Hypoxia and nitric oxide exposure promote apoptotic signaling in contractile pulmonary arterial smooth muscle but not in pulmonary epithelium.

    Science.gov (United States)

    Postolow, F; Fediuk, J; Nolette, N; Hinton, M; Dakshinamurti, S

    2011-12-01

    Neonatal pulmonary hypertension is characterized by hypoxia, abnormal vascular remodeling, and impaired alveolarization. Nitric oxide (NO) regulates cell replication and activation of apoptosis. Our objective was to examine cell phenotype-specific effects of hypoxia and NO exposure on cumulative apoptotic signal in neonatal pulmonary epithelial cells and arterial smooth muscle. Primary cultured newborn porcine pulmonary arterial myocytes and epithelial cells were grown in normoxic (21% O2) or hypoxic conditions (10% O2). Myocyte phenotype was predetermined by serum-supplementation or -deprivation. Cells were exposed to sodium nitroprusside (10(-7) -10(-4)  M) or diluent for 3 days. Cell survival was estimated by MTT assay; BAX, Bcl-2, and cleaved caspase-3 by Western blot; cell cycle entry by laser scanning cytometry. Hypoxic epithelial cells exhibited a small increase in anti-apoptotic Bcl2, and decrease in BAX. Cell survival and active caspase-3 were unchanged. Exposure to NO had no impact on epithelial apoptosis, but initiated necrosis. In contractile myocytes, pro-apoptotic BAX abundance and caspase-3 activation were increased by hypoxia, augmented by NO exposure promoting apoptosis. Hypoxia decreased BAX/Bcl-2 ratio and promoted survival of synthetic myocytes; NO increased apoptosis of normoxic synthetic myocytes, but decreased apoptosis of hypoxic synthetic myocytes. The effect of NO on pulmonary apoptosis is phenotype-dependent. A cumulative apoptotic effect of hypoxia and NO in vitro exerted on contractile myocytes may lead to contraction of this subpopulation, while synthetic myocyte survival and proliferation is enhanced by hypoxia and NO. Epithelial survival is unaffected. We speculate that alveolar rarefaction reported after neonatal hypoxia may arise from growth arrest in the vascular rather than the epithelial compartment. Copyright © 2011 Wiley Periodicals, Inc.

  18. Upregulation of contractile endothelin type B receptors by lipid-soluble cigarette smoking particles in rat cerebral arteries via activation of MAPK

    DEFF Research Database (Denmark)

    Sandhu, Hardip; Xu, Cang Bao; Edvinsson, Lars

    2010-01-01

    Cigarette smoke exposure increases the risk of stroke. However, the underlying molecular mechanisms are poorly understood. Endothelin system plays key roles in the pathogenesis of stroke. The present study was designed to examine if lipid-soluble (dimethyl sulfoxide-soluble) cigarette smoke parti...... and JNK MAPK-mediated transcription and translation of new contractile ET(B) receptors. Thus, the MAPK-mediated upregulation of contractile ET(B) receptors in cerebral arteries might be a pharmacological target for the treatment of smoke-associated cerebral vascular disease like stroke....

  19. Enhanced expression of contractile endothelin ET(B) receptors in rat coronary artery after organ culture

    DEFF Research Database (Denmark)

    Johnsson, E.; Maddahi, A.; Wackenfors, A.

    2008-01-01

    Endothelin-1 is a potent vasoconstrictor mediating its effects via two receptor subtypes, the endothelin type A (ET(A)) preferentially situated on smooth muscle cells, mediating vasoconstriction and endothelin type B (ET(B)) mainly located on endothelial cells, mediating vasodilatation....... In cardiovascular disease and in organ culture in vitro, endothelin ET(B) receptors are up-regulated on smooth muscle cells. The objectives of the present study were to characterise the endothelin receptor-induced vasoconstriction and quantify the endothelin receptor mRNA levels and immunoreactivity in fresh...... and cultured rat coronary arteries. We demonstrate that endothelin-1 induces strong and equal concentration-dependent contractions in fresh and cultured segments from the left anterior descending coronary artery. Sarafotoxin 6c, an endothelin ET(B) receptor agonist, had negligible effect in fresh arteries...

  20. Inactivation of the EP3 receptor attenuates the Angiotensin II pressor response via decreasing arterial contractility

    Science.gov (United States)

    Chen, Lihong; Miao, Yifei; Zhang, Yahua; Dou, Dou; Liu, Limei; Tian, Xiaoyu; Yang, Guangrui; Pu, Dan; Zhang, Xiaoyan; Kang, Jihong; Gao, Yuansheng; Wang, Shiqiang; Breyer, Matthew D.; Wang, Nanping; Zhu, Yi; Huang, Yu; Breyer, Richard M; Guan, Youfei

    2012-01-01

    Objective The present studies aimed at elucidating the role of prostaglandin E2 (PGE2) receptor subtype 3 (EP3) in regulating blood pressure. Methods and Results Mice bearing a genetic disruption of the EP3 gene (EP3−/−) exhibited reduced baseline mean arterial pressure monitored by both tail-cuff and carotid arterial catheterization. The pressor responses induced by EP3 agonists M&B28767 and sulprostone were markedly attenuated in EP3−/− mice, while the reduction of BP induced by PGE2 was comparable in both genotypes. Vasopressor effect of acute or chronic infusion of angiotensin II (AngII) was attenuated in EP3−/− mice. AngII–induced vasoconstriction in mesenteric arteries decreased in EP3−/− group. In mesenteric arteries from wild type mice, AngII–induced vasoconstriction was inhibited by EP3 selective antagonist DG-041 or L798106. The expression of Arhgef-1 is attenuated in EP3 deficient mesenteric arteries. EP3 antagonist DG-041 diminished AngII-induced phosphorylation of MLC20 and MYPT1 in isolated mesenteric arteries. Furthermore, in vascular smooth muscle cells (VSMCs), AngII induced intracellular Ca2+ increase was potentiated by EP3 agonist sulprostone, while inhibited by DG-041. Conclusions Activation of the EP3 receptor raises baseline blood pressure and contributes to AngII-dependent hypertension at least partially via enhancing Ca2+ sensitivity and intracellular calcium concentration in VSMCs. Selective targeting of the EP3 receptor may represent a potential therapeutic target for the treatment of hypertension. PMID:23065824

  1. Upregulation of contractile endothelin type B receptors by lipid-soluble cigarette smoking particles in rat cerebral arteries via activation of MAPK

    DEFF Research Database (Denmark)

    Sandhu, Hardip; Xu, Cang Bao; Edvinsson, Lars

    2010-01-01

    Cigarette smoke exposure increases the risk of stroke. However, the underlying molecular mechanisms are poorly understood. Endothelin system plays key roles in the pathogenesis of stroke. The present study was designed to examine if lipid-soluble (dimethyl sulfoxide-soluble) cigarette smoke...... or water-soluble cigarette smoke particles to the organ culture. The increased upregulation of contractile ET(B) receptors by DSP was abrogated by U0126, SP600125, actinomycin D, and cycloheximide, suggesting that the underlying molecular mechanisms involved in this process include activation of MEK...... and JNK MAPK-mediated transcription and translation of new contractile ET(B) receptors. Thus, the MAPK-mediated upregulation of contractile ET(B) receptors in cerebral arteries might be a pharmacological target for the treatment of smoke-associated cerebral vascular disease like stroke....

  2. Fetal Sheep Mesenteric Resistance Arteries: Functional and Structural Maturation.

    Science.gov (United States)

    Müller, Julia J; Schwab, Matthias; Rosenfeld, Charles R; Antonow-Schlorke, Iwa; Nathanielsz, Peter W; Rakers, Florian; Schubert, Harald; Witte, Otto W; Rupprecht, Sven

    2017-01-01

    Fetal blood pressure increases during late gestation; however, the underlying vascular mechanisms are unclear. Knowledge of the maturation of resistance arteries is important to identify the mechanisms and vulnerable periods for the development of vascular dysfunction in adulthood. We determined the functional and structural development of fetal sheep mesenteric resistance arteries using wire myography and immunohistochemistry. Media mass and distribution of myosin heavy-chain isoforms showed no changes between 0.7 (100 ± 3 days) and 0.9 (130 ± 3 days) gestation. However, from 0.7 to 0.9 gestation, the resting wall tension increased accompanied by non-receptor-dependent (potassium) and receptor-dependent (noradrenaline; endothelin-1) increases in vasocontraction. Angiotensin II had no contractile effect at both ages. Endothelium-dependent relaxation to acetylcholine and prostaglandin E2 was absent at 0.7 but present at 0.9 gestation. Augmented vascular responsiveness was paralleled by the maturation of sympathetic and sensory vascular innervation. Non-endothelium-dependent relaxation to nitric oxide showed no maturational changes. The expression of vasoregulator receptors/enzymes did not increase between 0.7 and 0.9 gestation. Vascular maturation during late ovine gestation involves an increase in resting wall tension and the vasoconstrictor and vasodilator capacity of the mesenteric resistance arteries. Absence of structural changes in the tunica media and the lack of an increase in vasoregulator receptor/enzyme expression suggest that vasoactive responses are due to the maturation of intracellular pathways at this gestational age. © 2017 S. Karger AG, Basel.

  3. Myocardial ischemia-reperfusion induces upregulation of contractile endothelin ETB receptor in rat coronary arteries

    DEFF Research Database (Denmark)

    Skovsted, Gry Freja; Sheykhzade, Majid; Trautner, Simon

    2011-01-01

    Objective We have previously shown increased expression of endothelin ETB receptors in coronary arteries of ischemic heart disease patients. ETB receptors are normal physiological conditions primarily situated in the vascular endothelial cells mediating vasodilation, whereas only a limited part...... to the specific ETB receptor agonist Sarafotoxin 6c (S6c) (1 pM to 30 nM) was investigated after cumulative additions in a sensitive wire-myograph. LAD segments, situated in the post-ischemic area displayed significantly augmented ETB receptor mediated vasoconstriction (68±3% of maximal contraction, n = 7......) compared to coronary arteries from the non-ischemic area (23±6 % of maximal contraction, n = 8) and sham operated rats (22±5% of maximal contraction, n = 5). Increased density of ETB receptors localized in the vascular smooth muscle layer was confirmed by immunohistochemistry in LAD segments from the post...

  4. Alteration in contractile G-protein coupled receptor expression by moist snuff and nicotine in rat cerebral arteries

    DEFF Research Database (Denmark)

    Sandhu, Hardip; Xu, Cang-Bao; Edvinsson, Lars

    2011-01-01

    The cardiovascular risk for users of use of Swedish snus/American snuff (moist tobacco) has been debated for a long time. The present study was designed to examine the effects of water- or lipid-soluble (DMSO-soluble) snus and nicotine, the most important substance in tobacco, on the expression...... kinases (MAPK). However, the effects of moist tobacco on the expression of GPCR are less studied. Rat middle cerebral arteries were isolated and organ cultured in serum-free medium for 24h in the presence of water-soluble snus (WSS), DMSO-soluble snus (DSS), or nicotine. The dose of snus and nicotine...... was kept at plasma level of snus users (25ng nicotine/ml). A high dose (250ng nicotine/ml) was also included due to the previous results showing alteration in the GPCR expression by nicotine at this concentration. Contractile responses to the ET(B) receptor agonist sarafotoxin 6c, 5-HT(1B) receptor agonist...

  5. Alteration in contractile G-protein coupled receptor expression by moist snus and nicotine in rat cerebral arteries

    International Nuclear Information System (INIS)

    Sandhu, Hardip; Xu Cangbao; Edvinsson, Lars

    2011-01-01

    The cardiovascular risk for users of use of Swedish snus/American snuff (moist tobacco) has been debated for a long time. The present study was designed to examine the effects of water- or lipid-soluble (DMSO-soluble) snus and nicotine, the most important substance in tobacco, on the expression of vasocontractile G-protein coupled receptors (GPCR), such as endothelin ET B , serotonin 5-HT 1B , and thromboxane A 2 TP receptors, in rat cerebral arteries. Studies show that these vasocontractile GPCR show alterations by lipid-soluble cigarette smoke particles via activation of mitogen-activated protein kinases (MAPK). However, the effects of moist tobacco on the expression of GPCR are less studied. Rat middle cerebral arteries were isolated and organ cultured in serum-free medium for 24 h in the presence of water-soluble snus (WSS), DMSO-soluble snus (DSS), or nicotine. The dose of snus and nicotine was kept at plasma level of snus users (25 ng nicotine/ml). A high dose (250 ng nicotine/ml) was also included due to the previous results showing alteration in the GPCR expression by nicotine at this concentration. Contractile responses to the ET B receptor agonist sarafotoxin 6c, 5-HT 1B receptor agonist 5-carboxamidotryptamine, and TP receptor agonist U46619 were investigated by a sensitive myograph. The expression of ET B , 5-HT 1B , and TP receptors was studied at mRNA and protein levels using quantitative real-time PCR and immunohistochemistry, respectively. Organ culture with WSS or DSS (25 ng nicotine/ml) lowered the 5-HT 1B receptor-mediated contraction. Furthermore, DSS shifted the TP receptor-mediated contraction curve left-wards with a stronger contraction. High dose of nicotine (250 ng nicotine/ml) increased the ET B receptor-mediated contraction. The combined 5-HT 1B and 5-HT 2A receptor-mediated contraction was increased, and both the 5-CT and TxA2 induced contractions were left-ward shifted by WSS, DSS, or nicotine (250 ng nicotine/ml). Only the DSS group

  6. Intestine of dystrophic mice presents enhanced contractile resistance to stretching despite morphological impairment.

    Science.gov (United States)

    Alves, Gabriel A; Silva, Luisa R; Rosa, Eloi F; Aboulafia, Jeannine; Freymüller-Haapalainen, Edna; Souccar, Caden; Nouailhetas, Viviane L A

    2014-02-01

    Protein dystrophin is a component of the dystrophin-associated protein complex, which links the contractile machinery to the plasma membrane and to the extracellular matrix. Its absence leads to a condition known as Duchenne muscular dystrophy (DMD), a disease characterized by progressive skeletal muscle degeneration, motor disability, and early death. In mdx mice, the most common DMD animal model, loss of muscle cells is observed, but the overall disease alterations are less intense than in DMD patients. Alterations in gastrointestinal tissues from DMD patients and mdx mice are not yet completely understood. Thus, we investigated the possible relationships between morphological (light and electron microscopy) and contractile function (by recording the isometric contractile response) with alterations in Ca²⁺ handling in the ileum of mdx mice. We evidenced a 27% reduction in the ileal muscular layer thickness, a partial damage to the mucosal layer, and a partial damage to mitochondria of the intestinal myocytes. Functionally, the ileum from mdx presented an enhanced responsiveness during stretch, a mild impairment in both the electromechanical and pharmacomechanical signaling associated with altered calcium influx-induced contraction, with no alterations in the sarcoplasmic reticulum Ca²⁺ storage (maintenance of the caffeine and thapsigargin-induced contraction) compared with control animals. Thus, it is evidenced that the protein dystrophin plays an important role in the preservation of both the microstructure and ultrastructure of mice intestine, while exerting a minor but important role concerning the intestinal contractile responsiveness and calcium handling.

  7. Bronchial arteries: an arteriosclerosis-resistant circulation.

    Science.gov (United States)

    Kotoulas, Christophoros; Melachrinou, Maria; Konstantinou, George N; Alexopoulos, Dimitrios; Dougenis, Dimitrios

    2010-01-01

    Until now, it is unknown whether and to what extent arteriosclerotic disease affects the bronchial arteries. We conducted this pilot study to estimate the prevalence of arteriosclerosis of the bronchial arteries, to correlate it with certain clinicolaboratory arteriosclerotic parameters or any coexistent coronary artery disease (CAD) and to validate the clinical significance. Bronchial arteries 10-15 mm long were obtained from 40 patients with a mean age of 62.3 years who underwent major thoracic procedures. Their medical history and detailed clinical and laboratory arteriosclerotic risk factors were documented. The mean diameter of bronchial artery specimens was 0.97 mm. Histology revealed medial calcific sclerosis only in 1 patient (2.5%) without simultaneous, established atherosclerotic lesions or narrowing of the lumen. Furthermore, the vessel diameter was significantly correlated not only with the advanced stage of the disease (p = 0.031), but also with the proximal occlusion of the bronchial tree (p = 0.042). We noted a marginally not significant correlation between arteriosclerosis and metabolic syndrome (p = 0.075), independent from a history of CAD (p = 0.84). Bronchial arteries exhibit only medial calcific sclerosis. CAD and chronic obstructive pulmonary disease do not seem to affect them in terms of atherosclerotic alteration findings or vessel diameter changes. The bronchial resistance to arteriosclerosis might support the mediastinal status quo through their anastomoses, contributing to all its structures, and might be indirect evidence of a different physiological function of the bronchial endothelium, which needs to be further investigated. Copyright 2009 S. Karger AG, Basel.

  8. Intestine of dystrophic mice presents enhanced contractile resistance to stretching despite morphological impairment

    OpenAIRE

    Alves, Gabriel A. [UNIFESP; Silva, Luisa R. [UNIFESP; Rosa, Eloi F. [UNIFESP; Aboulafia, Jeannine [UNIFESP; Freymueller-Haapalainen, Edna [UNIFESP; Souccar, Caden [UNIFESP; Nouailhetas, Viviane L. A. [UNIFESP

    2014-01-01

    Protein dystrophin is a component of the dystrophin-associated protein complex, which links the contractile machinery to the plasma membrane and to the extra-cellular matrix. Its absence leads to a condition known as Duchenne muscular dystrophy (DMD), a disease characterized by progressive skeletal muscle degeneration, motor disability, and early death. in mdx mice, the most common DMD animal model, loss of muscle cells is observed, but the overall disease alterations are less intense than in...

  9. Vascular narrowing in pulmonary arterial hypertension is heterogeneous: rethinking resistance

    NARCIS (Netherlands)

    Rol, N.; Timmer, E.M.; Faes, T.J.; Noordegraaf, A.V.; Grunberg, K.; Bogaard, H.J.; Westerhof, N.

    2017-01-01

    In idiopathic pulmonary arterial hypertension (PAH), increased pulmonary vascular resistance is associated with structural narrowing of small (resistance) vessels and increased vascular tone. Current information on pulmonary vascular remodeling is mostly limited to averaged increases in wall

  10. Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats

    International Nuclear Information System (INIS)

    Ribeiro Júnior, Rogério Faustino; Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa; Araújo, Julia F.P. de; Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim; Graceli, Jones B.; Stefanon, Ivanita

    2016-01-01

    Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration–response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT 1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O 2 − production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. - Highlights: • Tributyltin chloride reduces estrogen levels in female rats. • Treatment with TBT

  11. Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Rui-Xing Wang

    2015-03-01

    Full Text Available Background: Pulmonary hypertension (PH is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1 induced contraction of pulmonary arteries (PAs and store-operated Ca2+ entry (SOCE in pulmonary arterial smooth muscle cells (PASMCs from chronic hypoxia (CH and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH.

  12. Anomalous renal artery is potential cause of resistant hypertension ...

    African Journals Online (AJOL)

    Background: Drug-resistant hypertension can be attributable to secondary hypertension and other causes. Anomalous renal artery is uncommon but can be a potential cause of resistant hypertension. Case Report: We highlight the challenges in management of resistant hypertension and describe its unusual association ...

  13. Obesity Resistance Promotes Mild Contractile Dysfunction Associated with Intracellular Ca{sup 2+} Handling

    Energy Technology Data Exchange (ETDEWEB)

    Sá, Felipe Gonçalves dos Santos de; Lima-Leopoldo, Ana Paula; Jacobsen, Bruno Barcellos; Ferron, Artur Junio Togneri; Estevam, Wagner Muller [Centro de Educação Física e Desportos - Departamento de Desportos - Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Campos, Dijon Henrique Salomé [Departamento de Clínica Médica - Faculdade de Medicina - Universidade Estadual Paulista, Botucatu, São Paulo (Brazil); Castardeli, Edson; Cunha, Márcia Regina Holanda da [Centro de Educação Física e Desportos - Departamento de Desportos - Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Cicogna, Antonio Carlos [Departamento de Clínica Médica - Faculdade de Medicina - Universidade Estadual Paulista, Botucatu, São Paulo (Brazil); Leopoldo, André Soares, E-mail: andresoaresleopoldo@gmail.com [Centro de Educação Física e Desportos - Departamento de Desportos - Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

    2015-12-15

    Diet-induced obesity is frequently used to demonstrate cardiac dysfunction. However, some rats, like humans, are susceptible to developing an obesity phenotype, whereas others are resistant to that. To evaluate the association between obesity resistance and cardiac function, and the impact of obesity resistance on calcium handling. Thirty-day-old male Wistar rats were distributed into two groups, each with 54 animals: control (C; standard diet) and obese (four palatable high-fat diets) for 15 weeks. After the experimental protocol, rats consuming the high-fat diets were classified according to the adiposity index and subdivided into obesity-prone (OP) and obesity-resistant (OR). Nutritional profile, comorbidities, and cardiac remodeling were evaluated. Cardiac function was assessed by papillary muscle evaluation at baseline and after inotropic maneuvers. The high-fat diets promoted increase in body fat and adiposity index in OP rats compared with C and OR rats. Glucose, lipid, and blood pressure profiles remained unchanged in OR rats. In addition, the total heart weight and the weight of the left and right ventricles in OR rats were lower than those in OP rats, but similar to those in C rats. Baseline cardiac muscle data were similar in all rats, but myocardial responsiveness to a post-rest contraction stimulus was compromised in OP and OR rats compared with C rats. Obesity resistance promoted specific changes in the contraction phase without changes in the relaxation phase. This mild abnormality may be related to intracellular Ca2+ handling.

  14. Obesity Resistance Promotes Mild Contractile Dysfunction Associated with Intracellular Ca2+ Handling

    International Nuclear Information System (INIS)

    Sá, Felipe Gonçalves dos Santos de; Lima-Leopoldo, Ana Paula; Jacobsen, Bruno Barcellos; Ferron, Artur Junio Togneri; Estevam, Wagner Muller; Campos, Dijon Henrique Salomé; Castardeli, Edson; Cunha, Márcia Regina Holanda da; Cicogna, Antonio Carlos; Leopoldo, André Soares

    2015-01-01

    Diet-induced obesity is frequently used to demonstrate cardiac dysfunction. However, some rats, like humans, are susceptible to developing an obesity phenotype, whereas others are resistant to that. To evaluate the association between obesity resistance and cardiac function, and the impact of obesity resistance on calcium handling. Thirty-day-old male Wistar rats were distributed into two groups, each with 54 animals: control (C; standard diet) and obese (four palatable high-fat diets) for 15 weeks. After the experimental protocol, rats consuming the high-fat diets were classified according to the adiposity index and subdivided into obesity-prone (OP) and obesity-resistant (OR). Nutritional profile, comorbidities, and cardiac remodeling were evaluated. Cardiac function was assessed by papillary muscle evaluation at baseline and after inotropic maneuvers. The high-fat diets promoted increase in body fat and adiposity index in OP rats compared with C and OR rats. Glucose, lipid, and blood pressure profiles remained unchanged in OR rats. In addition, the total heart weight and the weight of the left and right ventricles in OR rats were lower than those in OP rats, but similar to those in C rats. Baseline cardiac muscle data were similar in all rats, but myocardial responsiveness to a post-rest contraction stimulus was compromised in OP and OR rats compared with C rats. Obesity resistance promoted specific changes in the contraction phase without changes in the relaxation phase. This mild abnormality may be related to intracellular Ca2+ handling

  15. Proteomic analysis of vascular smooth muscle cells in physiological condition and in pulmonary arterial hypertension: Toward contractile versus synthetic phenotypes.

    Science.gov (United States)

    Régent, Alexis; Ly, Kim Heang; Lofek, Sébastien; Clary, Guilhem; Tamby, Mathieu; Tamas, Nicolas; Federici, Christian; Broussard, Cédric; Chafey, Philippe; Liaudet-Coopman, Emmanuelle; Humbert, Marc; Perros, Frédéric; Mouthon, Luc

    2016-10-01

    Vascular smooth muscle cells (VSMCs) are highly specialized cells that regulate vascular tone and participate in vessel remodeling in physiological and pathological conditions. It is unclear why certain vascular pathologies involve one type of vessel and spare others. Our objective was to compare the proteomes of normal human VSMC from aorta (human aortic smooth muscle cells, HAoSMC), umbilical artery (human umbilical artery smooth muscle cells, HUASMC), pulmonary artery (HPASMC), or pulmonary artery VSMC from patients with pulmonary arterial hypertension (PAH-SMC). Proteomes of VSMC were compared by 2D DIGE and MS. Only 19 proteins were differentially expressed between HAoSMC and HPASMC while 132 and 124 were differentially expressed between HUASMC and HAoSMC or HPASMC, respectively (fold change 1.5≤ or -1.5≥, p < 0.05). As much as 336 proteins were differentially expressed between HPASMC and PAH-SMC (fold change 1.5≤ or -1.5≥, p < 0.05). HUASMC expressed increased amount of α-smooth muscle actin compared to either HPASMC or HAoSMC (although not statistically significant). In addition, PAH-SMC expressed decreased amount of smooth muscle myosin heavy chain and proliferation rate was increased compared to HPASMC thus supporting that PAH-SMC have a more synthetic phenotype. Analysis with Ingenuity identified paxillin and (embryonic lethal, abnormal vision, drosophila) like 1 (ELAVL1) as molecules linked with a lot of proteins differentially expressed between HPASMC and PAH-SMC. There was a trend toward reduced proliferation of PAH-SMC with paxillin-si-RNA and increased proliferation with ELAVL1-siRNA. Thus, VSMCs have very diverse protein content depending on their origin and this is in link with phenotypic differentiation. Paxillin targeting may be a promising treatment of PAH. ELAVL1 also participate in the regulation of PAH-SMC proliferation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Alteration in contractile G-protein coupled receptor expression by moist snuff and nicotine in rat cerebral arteries

    DEFF Research Database (Denmark)

    Sandhu, Hardip; Xu, Cang-Bao; Edvinsson, Lars

    2011-01-01

    nicotine/ml) lowered the 5-HT(1B) receptor-mediated contraction. Furthermore, DSS shifted the TP receptor-mediated contraction curve left-wards with a stronger contraction. High dose of nicotine (250ng nicotine/ml) increased the ET(B) receptor-mediated contraction. The combined 5-HT(1B) and 5-HT(2A...... was kept at plasma level of snus users (25ng nicotine/ml). A high dose (250ng nicotine/ml) was also included due to the previous results showing alteration in the GPCR expression by nicotine at this concentration. Contractile responses to the ET(B) receptor agonist sarafotoxin 6c, 5-HT(1B) receptor agonist...... 5-carboxamidotryptamine, and TP receptor agonist U46619 were investigated by a sensitive myograph. The expression of ET(B), 5-HT(1B), and TP receptors was studied at mRNA and protein levels using quantitative real-time PCR and immunohistochemistry, respectively. Organ culture with WSS or DSS (25ng...

  17. Insulin resistance and associated dysfunction of resistance vessels and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2005-01-01

    vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counterregulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin...

  18. Alteration in contractile G-protein coupled receptor expression by moist snuff and nicotine in rat cerebral arteries

    DEFF Research Database (Denmark)

    Sandhu, Hardip; Xu, Cang-Bao; Edvinsson, Lars

    2011-01-01

    The cardiovascular risk for users of use of Swedish snus/American snuff (moist tobacco) has been debated for a long time. The present study was designed to examine the effects of water- or lipid-soluble (DMSO-soluble) snus and nicotine, the most important substance in tobacco, on the expression...... of vasocontractile G-protein coupled receptors (GPCR), such as endothelin ET(B), serotonin 5-HT(1B), and thromboxane A(2) TP receptors, in rat cerebral arteries. Studies show that these vasocontractile GPCR show alterations by lipid-soluble cigarette smoke particles via activation of mitogen-activated protein...... kinases (MAPK). However, the effects of moist tobacco on the expression of GPCR are less studied. Rat middle cerebral arteries were isolated and organ cultured in serum-free medium for 24h in the presence of water-soluble snus (WSS), DMSO-soluble snus (DSS), or nicotine. The dose of snus and nicotine...

  19. Soybean oil increases SERCA2a expression and left ventricular contractility in rats without change in arterial blood pressure

    Directory of Open Access Journals (Sweden)

    Vassallo Dalton

    2010-05-01

    Full Text Available Abstract Background Our aim was to evaluate the effects of soybean oil treatment for 15 days on arterial and ventricular pressure, myocardial mechanics and proteins involved in calcium handling. Methods Wistar rats were divided in two groups receiving 100 μL of soybean oil (SB or saline (CT i.m. for 15 days. Ventricular performance was analyzed in male 12-weeks old Wistar rats by measuring left ventricle diastolic and systolic pressure in isolated perfused hearts according to the Langendorff technique. Protein expression was measured by Western blot analysis. Results Systolic and diastolic arterial pressures did not differ between CT and SB rats. However, heart rate was reduced in the SB group. In the perfused hearts, left ventricular isovolumetric systolic pressure was higher in the SB hearts. The inotropic response to extracellular Ca2+ and isoproterenol was higher in the soybean-treated animals than in the control group. Myosin ATPase and Na+-K+ATPase activities, the expression of sarcoplasmic reticulum calcium pump (SERCA2a and sodium calcium exchanger (NCX were increased in the SB group. Although the phosfolamban (PLB expression did not change, its phosphorylation at Ser16 was reduced while the SERCA2a/PLB ratio was increased. Conclusions In summary, soybean treatment for 15 days in rats increases the left ventricular performance without affecting arterial blood pressure. These changes might be associated with an increase in the myosin ATPase activity and SERCA2a expression.

  20. Evidence for a non-adrenoceptor, imidazoline-mediated contractile response to oxymetazoline in the porcine isolated rectal artery.

    Science.gov (United States)

    Minyan, W; Dunn, W R; Blaylock, N A; Chan, S L; Wilson, V G

    2001-04-01

    Imidazoline derivatives are known to elicit responses through both alpha(2)-adrenoceptor and non-adrenoceptor, imidazoline sites, though as yet there are no examples of the latter on vascular smooth muscle. In the presence of 0.3 microM prazosin, neither UK-14304 (0.01 - 3 microM) nor oxymetazoline (0.01 - 30 microM) caused a significant contraction of the porcine isolated rectal artery, a preparation with a low density of alpha(2)-adrenoceptors. In the presence of a combination of U46619 and forskolin, however, both agonists produced concentration-dependent contractions. Pretreatment with phenoxybenzamine (3 microM) abolished responses to UK-14304, but left those elicited by oxymetazoline largely unaffected. The putative I(3) imidazoline antagonist 2-(2,3 dihydro-2-benzofuranyl)-2-imidazole (KU-14R, 10 microM) caused a 6 fold rightward displacement of the phenoxybenzamine-insensitive concentration - response curve to oxymetazoline. Our data indicates that non-adrenoceptor, imidazoline sites, pharmacologically similar to the I(3) imidazoline site on islet cells, mediate vasoconstriction in the porcine isolated rectal artery.

  1. Stimulation of the cardiopulmonary baroreflex enhances ventricular contractility in awake dogs: a mathematical analysis study.

    Science.gov (United States)

    Sala-Mercado, Javier A; Moslehpour, Mohsen; Hammond, Robert L; Ichinose, Masashi; Chen, Xiaoxiao; Evan, Sell; O'Leary, Donal S; Mukkamala, Ramakrishna

    2014-08-15

    The cardiopulmonary baroreflex responds to an increase in central venous pressure (CVP) by decreasing total peripheral resistance and increasing heart rate (HR) in dogs. However, the direction of ventricular contractility change is not well understood. The aim was to elucidate the cardiopulmonary baroreflex control of ventricular contractility during normal physiological conditions via a mathematical analysis. Spontaneous beat-to-beat fluctuations in maximal ventricular elastance (Emax), which is perhaps the best available index of ventricular contractility, CVP, arterial blood pressure (ABP), and HR were measured from awake dogs at rest before and after β-adrenergic receptor blockade. An autoregressive exogenous input model was employed to jointly identify the three causal transfer functions relating beat-to-beat fluctuations in CVP to Emax (CVP → Emax), which characterizes the cardiopulmonary baroreflex control of ventricular contractility, ABP to Emax, which characterizes the arterial baroreflex control of ventricular contractility, and HR to Emax, which characterizes the force-frequency relation. The CVP → Emax transfer function showed a static gain of 0.037 ± 0.010 ml(-1) (different from zero; P baroreflex. Following β-adrenergic receptor blockade, the CVP → Emax transfer function showed a static gain of 0.0007 ± 0.0113 ml(-1) (different from control; P baroreflex increases ventricular contractility through β-adrenergic receptor system mediation. Copyright © 2014 the American Physiological Society.

  2. [Resistant arterial hypertension and coarctation of the aorta].

    Science.gov (United States)

    Martínez-Quintana, Efrén; Rossique-Delmas, Pilar; Rodríguez-González, Fayna

    2014-01-01

    Coarctation of the aorta accounts for around 5 percent of all congenital heart defects. Many of these patients develop arterial hypertension, and occasionally resistant arterial hypertension, despite adequate correction. This may lead to potentially fatal complications such as heart failure, aortic dissection, cerebrovascular events, or myocardial infarction. Therefore, a correct diagnosis must be made and an appropriate treatment started to reduce arterial hypertension, arteriosclerotic vascular disease, as well as the increased risk of cardiovascular morbidity and mortality. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  3. Comparative effects of mibefradil and other calcium antagonists on resistance arteries of different end organs

    NARCIS (Netherlands)

    van der Lee, R.; Pfaffendorf, M.; van Zwieten, P. A.

    1999-01-01

    The biphasic contractile responses of rat isolated mesenteric, renal, coronary and basilar small arteries to potassium-induced depolarization were investigated. The tonic phase is assumed to be exclusively the result of L-type calcium channel (LCC) activation, whereas in the generation of the phasic

  4. Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats.

    Science.gov (United States)

    Ribeiro Júnior, Rogério Faustino; Marques, Vinicius Bermond; Nunes, Dieli Oliveira; Ronconi, Karoline de Sousa; de Araújo, Julia F P; Rodrigues, Paula Lopes; Padilha, Alessandra Simão; Vassallo, Dalton Valentim; Graceli, Jones B; Stefanon, Ivanita

    2016-03-15

    Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration-response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O2(-) production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Prostaglandin I2 and Prostaglandin E2 Modulate Human Intrarenal Artery Contractility Through Prostaglandin E2-EP4, Prostacyclin-IP, and Thromboxane A2-TP Receptors

    DEFF Research Database (Denmark)

    Eskildsen, Morten P; Hansen, Pernille B L; Stubbe, Jane

    2014-01-01

    . In conclusion, PGE2 and PGI2 may protect renal perfusion by activating cognate IP and EP4 receptors associated with smooth muscle cells and endothelium in human intrarenal arteries and contribute to increased renal vascular resistance at high pathological concentrations mediated by noncognate TP receptor.......Cyclooxygenase inhibitors decrease renal blood flow in settings with decreased effective circulating volume. The present study examined the hypothesis that prostaglandins, prostaglandin E2 (PGE2) and prostacyclin (PGI2), induce relaxation of human intrarenal arteries through PGE2-EP and PGI2-IP...... and PGI2 induced concentration-dependent relaxation (-log EC50: PGE2=7.1±0.3 and PGI2=7.7). The response to PGE2 displayed endothelium dependence and desensitization. Relaxation by PGE2 was mimicked by an EP4 receptor agonist (CAY10598, EC50=6.7±0.2). The relaxation after PGI2 was abolished by an IP...

  6. Pulmonary arterial dysfunction in insulin resistant obese Zucker rats

    Directory of Open Access Journals (Sweden)

    Cogolludo Angel

    2011-04-01

    Full Text Available Abstract Background Insulin resistance and obesity are strongly associated with systemic cardiovascular diseases. Recent reports have also suggested a link between insulin resistance with pulmonary arterial hypertension. The aim of this study was to analyze pulmonary vascular function in the insulin resistant obese Zucker rat. Methods Large and small pulmonary arteries from obese Zucker rat and their lean counterparts were mounted for isometric tension recording. mRNA and protein expression was measured by RT-PCR or Western blot, respectively. KV currents were recorded in isolated pulmonary artery smooth muscle cells using the patch clamp technique. Results Right ventricular wall thickness was similar in obese and lean Zucker rats. Lung BMPR2, KV1.5 and 5-HT2A receptor mRNA and protein expression and KV current density were also similar in the two rat strains. In conductance and resistance pulmonary arteries, the similar relaxant responses to acetylcholine and nitroprusside and unchanged lung eNOS expression revealed a preserved endothelial function. However, in resistance (but not in conductance pulmonary arteries from obese rats a reduced response to several vasoconstrictor agents (hypoxia, phenylephrine and 5-HT was observed. The hyporesponsiveness to vasoconstrictors was reversed by L-NAME and prevented by the iNOS inhibitor 1400W. Conclusions In contrast to rat models of type 1 diabetes or other mice models of insulin resistance, the obese Zucker rats did not show any of the characteristic features of pulmonary hypertension but rather a reduced vasoconstrictor response which could be prevented by inhibition of iNOS.

  7. Relationship of Physical Function to Single Muscle Fiber Contractility in Older Adults: Effects of Resistance Training with and without Caloric Restriction.

    Science.gov (United States)

    Wang, Zhong-Min; Leng, Xiaoyan; Messi, María Laura; Choi, Seung J; Marsh, Anthony P; Nicklas, Barbara; Delbono, Osvaldo

    2018-03-13

    Previous studies support beneficial effects of both resistance exercise training (RT) and caloric restriction (CR) on skeletal muscle strength and physical performance. The goal of this study was to determine the effects of adding CR to RT on single-muscle fiber contractility responses to RT in older overweight and obese adults. We analyzed contractile properties in 1,253 single myofiber from muscle biopsies of the vastus lateralis, as well as physical performance and thigh muscle volume, in 31 older (65-80 yrs), overweight or obese (body mass index= 27-35 kg/m2) men (n=19) and women (n=12) who were randomly assigned to a standardized, progressive RT intervention with CR (RT+CR; n=15) or without CR (RT; n=16) for 5 months. Both interventions evoked an increase in force normalized to CSA, in type-I and type-II fibers and knee extensor quality. However, these improvements were not different between intervention groups. In the RT group, changes in total thigh fat volume inversely correlated with changes in type-II fiber force (r = -0.691; p=0.019). Within the RT+CR group, changes in gait speed correlated positively with changes in type-I fiber CSA (r=0.561; p=0.030). In addition, increases in type-I normalized fiber force were related to decreases in thigh intermuscular fat volume (r= -0.539; p= 0.038). Single muscle fiber force and knee extensor quality improve with RT and RT+CR; however, CR does not enhance improvements in single muscle fiber contractility or whole muscle in response to RT in older overweight and obese men and women.

  8. Unravelling detrusor underactivity: Development of a bladder outlet resistance-Bladder contractility nomogram for adult male patients with lower urinary tract symptoms.

    Science.gov (United States)

    Oelke, Matthias; Rademakers, Kevin L J; van Koeveringe, Gommert A

    2016-11-01

    Voiding dysfunction in adult men may be caused by bladder outlet obstruction (BOO) and/or detrusor underactivity (DU). Until now, it is only possible to classify BOO and DU by pressure-flow analysis. Low values of the maximum Watts factor (W max ) indicate DU but thresholds for the diagnosis have not been established. Purpose of this study was to construct a nomogram using bladder outlet resistance and detrusor contractility in order to classify BOO and DU simultaneously. Treatment naïve men aged ≥40 years with uncomplicated lower urinary tract symptoms (LUTS) were prospectively evaluated. Patients were assessed with IPSS, prostate volume, uroflowmetry, post-void residual, and pressure-flow measurement. The bladder outlet obstruction index (BOOI) was used to determine BOO-grade and W max to calculate detrusor contractility. Individual BOOI-W max values were plotted in a graph. Linear interpolation was applied to determine the 10th, 25th, 50th, 75th, and 90th percentiles. Retrospective analysis of 822 male patients with means of 64 years, IPSS 16, and prostate volume of 40 cc. Patient and clinical parameters of the <25th percentile groups were significantly different compared to the 25th-50th percentiles: age (66 vs. 63 years, P = 0.006), bladder capacity (503 vs. 442 ml, P = 0.009), post-void residual urine (167 vs. 116 ml, P = 0.001), and voiding efficiency (67% vs. 73%, P = 0.015). The nomogram quantifies the relationship between detrusor contractility and BOO in men with LUTS. A measurement value <25th percentile correlates with clinical indicators of DU and is proposed as a cut-off value for DU-diagnosis. Higher age, bladder capacity, and PVR as well as lower voiding efficiency indicate DU. Neurourol. Urodynam. 35:980-986, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  9. Structural abnormalities of small resistance arteries in essential hypertension.

    Science.gov (United States)

    Rizzoni, Damiano; Agabiti-Rosei, Enrico

    2012-06-01

    Regardless of the mechanisms that initiate the increase in blood pressure, the development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, the small arteries smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, while in some secondary forms of hypertension, a hypertrophic remodeling may be detected. Also, in non-insulin-dependent diabetes mellitus, a hypertrophic remodeling of subcutaneous small arteries is present. The results from our own group have suggested that indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive patients, over and above all other known cardiovascular risk factors. Therefore, the regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effect on vascular structure, both in human and in animal models of genetic and experimental hypertension. A complete normalization of small resistance artery structure is demonstrated in hypertensive patients, after long-term and effective therapy with ACE inhibitors, angiotensin II receptor blockers and calcium antagonists. Few data are available in diabetic hypertensive patients; however, blockade of the renin-angiotensin system seems to be effective in this regard. In conclusion, there are several pieces of evidence that suggest that small resistance artery structure may be considered an intermediate endpoint in the evaluation of the effects of antihypertensive therapy; however, there are presently no data available about the prognostic impact of the regression of vascular structural alterations in hypertension and diabetes.

  10. Four weeks of high- versus low-load resistance training to failure on the rate of torque development, electromechanical delay, and contractile twitch properties.

    Science.gov (United States)

    Jenkins, N Dm; Housh, T J; Buckner, S L; Bergstrom, H C; Smith, C M; Cochrane, K C; Hill, E C; Miramonti, A A; Schmidt, R J; Johnson, G O; Cramer, J T

    2016-06-01

    The purpose of this study was to investigate the effects of 4-weeks of high- versus low-load resistance training to failure on rate of torque development (RTD), electromechanical delay (EMD), and contractile twitch characteristics. Fifteen men (mean±SD; age=21.7±2.4 yrs) were randomly assigned to either a high- (80% 1RM; n=7) or low-load (30% 1RM; n=8) training group and completed elbow flexion resistance training to failure 3 times per week for 4 weeks. The participants were tested at baseline, 2-, and 4-weeks of training. Peak RTD (pRTDV) and RTD at 0-30 (RTD30V), 0-50 (RTD50V), 0-100 (RTD100V), and 0-200 (RTD200V) ms, integrated EMG amplitude (iEMG) at 0-30, 0-50, and 0-100 ms, and EMD were quantified during maximal voluntary isometric muscle actions. Peak twitch torque, peak RTD, time to peak twitch, 1/2 relaxation time and the peak relaxation rate were quantified during evoked twitches. Four weeks of high-load, but not low-load resistance training, increased RTD200V. There were also increases in iEMG during the first 30 ms of muscle activation for the high- and low-load groups, which may have indirectly indicated increases in early phase motor unit recruitment and/or firing frequency. There were no significant training-induced adaptations in EMD or contractile twitch properties.

  11. Review of aspirin and clopidogrel resistance in peripheral arterial disease.

    Science.gov (United States)

    Guirgis, Mina; Thompson, Peter; Jansen, Shirley

    2017-11-01

    Aspirin resistance (AR) and clopidogrel resistance (CR) are terms used to describe a reduction in the medication's efficacy in inhibiting platelet aggregation despite regular dosing. This review gives context to the clinical role and implications of antiplatelet resistance in peripheral arterial disease (PAD). A review of English-language literature on AR and CR in PAD involving human subjects using PubMed and MEDLINE databases was performed in April 2017. A total of 2075 patients in 22 relevant studies were identified. To give this issue context, a review of the larger, more established literature on antiplatelet resistance in coronary disease was undertaken, identifying significant research associating resistance to major adverse cardiovascular events (MACEs). Studies in the coronary arterial disease literature have strongly associated antiplatelet resistance with increased MACE. Prevalence of AR or CR in coronary disease appears to be >55% for each in some studies. Meta-analyses of >50 studies revealed that AR and CR are significantly associated with MACE (relative risk of 2.09 and 2.8, respectively). This adds further weight to the literature reporting antiplatelet resistance as an independent predictor of and a threefold risk factor for major adverse cardiovascular events. The prevalence of resistance in PAD in this review was comparable to that in the coronary disease literature, with AR and CR prevalence up to 60% and 65%, respectively. There is evidence that the adverse effects of antiplatelet resistance are significant in PAD. In fact, research directly studying stent thrombosis populations with either coronary arterial disease or PAD revealed more significantly impaired platelet responsiveness to clopidogrel and aspirin in PAD compared with similar individuals with coronary disease. AR in PAD was found in studies to be a significant risk factor for iliofemoral stent reocclusion (P = .0093) and stroke in patients with symptomatic carotid disease (P

  12. Permanent Distal Occlusion of Middle Cerebral Artery in Rat Causes Local Increased ETB, 5-HT1B and AT1 Receptor-Mediated Contractility Downstream of Occlusion

    DEFF Research Database (Denmark)

    Rasmussen, Marianne N P; Hornbak, Malene; Larsen, Stine S

    2013-01-01

    Background/Aims: In response to experimental stroke, a characteristic functional and expressional upregulation of contractile G-protein-coupled receptors has been uncovered in the affected cerebral vasculature; however, the mechanism initiating this phenomenon remains unknown. Methods: Using a mo...

  13. Effect of whole body resistance training on arterial compliance in young men.

    NARCIS (Netherlands)

    Rakobowchuk, M.; McGowan, C.L.; Groot, P.C.E. de; Bruinsma, D.; Hartman, J.W.; Phillips, S.M.; MacDonald, M.J.

    2005-01-01

    The effect of resistance training on arterial stiffening is controversial. We tested the hypothesis that resistance training would not alter central arterial compliance. Young healthy men (age, 23 +/- 3.9 (mean +/- s.e.m.) years; n = 28,) were whole-body resistance trained five times a week for 12

  14. Acute Carotid Artery Stent Thrombosis Due to Dual Antiplatelet Resistance

    International Nuclear Information System (INIS)

    Köklü, Erkan; Arslan, Şakir; Yüksel, İsa Öner; Bayar, Nermin; Koç, Pınar

    2015-01-01

    Carotid artery stenting (CAS) is a revascularization modality that is an alternative to carotid endarterectomy. The efficacy of CAS in primary and secondary prevention from ischemic stroke has been demonstrated in various trials. Acute thrombosis of CAS is a rare complication that can lead to dramatic and catastrophic consequences. We discuss a case of acute CAS thrombosis in a patient who had previously undergone successful CAS. CAS was performed in a 73-year-old man who had had dysarthria lasting 2 weeks with 95 % stenosis in his left internal carotid artery. An acute cerebrovascular event resulting in right-sided hemiplegia developed 24 h after the procedure. Computed tomographic carotid angiography revealed complete occlusion of the stent with thrombus. The cause of stent thrombosis was thought to be antiaggregant resistance to both acetylsalicylic acid and clopidogrel. The most important cause of acute CAS thrombosis is inadequate or ineffective antiaggregant therapy. Evaluating patients who are candidates for CAS for acetylsalicylic acid and clopidogrel resistance may preclude this complication

  15. Acute Carotid Artery Stent Thrombosis Due to Dual Antiplatelet Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Köklü, Erkan, E-mail: drerkankoklu@gmail.com; Arslan, Şakir; Yüksel, İsa Öner; Bayar, Nermin [Antalya Education and Research Hospital, Clinic of Cardiology (Turkey); Koç, Pınar [Antalya Education and Research Hospital, Clinic of Radiology (Turkey)

    2015-08-15

    Carotid artery stenting (CAS) is a revascularization modality that is an alternative to carotid endarterectomy. The efficacy of CAS in primary and secondary prevention from ischemic stroke has been demonstrated in various trials. Acute thrombosis of CAS is a rare complication that can lead to dramatic and catastrophic consequences. We discuss a case of acute CAS thrombosis in a patient who had previously undergone successful CAS. CAS was performed in a 73-year-old man who had had dysarthria lasting 2 weeks with 95 % stenosis in his left internal carotid artery. An acute cerebrovascular event resulting in right-sided hemiplegia developed 24 h after the procedure. Computed tomographic carotid angiography revealed complete occlusion of the stent with thrombus. The cause of stent thrombosis was thought to be antiaggregant resistance to both acetylsalicylic acid and clopidogrel. The most important cause of acute CAS thrombosis is inadequate or ineffective antiaggregant therapy. Evaluating patients who are candidates for CAS for acetylsalicylic acid and clopidogrel resistance may preclude this complication.

  16. Elastin organization in pig and cardiovascular disease patients' pericardial resistance arteries

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Leurgans, Thomas; Nissen, Inger

    2015-01-01

    Peripheral vascular resistance is increased in essential hypertension. This involves structural changes of resistance arteries and stiffening of the arterial wall, including remodeling of the extracellular matrix. We hypothesized that biopsies of the human parietal pericardium, obtained during...... coronary artery bypass grafting or cardiac valve replacement surgeries, can serve as a source of resistance arteries for structural research in cardiovascular disease patients. We applied two-photon excitation fluorescence microscopy to study the parietal pericardium and isolated pericardial resistance...... arteries with a focus on the collagen and elastin components of the extracellular matrix. Initial findings in pig tissue were confirmed in patient biopsies. The microarchitecture of the internal elastic lamina in both the pig and patient pericardial resistance arteries (studied at a transmural pressure...

  17. Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries.

    Directory of Open Access Journals (Sweden)

    Sonya Hui

    Full Text Available We recently identified sphingosine-1-phosphate (S1P signaling and the cystic fibrosis transmembrane conductance regulator (CFTR as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i express critical S1P signaling elements, (ii constrict in response to S1P and (iii lose myogenic responsiveness following S1P receptor antagonism (JTE013. However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.

  18. Coffee, nutritional status, and renal artery resistive index.

    Science.gov (United States)

    Trovato, Guglielmo M; Pirri, Clara; Martines, Giuseppe Fabio; Trovato, Francesca; Catalano, Daniela

    2010-01-01

    The relationship between nutrition and atherosclerosis is known, even dissociated from protein malnutrition. Cardiovascular impact of several nutrients is known; among them the action of coffee is still debated and cardiovascular effect of caffeine has been investigated without definite results. The aim of this study is to investigate whether coffee habits, and/or quantity of coffee consumption, have any relationship with renal resistive index (RRI), a hallmark of arterial stiffness (AS). The relationship of AS with nutritional status assessed by body composition and serum albumin, insulin resistance (assessed by HOMA), and renal function assessed by glomerular filtration rate (GFR) is concurrently investigated. This study was done with 221 consecutive patients, without diabetes, cancer, liver, renal, and heart disease, referred for clinical noninvasive assessment and nutritional counseling: 124 essential hypertensive and 97 nonhypertensive patients were eligible. Personalized Mediterranean diet, physical activity increase, and smoking withdrawal counseling were provided. By multiple linear regression, fat-free mass (FFM), HOMA (positive relationship), and number of cups of coffee/day (negative relationship) account for 17.2% of the variance to RRI. By odds ratios lower risk to increased RRI is associated with higher serum albumin, higher hemoglobin, and FFM; greater risk is associated with hypertension, insulin resistance (HOMA ≥ 3.0), and renal insufficiency (GFR ≤ 90); coffee, assessed by number of cups/day, reduces risk. Coffee use is inversely associated with RRI. Habitual coffee users have risk protection to higher RRI; lower serum albumin, insulin resistance, and renal insufficiency are associated with greater RRI.

  19. Upregulation of contractile endothelin type B receptors by lipid-soluble cigarette smoking particles in rat cerebral arteries via activation of MAPK

    DEFF Research Database (Denmark)

    Sandhu, Hardip; Xu, Cang Bao; Edvinsson, Lars

    2010-01-01

    Cigarette smoke exposure increases the risk of stroke. However, the underlying molecular mechanisms are poorly understood. Endothelin system plays key roles in the pathogenesis of stroke. The present study was designed to examine if lipid-soluble (dimethyl sulfoxide-soluble) cigarette smoke...... or water-soluble cigarette smoke particles to the organ culture. The increased upregulation of contractile ET(B) receptors by DSP was abrogated by U0126, SP600125, actinomycin D, and cycloheximide, suggesting that the underlying molecular mechanisms involved in this process include activation of MEK...

  20. LPS from Porphyromonas gingivalis increases the sensitivity of contractile response mediated by endothelin-B (ET(B)) receptors in cultured endothelium-intact rat coronary arteries

    DEFF Research Database (Denmark)

    Ghorbani, Bahareh; Holmstrup, Palle; Edvinsson, Lars

    2010-01-01

    The purpose of our study was to examine if lipopolysaccharide (LPS) from Porphyromonas gingivalis (P.g.) modifies the vasomotor responses to Endothelin-1 (ET-1) and Sarafotoxin 6c (S6c) in rat coronary arteries. The arteries were studied directly or following organ culture for 24h in absence...

  1. The renal arterial resistive index and stage of chronic kidney disease in patients with renal allograft

    DEFF Research Database (Denmark)

    Winther, Stine O; Thiesson, Helle C; Poulsen, Lene N

    2012-01-01

    The study investigated the optimal threshold value of renal arterial resistive index as assessed by Doppler ultrasonography determining chronic kidney disease stage 4 or higher in patients with renal allograft.......The study investigated the optimal threshold value of renal arterial resistive index as assessed by Doppler ultrasonography determining chronic kidney disease stage 4 or higher in patients with renal allograft....

  2. Aluminum exposure for one hour decreases vascular reactivity in conductance and resistance arteries in rats

    International Nuclear Information System (INIS)

    Schmidt, Patrícia Medeiros; Escobar, Alyne Goulart; Torres, João Guilherme Dini; Martinez, Caroline Silveira; Rizzetti, Danize Aparecida; Kunz, Simone Noremberg; Vassallo, Dalton Valentim; Alonso, María Jesús; Peçanha, Franck Maciel; Wiggers, Giulia Alessandra

    2016-01-01

    Aims: Aluminum (Al) is an important environmental contaminant; however, there are not enough evidences of Al-induced cardiovascular dysfunction. We investigated the effects of acute exposure to aluminum chloride (AlCl 3 ) on blood pressure, vascular reactivity and oxidative stress. Methods and results: Male Wistar rats were divided into two groups: Untreated: vehicle (ultrapure water, ip) and AlCl 3 : single dose of AlCl 3 (100 mg/kg,ip). Concentration-response curves to phenylephrine in the absence and presence of endothelium, the nitric oxide synthase inhibitor L-NAME, the potassium channel blocker tetraethylammonium, and the NADPH oxidase inhibitor apocynin were performed in segments from aortic and mesenteric resistance arteries. NO released was assessed in aorta and reactive oxygen species (ROS), malondialdehyde, non-protein thiol levels, antioxidant capacity and enzymatic antioxidant activities were investigated in plasma, aorta and/or mesenteric arteries. After one hour of AlCl 3 exposure serum Al levels attained 147.7 ± 25.0 μg/L. Al treatment: 1) did not affect blood pressure, heart rate and vasodilator responses induced by acetylcholine or sodium nitroprusside; 2) decreased phenylephrine-induced vasoconstrictor responses; 3) increased endothelial modulation of contractile responses, NO release and vascular ROS production from NADPH oxidase; 4) increased plasmatic, aortic and mesenteric malondialdehyde and ROS production, and 5) decreased antioxidant capacity and affected the antioxidant biomarkers non-protein thiol levels, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymatic activities. Conclusion: AlCl 3 -acute exposure reduces vascular reactivity. This effect is associated with increased NO production, probably acting on K + channels, which seems to occur as a compensatory mechanism against Al-induced oxidative stress. Our results suggest that Al exerts toxic effects to the vascular system. - Highlights:

  3. Cardiovascular responses of peripheral artery disease patients during resistance exercise

    Directory of Open Access Journals (Sweden)

    Ana Patrícia Ferreira Gomes

    2015-03-01

    Full Text Available BACKGROUND: Resistance training has been used for the treatment of patients with peripheral artery disease (PAD. However, cardiovascular responses during this type of exercise have not been fully elucidated in these patients. OBJECTIVES: To analyze the cardiovascular responses during resistance exercise and to verify whether there are any correlations between these responses and disease severity or blood pressure levels in patients with PAD. METHODS: Seventeen PAD patients performed one set of 10 repetitions of knee extension exercise with an intensity of 50% of one repetition maximum. The responses of systolic blood pressure (SBP, diastolic blood pressure (DBP and heart rate (HR were continuously monitored using the finger photoplethysmography technique. The rate-pressure product (RPP was obtained by multiplication of SBP and HR. RESULTS: During the resistance exercises there were significant increases in SBP (126 ± 14 vs. 184 ± 20 mmHg, p<0.001, DBP (68 ± 8 vs. 104 ± 14 mmHg, p<0.001, HR (76 ± 18 vs. 104 ± 30 bpm, p<0.001 and RPP (9523 ± 2115 vs. 19103 ± 6098 mmHg x bpm, p<0.001. A negative correlation was observed between relative change (Δ in SBP and SBP at rest (r =-0.549, p=0.022. On the other hand, there was no relationship between Δ SBP and the ankle-brachial index (r=0.076, p=0.771. CONCLUSION: Increases in cardiovascular variables were observed during resistance exercise in PAD patients. The highest increases occurred in patients with lower SBP levels at resting.

  4. Sympathetic reflex control of resistance in collateral arteries in the lower extremities in patients with diabetes mellitus

    DEFF Research Database (Denmark)

    Agerskov, K; Tønnesen, K H

    1982-01-01

    in the brachial artery, femoral artery and vein and popliteal artery and vein. Relative blood flow was calculated as the relative change in arterio-venous oxygen saturation. Absolute blood flow in the common femoral artery was measured by an indicator dilution technique. Resistance of the collateral arteries...

  5. [RESISTANT ARTERIAL HYPERTENSION – APPROACH TO PATIENT IN FAMILY MEDICINE].

    Science.gov (United States)

    Diminić-Lisica, I; Bukmir, L; Lisica, I

    2016-12-01

    Increasing the proportion of patients with controlled hypertension implies understanding and systematic approach to patients with resistant hypertension. In the past decades, an increase in the prevalence of resistant arterial hypertension (RAH) has been observed and the incidence of this problem is becoming greater in the practice of family physicians. Patients with RAH have a higher prevalence of target organ damage as compared with patients having achieved target blood pressure values, and their risk of an adverse cardiovascular event is tripled. RAH is defined as hypertension in which there is no satisfactory control of blood pressure despite compliance to lifestyle changes and taking at least three drugs in full doses, one of which has to be a diuretic. The most important risk factors for resistance to treatment are older age, obesity, smoking, excessive intake of salt and alcohol, the presence of left ventricular hypertrophy, chronic renal failure, diabetes, inadequate baroreflex pathway, chronic stress and associated mental states, use of some drugs, and all forms of secondary hypertension. One-fifth of patients with RAH have primary aldosteronism. Obstructive sleep apnea is a common cause of RAH, and literature reports point to its increasing frequency. Optimal treatment involves a combination of three drugs, one of which is a diuretic. Use of mineralocorticoid antagonist as the fourth drug has shown significant efficacy even in patients who do not have elevated levels of aldosterone. New invasive methods of treatment include renal denervation and permanent electrical stimulation of the carotid sinus. The aim of this paper is to emphasize the importance of RAH as a cardiovascular risk factor, along with early detection and treatment at the family medicine level and timely referral to additional procedures to treat the specific forms of RAH.

  6. Structural remodeling of coronary resistance arteries: effects of age and exercise training.

    Science.gov (United States)

    Hanna, Mina A; Taylor, Curtis R; Chen, Bei; La, Hae-Sun; Maraj, Joshua J; Kilar, Cody R; Behnke, Bradley J; Delp, Michael D; Muller-Delp, Judy M

    2014-09-15

    Age is known to induce remodeling and stiffening of large-conduit arteries; however, little is known of the effects of age on remodeling and mechanical properties of coronary resistance arteries. We employed a rat model of aging to investigate whether 1) age increases wall thickness and stiffness of coronary resistance arteries, and 2) exercise training reverses putative age-induced increases in wall thickness and stiffness of coronary resistance arteries. Young (4 mo) and old (21 mo) Fischer 344 rats remained sedentary or underwent 10 wk of treadmill exercise training. Coronary resistance arteries were isolated for determination of wall-to-lumen ratio, effective elastic modulus, and active and passive responses to changes in intraluminal pressure. Elastin and collagen content of the vascular wall were assessed histologically. Wall-to-lumen ratio increased with age, but this increase was reversed by exercise training. In contrast, age reduced stiffness, and exercise training increased stiffness in coronary resistance arteries from old rats. Myogenic responsiveness was reduced with age and restored by exercise training. Collagen-to-elastin ratio (C/E) of the wall did not change with age and was reduced with exercise training in arteries from old rats. Thus age induces hypertrophic remodeling of the vessel wall and reduces the stiffness and myogenic function of coronary resistance arteries. Exercise training reduces wall-to-lumen ratio, increases wall stiffness, and restores myogenic function in aged coronary resistance arteries. The restorative effect of exercise training on myogenic function of coronary resistance arteries may be due to both changes in vascular smooth muscle phenotype and expression of extracellular matrix proteins. Copyright © 2014 the American Physiological Society.

  7. Estimation of the flow resistances exerted in coronary arteries using a vessel length-based method.

    Science.gov (United States)

    Lee, Kyung Eun; Kwon, Soon-Sung; Ji, Yoon Cheol; Shin, Eun-Seok; Choi, Jin-Ho; Kim, Sung Joon; Shim, Eun Bo

    2016-08-01

    Flow resistances exerted in the coronary arteries are the key parameters for the image-based computer simulation of coronary hemodynamics. The resistances depend on the anatomical characteristics of the coronary system. A simple and reliable estimation of the resistances is a compulsory procedure to compute the fractional flow reserve (FFR) of stenosed coronary arteries, an important clinical index of coronary artery disease. The cardiac muscle volume reconstructed from computed tomography (CT) images has been used to assess the resistance of the feeding coronary artery (muscle volume-based method). In this study, we estimate the flow resistances exerted in coronary arteries by using a novel method. Based on a physiological observation that longer coronary arteries have more daughter branches feeding a larger mass of cardiac muscle, the method measures the vessel lengths from coronary angiogram or CT images (vessel length-based method) and predicts the coronary flow resistances. The underlying equations are derived from the physiological relation among flow rate, resistance, and vessel length. To validate the present estimation method, we calculate the coronary flow division over coronary major arteries for 50 patients using the vessel length-based method as well as the muscle volume-based one. These results are compared with the direct measurements in a clinical study. Further proving the usefulness of the present method, we compute the coronary FFR from the images of optical coherence tomography.

  8. Association of insulin resistance and coronary artery remodeling: an intravascular ultrasound study

    OpenAIRE

    Kim, Sang-Hoon; Moon, Jae-Youn; Lim, Yeong Min; Kim, Kyung Ho; Yang, Woo-In; Sung, Jung-Hoon; Yoo, Seung Min; Kim, In Jai; Lim, Sang-Wook; Cha, Dong-Hun; Cho, Seung-Yun

    2015-01-01

    Background There are few studies that investigated the correlation between insulin resistance (IR) and the coronary artery remodeling. The aim of the study is to investigate the association of IR measured by homeostasis model assessment of insulin resistance (HOMA-IR) and coronary artery remodeling evaluated by intravascular ultrasound (IVUS). Methods A total of 298 consecutive patients who received percutaneous coronary interventions under IVUS guidance were retrospectively enrolled. The val...

  9. Fractalkine depresses cardiomyocyte contractility.

    Directory of Open Access Journals (Sweden)

    David Taube

    Full Text Available Our laboratory reported that male mice with cardiomyocyte-selective knockout of the prostaglandin E2 EP4 receptor sub-type (EP4 KO exhibit reduced cardiac function. Gene array on left ventricles (LV showed increased fractalkine, a chemokine implicated in heart failure. We therefore hypothesized that fractalkine is regulated by PGE2 and contributes to depressed contractility via alterations in intracellular calcium.Fractalkine was measured in LV of 28-32 week old male EP4 KO and wild type controls (WT by ELISA and the effect of PGE2 on fractalkine secretion was measured in cultured neonatal cardiomyocytes and fibroblasts. The effect of fractalkine on contractility and intracellular calcium was determined in Fura-2 AM-loaded, electrical field-paced cardiomyocytes. Cardiomyocytes (AVM from male C57Bl/6 mice were treated with fractalkine and responses measured under basal conditions and after isoproterenol (Iso stimulation.LV fractalkine was increased in EP4 KO mice but surprisingly, PGE2 regulated fractalkine secretion only in fibroblasts. Fractalkine treatment of AVM decreased both the speed of contraction and relaxation under basal conditions and after Iso stimulation. Despite reducing contractility after Iso stimulation, fractalkine increased the Ca(2+ transient amplitude but decreased phosphorylation of cardiac troponin I, suggesting direct effects on the contractile machinery.Fractalkine depresses myocyte contractility by mechanisms downstream of intracellular calcium.

  10. Remodelling of the microarchitecture of resistance arteries in cardiovascular diseases

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Brewer, Jonathan R.; Leurgans, Thomas

    is largely unknown, and the presented project aims to investigate this. Innovative multiphoton excitation microscopy will be applied on live (vital), isolated, cannulated and pressurized arteries from parietal pericardial biopsies obtained during open cardiac surgery (coronary artery bypass grafting...... and cardiac valve replacement surgery). Using the intrinsic properties of the live tissue, that is the autofluorescence of elastin and smooth muscle/endothelial cells and the second harmonic generation from collagen fibers, the quantity, distribution and orientation of elastin structures, collagen fibers...

  11. Effects of pinacidil on contractile proteins in high K(+)-treated intact, and in beta-escin-treated skinned smooth muscle of the rabbit mesenteric artery.

    Science.gov (United States)

    Itoh, T.; Suzuki, S.; Kuriyama, H.

    1991-01-01

    1. The effects of pinacidil were investigated on changes in cellular Ca2+ concentration ([Ca2+]i) and tension in intact and chemically skinned smooth muscle strips of the rabbit mesenteric artery. 2. High K+ (128 mM) produced a large phasic followed by a tonic increase in [Ca2+]i and tension in intact muscle strips. Pinacidil at 10 microM but not 1 microM, inhibited the phasic and tonic contractions induced by 128 mM K+ without a corresponding change in [Ca2+]i. 3. In beta-escin-treated skinned smooth muscle, the minimum Ca2+ concentration that produced contraction was 0.1 microM and the maximum contraction was obtained at 10 microM. Pinacidil at 10 microM but not 1 microM, shifted the pCa-tension relation curve to the right and also inhibited the maximum contraction induced by Ca2+. The concentrations of Ca2+ required for half maximal tension were 0.9 microM in control and 1.5 microM in the presence of 10 microM pinacidil. Calmodulin (2 microM) increased the contraction induced by 0.3 microM Ca2+ (but not by 10 microM Ca2+) in the skinned strips. Pinacidil (10 microM) inhibited the contraction induced by 0.3 microM or 10 microM Ca2+ in the presence of 2 microM calmodulin. 4. Noradrenaline (NA, 10 microM) with guanosine triphosphate (GTP, 3 microM), guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S, 3 microM) or 12-O-tetradecanoylphorbol-13-acetate (TPA, 0.1 microM) all enhanced the contraction induced by 0.3 microM Ca2+. Pinacidil (10 microM) inhibited the contraction induced by 0.3 microM Ca2+ more strongly in the presence of the above agents than in their absence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1933133

  12. Arterial stiffness and peripheral vascular resistance in offspring of hypertensive parents

    DEFF Research Database (Denmark)

    Buus, Niels Henrik; Carlsen, Rasmus K; Khatir, Dinah S

    2018-01-01

    AIM: Established essential hypertension is associated with increased arterial stiffness and peripheral resistance, but the extent of vascular changes in persons genetically predisposed for essential hypertension is uncertain. METHODS: Participants from the Danish Hypertension Prevention Project...... resting and minimal resistance [forearm resting vascular resistance (Rrest) and forearm minimal vascular resistance (Rmin)]. RESULTS: DHyPP patients with participating spouses had higher 24-h mean BP (94 ± 1 vs. 88 ± 1 mmHg, P ... and peripheral resistance are still normal....

  13. Translational value of mechanical and vasomotor properties of mouse isolated mesenteric resistance-sized arteries

    DEFF Research Database (Denmark)

    Outzen, Emilie Middelbo; Zaki, Marina; Abdolalizadeh, Bahareh

    2015-01-01

    Mice are increasingly used in vascular research for studying perturbations and responses to vasoactive agents in small artery preparations. Historically, small artery function has preferably been studied in rat isolated mesenteric resistance-sized arteries (MRA) using the wire myograph technique...... for maximal active force development in mouse MRA were not significantly different to those determined in rat MRA. Furthermore, we found that the observed concentration-dependent vasomotor responses of mouse MRA to noradrenaline, phenylephrine, angiotensin II, sarafotoxin 6c, 5-hydroxytryptamine, carbachol...

  14. Renal artery anatomy affects the blood pressure response to renal denervation in patients with resistant hypertension.

    Science.gov (United States)

    Hering, Dagmara; Marusic, Petra; Walton, Antony S; Duval, Jacqueline; Lee, Rebecca; Sata, Yusuke; Krum, Henry; Lambert, Elisabeth; Peter, Karlheinz; Head, Geoff; Lambert, Gavin; Esler, Murray D; Schlaich, Markus P

    2016-01-01

    Renal denervation (RDN) has been shown to reduce blood pressure (BP), muscle sympathetic nerve activity (MSNA) and target organ damage in patients with resistant hypertension (RH) and bilateral single renal arteries. The safety and efficacy of RDN in patients with multiple renal arteries remains unclear. We measured office and 24-hour BP at baseline, 3 and 6 months following RDN in 91 patients with RH, including 65 patients with single renal arteries bilaterally (group 1), 16 patients with dual renal arteries on either one or both sides (group 2) and 10 patients with other anatomical constellations or structural abnormalities (group 3). Thirty nine out of 91 patients completed MSNA at baseline and follow-up. RDN significantly reduced office and daytime SBP in group 1 at both 3 and 6 months follow-up (Prenal anatomy, the presence of single renal arteries with or without structural abnormalities is associated with a more pronounced BP and MSNA lowering effect than the presence of dual renal arteries in patients with RH. However, when patients with dual renal arteries received renal nerve ablation in all arteries there was trend towards a greater BP reduction. Insufficient renal sympathetic nerve ablation may account for these differences. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Elastin and Mechanics of Pig Pericardial Resistance Arteries (pPRA)

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Leurgans, Thomas; Rosenstand, Kristoffer

    Resistance arteries are remodeled in hypertension and diabetes. Elastin was reported to play a role herein. The parietal pericardium is opened during cardio-thoracic surgeries and might be a valuable biopsy for research in cardio-vascular diseases. We tested the hypothesis that resistance arteries...... fibrils between their medial smooth muscle cells and a net-stocking-like internal elastic lamina underneath the endothelium (perforated sheet with fenestrae in rMRA and rBA). Isolated pPRA lengthen ~30% when pressurized to 100mmHg, like rMRA but not rBA (

  16. Responses of iliac conduit artery and hindlimb resistance vessels to luminal hyperfructosemia in the anaesthetized pig.

    Science.gov (United States)

    Ruane-O'Hora, T; Edge, D; Shortt, C M; Markos, F; Noble, M I M

    2013-12-01

    High fructose levels are found in diabetes mellitus, associated with high corn syrup diets, and have been claimed to cause hypertension. As the direct effects on conduit and resistance arteries have not been previously reported, we measured these in vivo in the anaesthetized pig with instrumented iliac arteries. Experiments were performed on the iliac artery preparation in the anaesthetized pig: blood flow, diameter and pressure were measured in the iliac. The change in diameter of an occluded iliac artery segment filled with hyperfructosemic (15 μm) blood was 89.5 ± 22.1 μm (mean ± SE), contrasted with 7.7 ± 13.06 μm control (P = 0.005, paired t-test, n = 6). There was no significant difference when compared with blood containing both hyperfructosemic blood and the nitric oxide synthesis inhibitor, N(G)-nitro-l-arginine methyl ester (250 μg mL(-1)). Step changes in pressure and flow were achieved by progressive arterial stenosis during control saline and 15 μm min(-1) fructose downstream intra-arterial infusions. Linear regression of the step changes in blood pressure versus the instantaneous step changes in blood flow showed a statistically significant decrease in slope of the conductance (P resistance. Peripheral autoregulation and conduit artery shear-stress-mediated dilatation were not significantly altered. An elevated level of fructose caused dilatation of a conduit artery but constriction of resistance vessels. The latter effect could account, if maintained long-term, for the hypertension claimed to be due to hyperfuctosemia. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  17. Acute Effect on Arterial Stiffness after Performing Resistance Exercise by Using the Valsalva Manoeuvre during Exertion

    Directory of Open Access Journals (Sweden)

    Wai Yip Vincent Mak

    2015-01-01

    Full Text Available Background. Performing resistance exercise could lead to an increase in arterial stiffness. Objective. We investigate the acute effect on arterial stiffness by performing Valsalva manoeuvre during resistance exercise. Materials and Methods. Eighteen healthy young men were assigned to perform bicep curls by using two breathing techniques (exhalation and Valsalva manoeuvre during muscle contraction on two separate study days. Carotid pulsed wave velocity (cPWV was measured as an indicator to reflect the body central arterial stiffness using a high-resolution ultrasound system, and its value was monitored repeatedly at three predefined time intervals: before resistance exercise, immediately after exercise, and 15 minutes after exercise. Results. At the 0th minute after resistance exercise was performed using the Valsalva manoeuvre during exertion, a significant increase in cPWV (4.91 m/s ± 0.52 compared with the baseline value (4.67 m/s ± 0.32, P=0.008 was observed, and then it nearly returned to its baseline value at the 15th minute after exercise (4.66 m/s ± 0.44, P=0.010. These findings persisted after adjusting for age, body mass index, and systolic blood pressure. Conclusion. Our result suggests short duration of resistance exercise may provoke a transient increase in central arterial stiffness in healthy young men.

  18. Sympathetic reflex control of resistance in collateral arteries in the lower extremities in patients with diabetes mellitus

    DEFF Research Database (Denmark)

    Agerskov, K; Tønnesen, K H

    1982-01-01

    The vascular response in the lower extremities to 40 degrees head-up tilt was studied in 5 patients with occlusion of the superficial femoral artery and maturity onset diabetes mellitus with symptoms suggesting autonomic neuropathy. The pressure measurements were performed via catheters placed...... in the brachial artery, femoral artery and vein and popliteal artery and vein. Relative blood flow was calculated as the relative change in arterio-venous oxygen saturation. Absolute blood flow in the common femoral artery was measured by an indicator dilution technique. Resistance of the collateral arteries...

  19. Renal Artery Stenosis in Patients with Resistant Hypertension: Stent It or Not?

    Science.gov (United States)

    Van der Niepen, Patricia; Rossignol, Patrick; Lengelé, Jean-Philippe; Berra, Elena; Sarafidis, Pantelis; Persu, Alexandre

    2017-01-01

    After three large neutral trials in which renal artery revascularization failed to reduce cardiovascular and renal morbidity and mortality, renal artery stenting became a therapeutic taboo. However, this is probably unjustified as these trials have important limitations and excluded patients most likely to benefit from revascularization. In particular, patients with severe hypertension were often excluded and resistant hypertension was either poorly described or not conform to the current definition. Effective pharmacological combination treatment can control blood pressure in most patients with renovascular hypertension. However, it may also induce further renal hypoperfusion and thus accelerate progressive loss of renal tissue. Furthermore, case reports of patients with resistant hypertension showing substantial blood pressure improvement after successful revascularization are published over again. To identify those patients who would definitely respond to renal artery stenting, properly designed randomized clinical trials are definitely needed.

  20. Activation of resistance arteries with endothelin-1: From vasoconstriction to functional adaptation and remodeling

    NARCIS (Netherlands)

    Bakker, Erik N. T. P.; Buus, Carsten L.; VanBavel, Ed; Mulvany, Michael J.

    2004-01-01

    Remodeling of resistance arteries is a key feature in hypertension. We studied the transition of vasoconstriction to remodeling in isolated rat skeletal muscle arterioles. Arterioles activated with 10 nM endothelin-1 showed functional adaptation when kept at low distension in a wire myograph setup,

  1. Effects of streptozotocin-induced diabetes on the pharmacology of rat conduit and resistance intrapulmonary arteries

    Directory of Open Access Journals (Sweden)

    Howarth Frank C

    2009-01-01

    Full Text Available Abstract Background Poor control of blood glucose in diabetes is known to promote vascular dysfunction and hypertension. Diabetes was recently shown to be linked to an increased prevalence of pulmonary hypertension. The aim of this study was to determine how the pharmacological reactivity of intrapulmonary arteries is altered in a rat model of diabetes. Methods Diabetes was induced in rats by the β-cell toxin, streptozotocin (STZ, 60 mg/kg, and isolated conduit and resistance intrapulmonary arteries studied 3–4 months later. Isometric tension responses to the vasoconstrictors phenylephrine, serotonin and PGF2α, and the vasodilators carbachol and glyceryl trinitrate, were compared in STZ-treated rats and age-matched controls. Results STZ-induced diabetes significantly blunted the maximum response of conduit, but not resistance pulmonary arteries to phenylephrine and serotonin, without a change in pEC50. Agonist responses were differentially reduced, with serotonin (46% smaller affected more than phenylephrine (32% smaller and responses to PGF2α unaltered. Vasoconstriction caused by K+-induced depolarisation remained normal in diabetic rats. Endothelium-dependent dilation to carbachol and endothelium-independent dilation to glyceryl trinitrate were also unaffected. Conclusion The small resistance pulmonary arteries are relatively resistant to STZ-induced diabetes. The impaired constrictor responsiveness of conduit vessels was agonist dependent, suggesting possible loss of receptor expression or function. The observed effects cannot account for pulmonary hypertension in diabetes, rather the impaired reactivity to vasoconstrictors would counteract the development of pulmonary hypertensive disease.

  2. Local over-expression of VEGF-DΔNΔC in the uterine arteries of pregnant sheep results in long-term changes in uterine artery contractility and angiogenesis.

    Science.gov (United States)

    Mehta, Vedanta; Abi-Nader, Khalil N; Shangaris, Panicos; Shaw, S W Steven; Filippi, Elisa; Benjamin, Elizabeth; Boyd, Michael; Peebles, Donald M; Martin, John; Zachary, Ian; David, Anna L

    2014-01-01

    The normal development of the uteroplacental circulation in pregnancy depends on angiogenic and vasodilatory factors such as vascular endothelial growth factor (VEGF). Reduced uterine artery blood flow (UABF) is a common cause of fetal growth restriction; abnormalities in angiogenic factors are implicated. Previously we showed that adenovirus (Ad)-mediated VEGF-A165 expression in the pregnant sheep uterine artery (UtA) increased nitric oxide synthase (NOS) expression, altered vascular reactivity and increased UABF. VEGF-D is a VEGF family member that promotes angiogenesis and vasodilatation but, in contrast to VEGF-A, does not increase vascular permeability. Here we examined the effect of Ad.VEGF-DΔNΔC vector encoding a fully processed form of VEGF-D, on the uteroplacental circulation. UtA transit-time flow probes and carotid artery catheters were implanted in mid-gestation pregnant sheep (n = 5) to measure baseline UABF and maternal haemodynamics respectively. 7-14 days later, after injection of Ad.VEGF-DΔNΔC vector (5×10(11) particles) into one UtA and an Ad vector encoding β-galactosidase (Ad.LacZ) contralaterally, UABF was measured daily until scheduled post-mortem examination at term. UtAs were assessed for vascular reactivity, NOS expression and endothelial cell proliferation; NOS expression was studied in ex vivo transduced UtA endothelial cells (UAECs). At 4 weeks post-injection, Ad.VEGF-DΔNΔC treated UtAs showed significantly lesser vasoconstriction (Emax144.0 v/s 184.2, p = 0.002). There was a tendency to higher UABF in Ad.VEGF-DΔNΔC compared to Ad.LacZ transduced UtAs (50.58% v/s 26.94%, p = 0.152). There was no significant effect on maternal haemodynamics. An increased number of proliferating endothelial cells and adventitial blood vessels were observed in immunohistochemistry. Ad.VEGF-DΔNΔC expression in cultured UAECs upregulated eNOS and iNOS expression. Local over-expression of VEGF-DΔNΔC in the UtAs of pregnant mid

  3. Pleural opening impairs respiratory system compliance and resistance in off-pump coronary artery bypass grafting.

    Science.gov (United States)

    Tavolaro, K C; Guizilini, S; Bolzan, D W; Dauar, R B; Buffolo, E; Succi, J E; Gomes, W J

    2010-12-01

    This study evaluated the effect of pleurotomy on respiratory system compliance and resistance in off-pump coronary artery bypass (OPCAB) using the left internal thoracic artery (LITA). Thirty-two patients were prospectively allocated into two groups: OP group (n = 16 patients with open left pleural cavity); IP group (N.=16 patients with intact pleural cavity). Static and dynamic lung compliance and total respiratory system resistance calculation were recorded at anesthesia induction (before chest opening) and immediately after chest closure. Static lung compliance values significantly decreased after chest closure in both groups (P tube insertion induced significant reduction in static lung compliance and increase in total respiratory system resistance, furthermore contributing to impair pulmonary dysfunction in the early postoperative period after OPCAB.

  4. Elastomeric contractile actuators for hand rehabilitation splints

    Science.gov (United States)

    Carpi, Federico; Mannini, Andrea; De Rossi, Danilo

    2008-03-01

    The significant electromechanical performances typically shown by dielectric elastomer actuators make this polymer technology particularly attractive for possible active orthoses for rehabilitation. Folded contractile actuators made of dielectric elastomers were recently described as a simple configuration, suitable to easily implement linear contractile devices. This paper describes an application of folded actuators for so-called hand splints: they consist of orthotic systems for hand rehabilitation. The dynamic versions of the state-of-the-art splints typically include elastic bands, which exert a passive elastic resistance to voluntary elongations of one or more fingers. In order to provide such splints with the possibility of electrically modulating the compliance of the resistive elements, the substitution of the passive elastic bands with the contractile actuators is here described. The electrical activation of the actuators is used to vary the compliance of the system; this enables modulations of the force that acts as an antagonist to voluntary finger movements, according to programmable rehabilitation exercises. The paper reports results obtained from the first prototype implementations of such a type of system.

  5. Assessing Collagen and Elastin Pressure-Dependent Microarchitectures in Live, Human Resistance Arteries by Label-Free Fluorescence Microscopy

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Thorsted, Bjarne; Brewer, Jonathan R.

    2017-01-01

    The pathogenic contribution of resistance artery remodeling is documented in essential hypertension, diabetes and the metabolic syndrome. Investigations and development of microstructurally motivated mathematical models for understanding the mechanical properties of human resistance arteries...... in health and disease have the potential to aid understanding how disease and medical treatments affect the human microcirculation. To develop these mathematical models, it is essential to decipher the relationship between the mechanical and microarchitectural properties of the microvascular wall....... In this work, we describe an ex vivo method for passive mechanical testing and simultaneous label-free three-dimensional imaging of the microarchitecture of elastin and collagen in the arterial wall of isolated human resistance arteries. The imaging protocol can be applied to resistance arteries of any species...

  6. Assessing Collagen and Elastin Pressure-Dependent Microarchitectures in Live, Human Resistance Arteries by Label-Free Fluorescence Microscopy

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Thorsted, Bjarne; Brewer, Jonathan R.

    2017-01-01

    are performed on live, perfused arteries, however, an alternative approach using standard video-microscopy pressure myography in combination with post-fixation imaging of re-pressurized vessels is discussed. This alternative method provides users with different options for analysis approaches. The inclusion....... In this work, we describe an ex vivo method for passive mechanical testing and simultaneous label-free three-dimensional imaging of the microarchitecture of elastin and collagen in the arterial wall of isolated human resistance arteries. The imaging protocol can be applied to resistance arteries of any species...

  7. Therapeutic resistance exercises for individuals with peripheral arterial obstructive disease: evidence for prescription

    OpenAIRE

    Câmara, Lucas Caseri; Santarém, José Maria; Wolosker, Nelson; Dias, Raphael Mendes Ritti

    2007-01-01

    A prática regular de exercícios é parte do tratamento clínico inicial para pacientes com doença arterial obstrutiva periférica. Nesse sentido, a utilização de exercícios contra resistência (exercícios resistidos) tem sido amplamente recomendada para diferentes populações, especialmente para pessoas idosas com e sem doenças associadas. Os poucos trabalhos encontrados utilizando essa forma de exercícios em pacientes com doença arterial obstrutiva periférica documentam a sua eficiência terapêuti...

  8. Systolic Intrinsic Frequency and Various Measures of Left Ventricle Contractility

    Science.gov (United States)

    Pahlevan, Niema

    2017-11-01

    There has been growing interest during past six decades to introduce new indices for quantifying left ventricular (LV) contractility. We have recently introduced a new method, called intrinsic frequency (IF), for analyzing the dynamics of systemic circulation. IF method models LV and arterial network as an object rotating around an origin where the angular velocity of the rotation during systole (when LV and arterial network are coupled) and diastole (when arterial network is decoupled) are intrinsic frequencies, ω1 and ω2 respectively. ω1 and ω2 can be extracted from a carotid pulse waveform using IF method. In this study, Huntington Medical Research Institutes heart study data have been used to compare ω1 with various measures of LV contractility such as ejection fraction, mean velocity of circumferential fiber shortening, LV end-systolic meridional wall stress, and maximal LV power corrected for end-diastolic volume. Here, LV contractility indices were computed noninvasively from cardiac MRI and tonometry data. The results indicate that ω1 can be used as a surrogate of LV contractility. This is clinically significant since ω1 can be accurately obtained by a standard iPhone camera.

  9. Insulin resistance and associated dysfunction of resistance vessels and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2005-01-01

    This review looks at the alterations in the systemic haemodynamics of patients with chronic liver disease (cirrhosis) in relation to essential hypertension and arterial hypertension of renal origin. Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic...

  10. Value of Resistive lndex of the lntrascrotal Artery in ScrotaI Inflammatory Disease

    International Nuclear Information System (INIS)

    Jee, Won Hee; Yoon, Yeo Dong; Hwang, Sung Su; Choi, Byung Gil; Son, Kyung Myung; Lee, Sung Yong; Kim, Ki Tae; Shinn, Kyung Sub

    1995-01-01

    This prospective study was designed to investigate the utility of resistive indices(RIs) of intratesticular and epididymal arteries in inflammatory scrotal disease. Gray-scale and color Doppler ultrasonographic images were obtained in 19 consecutive patients of scrotal inflammatory disease from Nov.1993 to Oct. 1994. Eleven cases of epididymitis and 11 of epididymoorchitis(EO) were included. RIs of epididymal and centripetal arteries were calculated in 19 patients and 30 cases of control. All EO and epididymitis cases showed increased color signal at color Doppler ultrasonogram at representative sites. Mean RI of centripetal artery was 0.46±0.06 in EO and 0.66±0.07 in normal control, hence RI in EO was significantly lower than that of normal control(P<0.001). The diagnostic sensitivity was 91% when the value of 0.5 or less is estimated abnormal.Mean RI of centripetal artery was 0.67±0.07 in epididymitis, and was not significantly different from that of normal control(P=0.687). Mean RI of epididymal artery in epididymitis and EO was 0.48±0.12 and resistive index of all patients were below 0.7. Color Doppler can demonstrate the hyperemic response to scrotal inflammatory disease that it can supplement the gray scale finding leading to increased diagnostic confidence. RI of centripetal artery may be confirmative in the diagnosis of inflammatory scrotal inflammatory scrotal diseases when increased color flow on color flow imaging is present

  11. Mechanisms of endothelial dysfunction in resistance arteries from patients with end-stage renal disease.

    Directory of Open Access Journals (Sweden)

    Leanid Luksha

    Full Text Available The study focuses on the mechanisms of endothelial dysfunction in the uremic milieu. Subcutaneous resistance arteries from 35 end-stage renal disease (ESRD patients and 28 matched controls were studied ex-vivo. Basal and receptor-dependent effects of endothelium-derived factors, expression of endothelial NO synthase (eNOS, prerequisites for myoendothelial gap junctions (MEGJ, and associations between endothelium-dependent responses and plasma levels of endothelial dysfunction markers were assessed. The contribution of endothelium-derived hyperpolarizing factor (EDHF to endothelium-dependent relaxation was impaired in uremic arteries after stimulation with bradykinin, but not acetylcholine, reflecting the agonist-specific differences. Diminished vasodilator influences of the endothelium on basal tone and enhanced plasma levels of asymmetrical dimethyl L-arginine (ADMA suggest impairment in NO-mediated regulation of uremic arteries. eNOS expression and contribution of MEGJs to EDHF type responses were unaltered. Plasma levels of ADMA were negatively associated with endothelium-dependent responses in uremic arteries. Preserved responses of smooth muscle to pinacidil and NO-donor indicate alterations within the endothelium and tolerance of vasodilator mechanisms to the uremic retention products at the level of smooth muscle. We conclude that both EDHF and NO pathways that control resistance artery tone are impaired in the uremic milieu. For the first time, we validate the alterations in EDHF type responses linked to kinin receptors in ESRD patients. The association between plasma ADMA concentrations and endothelial function in uremic resistance vasculature may have diagnostic and future therapeutic implications.

  12. Imaging and modeling of acute pressure-induced changes of collagen and elastin microarchitectures in pig and human resistance arteries

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Leurgans, Thomas M; Spronck, Bart

    2017-01-01

    The impact of disease related changes in the extracellular matrix (ECM) on the mechanical properties of human resistance arteries largely remains to be established. Resistance arteries from both pig and human parietal pericardium (PRA) display a different ECM microarchitecture compared...... changes of elastin and collagen upon pressurization. In conclusion, we show for the first time in resistance arteries a quantitative relationship between pressure-induced changes in the extracellular matrix and the arterial wall mechanics. The strength of the integrated methods invites for future detailed...... to frequently used rodent mesenteric arteries. We hypothesized that the biaxial mechanics of PRA mirror pressure induced changes in the ECM microarchitecture. This was tested using isolated pig PRA as model system, integrating vital imaging, pressure myography and mathematical modeling. Collagenase and elastase...

  13. Role of cytochrome P-450 4A in oxygen sensing and NO production in rat cremaster resistance arteries

    NARCIS (Netherlands)

    Kerkhof, C. J.; Bakker, E. N.; Sipkema, P.

    1999-01-01

    The role of arachidonic acid metabolism and nitric oxide (NO) in hypoxia-induced changes of vascular tone was investigated in first-order cannulated rat cremaster muscle resistance arteries. Spontaneous tone reduced arterial diameter from 179 +/- 2 micrometer (fully dilated) to 98 +/- 3 micrometer

  14. Obese children and adolescents have elevated nighttime blood pressure independent of insulin resistance and arterial stiffness

    DEFF Research Database (Denmark)

    Hvidt, Kristian N; Olsen, Michael H; Holm, Jens-Christian

    2014-01-01

    in obese children and adolescents. METHODS: Ninety-two obese patients aged 10-18 years were compared with 49 healthy control individuals. Insulin resistance was measured as the homeostatic assessment model (HOMA), and arterial stiffness was measured as carotid-femoral pulse wave velocity (cfPWV). RESULTS...... group. HOMA index (obese: median = 3.7, interquartile range (IQR) = 2.3-6.0; control: median = 2.6, IQR = 1.8-3.4; P = 0.002) was higher, whereas cfPWV (obese: 4.8±0.8 m/s; control: 5.1±0.6 m/s; P = 0.03) was lower in the obese group. CfPWV was not related to logHOMA index. In multiple regression...... analyses, the higher nighttime BP in the obese group was independent of logHOMA and cfPWV. CONCLUSIONS: Obese children had a higher nighttime BP when compared with the control group independently of insulin resistance and arterial stiffness. No relationship was found between insulin resistance and arterial...

  15. Accessory renal arteries: Prevalence in resistant hypertension and an important role in nonresponse to radiofrequency renal denervation

    Energy Technology Data Exchange (ETDEWEB)

    VonAchen, Paige [Minneapolis Heart Institute and Foundation at Abbott Northwestern Hospital, Minneapolis, MN (United States); Hamann, Jason [Boston Scientific Corporation, Maple Grove, MN (United States); Houghland, Thomas; Lesser, John R.; Wang, Yale; Caye, David; Rosenthal, Kristi; Garberich, Ross F. [Minneapolis Heart Institute and Foundation at Abbott Northwestern Hospital, Minneapolis, MN (United States); Daniels, Mary [Vital Images/Toshiba, Minnetonka, MN (United States); Schwartz, Robert S., E-mail: rss@rsschwartz.com [Minneapolis Heart Institute and Foundation at Abbott Northwestern Hospital, Minneapolis, MN (United States)

    2016-10-15

    Objective: The aim of this study was to understand the role of accessory renal arteries in resistant hypertension, and to establish their role in nonresponse to radiofrequency renal denervation (RDN) procedures. Background: Prior studies suggest a role for accessory renal arteries in hypertensive syndromes, and recent clinical trials of renal denervation report that these anomalies are highly prevalent in resistant hypertension. This study evaluated the relationships among resistant hypertension, accessory renal arteries, and the response to radiofrequency (RF) renal denervation. Methods: Computed Tomography Angiography (CTA) and magnetic resonance imaging (MRI) scans from 58 patients with resistant hypertension undergoing RF renal denervation (RDN) were evaluated. Results were compared with CT scans in 57 healthy, normotensive subjects undergoing screening as possible renal transplant donors. All scans were carefully studied for accessory renal arteries, and were correlated with long term blood pressure reduction. Results: Accessory renal arteries were markedly more prevalent in the hypertensive patients than normotensive renal donors (59% vs 32% respectively, p = 0.004). RDN had an overall nonresponse rate of 29% (response rate 71%). Patients without accessory vessels had a borderline higher response rate to RDN than those with at least one accessory vessel (83% vs 62% respectively, p = 0.076) and a higher RDN response than patients with untreated accessory arteries (83% vs 55%; p = 0.040). For accessory renal arteries and nonresponse, the sensitivity was 76%, specificity 49%, with positive and negative predictive values 38% and 83% respectively. Conclusions: Accessory renal arteries were markedly over-represented in resistant hypertensives compared with healthy controls. While not all patients with accessory arteries were nonresponders, nonresponse was related to both the presence and non-treatment of accessory arteries. Addressing accessory renal arteries in

  16. Association of Insulin Resistance, Arterial Stiffness and Telomere Length in Adults Free of Cardiovascular Diseases.

    Directory of Open Access Journals (Sweden)

    Irina Strazhesko

    Full Text Available Chronic inflammation and oxidative stress might be considered the key mechanisms of aging. Insulin resistance (IR is a phenomenon related to inflammatory and oxidative stress. We tested the hypothesis that IR may be associated with cellular senescence, as measured by leukocyte telomere length (LTL, and arterial stiffness (core feature of arterial aging, as measured by carotid-femoral pulse wave velocity (c-f PWV.The study group included 303 subjects, mean age 51.8 ±13.3 years, free of known cardiovascular diseases and regular drug consumption. For each patient, blood pressure was measured, blood samples were available for biochemical parameters, and LTL was analyzed by real time q PCR. C-f PWV was measured with the help of SphygmoCor. SAS 9.1 was used for statistical analysis.Through multiple linear regression analysis, c-f PWV is independently and positively associated with age (p = 0.0001 and the homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.0001 and independently negatively associated with LTL (p = 0.0378. HOMA-IR seems to have a stronger influence than SBP on arterial stiffness. In all subjects, age, HOMA-IR, LTL, and SBP predicted 32% of the variance in c-f PWV. LTL was inversely associated with HOMA-IR (p = 0.0001 and age (p = 0.0001. In all subjects, HOMA-IR, age, sex, and SBP predicted 16% of the variance in LTL.These data suggest that IR is associated with cell senescence and arterial aging and could, therefore, become the main target in preventing accelerated arterial aging, besides blood pressure control. Research in telomere biology may reveal new ways of estimating cardiovascular aging and risk.

  17. Effect of beta-adrenergic blockade on elevated arterial compliance and low systemic vascular resistance in cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Bendtsen, F; Henriksen, Jens Henrik Sahl

    2001-01-01

    investigation with determination of splanchnic and systemic haemodynamics. Arterial compliance was determined as the ratio of the stroke volume to the pulse pressure and compared to normal values. RESULTS: All the patients had significant portal hypertension, with a mean hepatic venous pressure gradient (HVPG......BACKGROUND: Patients with cirrhosis exhibit a characteristic hyperdynamic circulation with increased cardiac output and heart rate and reduced systemic vascular resistance. The compliance of the arterial tree has recently been reported to be increased in these patients, who are often treated...... systemic vascular resistance increased substantially (1083 versus 1378 dyn x s x cm-5, +27%; P arterial blood pressure (-6%; P

  18. Association between intrarenal arterial resistance and diastolic dysfunction in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Matthews D Geoffrey

    2008-05-01

    Full Text Available Abstract Background In comparison to the well established changes in compliance that occur at the large vessel level in diabetes, much less is known about the changes in compliance of the cardiovascular system at the end-organ level. The aim of this study was therefore to examine whether there was a correlation between resistance of the intrarenal arteries of the kidney and compliance of the left ventricle, as estimated by measurements of diastolic function, in subjects with type 2 diabetes. Methods We studied 167 unselected clinic patients with type 2 diabetes with a kidney duplex scan to estimate intrarenal vascular resistance, i.e. the resistance index (RI = peak systolic velocity-minimum diastolic velocity/peak systolic velocity and a transthoracic echocardiogram (TTE employing tissue doppler studies to document diastolic and systolic ventricular function. Results Renal RI was significantly higher in subjects with diastolic dysfunction (0.72 ± 0.05 when compared with those who had a normal TTE examination (0.66 ± 0.06, p Conclusion Increasing vascular resistance of the intrarenal arteries was associated with markers of diastolic dysfunction in subjects with type 2 diabetes. These findings are consistent with the hypothesis that vascular and cardiac stiffening in diabetes are manifestations of common pathophysiological mechanisms.

  19. Effect of Acute Resistance Exercise on Carotid Artery Stiffness and Cerebral Blood Flow Pulsatility

    Directory of Open Access Journals (Sweden)

    Wesley K Lefferts

    2014-03-01

    Full Text Available Arterial stiffness is associated with cerebral flow pulsatility. Arterial stiffness increases following acute resistance exercise (RE. Whether this acute RE-induced vascular stiffening affects cerebral pulsatility remains unknown. Purpose: To investigate the effects of acute RE on common carotid artery (CCA stiffness and cerebral blood flow velocity (CBFv pulsatility. Methods: Eighteen healthy men (22 ± 1 yr; 23.7 ± 0.5 kg∙m-2 underwent acute RE (5 sets, 5-RM bench press, 5 sets 10-RM bicep curls with 90 s rest intervals or a time control condition (seated rest in a randomized order. CCA stiffness (β-stiffness, Elastic Modulus (Ep and hemodynamics (pulsatility index, forward wave intensity and reflected wave intensity were assessed using a combination of Doppler ultrasound, wave intensity analysis and applanation tonometry at baseline and 3 times post-RE. CBFv pulsatility index was measured with transcranial Doppler at the middle cerebral artery (MCA. Results: CCA β-stiffness, Ep and CCA pulse pressure significantly increased post-RE and remained elevated throughout post-testing (p 0.05. There were significant increases in forward wave intensity post-RE (p0.05. Conclusion: Although acute RE increases CCA stiffness and pressure pulsatility, it may not affect CCA or MCA flow pulsatility. Increases in pressure pulsatility may be due to increased forward wave intensity and not pressure from wave reflections.

  20. Repeated cessation and resumption of resistance training attenuates increases in arterial stiffness.

    Science.gov (United States)

    Okamoto, T; Sakamaki, M S; Min, S K; Yoshida, S; Watanabe, Y; Ogasawara, R

    2015-06-01

    Although high-intensity resistance training (RT) increases arterial stiffness, removing weightlifting stimuli returns arterial stiffness to baseline levels within relatively short periods during 4-8 weeks. This study investigates the effects of repeated RT cessation and resumption on arterial stiffness. Eighteen young healthy subjects were randomly assigned to a group that performed continuous RT (CRT, n=9) and a group that performed periodic RT (PRT, n=9). Both groups performed RT at 75% of one repetition maximum for 3 days per week. The CRT group continuously trained for 16 weeks, whereas the PRT group performed 3 cycles of 4 weeks training, with 2 weeks detraining intervals between cycles. The carotid-femoral pulse wave velocity in the CRT group significantly increased (Pstrength in the both groups significantly increased after 16 weeks from baseline and persisted for 20 weeks (P<0.05). These results suggest that PRT, including short-term repeated cessation and resumption, attenuates increases in arterial stiffness. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?

    Science.gov (United States)

    Kirikoshi, Hiroyuki; Yoneda, Masato; Mawatari, Hironori; Fujita, Koji; Imajo, Kento; Kato, Shingo; Suzuki, Kaori; Kobayashi, Noritoshi; Kubota, Kensuke; Maeda, Shin; Nakajima, Atsushi; Saito, Satoru

    2012-01-01

    AIM: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) resistant to transarterial chemoembolization (TACE). METHODS: This study was conducted on 42 patients who received HAIC for advanced HCC between 2001 and 2010 at our hospital. 5-fluorouracil (5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir. Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU. The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010 (written in Japanese); one group of patients who did not fulfill the criteria for TACE resistance (group A, n = 23), and another group who fulfilled the criteria for TACE resistance (group B, n = 19). We compared the outcomes in terms of the response and survival rates between the two groups. RESULTS: Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B (response rate: 48% vs 16%, P = 0.028, tumor suppression rate: 87% vs 53%, P = 0.014). Furthermore, both the progression-free survival rate and survival time were significantly superior in group A than in group B (3-, 6-, 12-, and 24-mo = 83%, 70%, 29% and 20% vs 63%, 42%, 16% and 0%, respectively, P = 0.040, and 9.8 mo vs 6.2 mo, P = 0.040). A multivariate analysis (Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival (P = 0.007). CONCLUSION: HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE. Other tools for treatment, i.e., molecular-targeting agents may be considered for these cases. PMID:22563174

  2. Superoxide dismutase entrapped-liposomes restore the impaired endothelium-dependent relaxation of resistance arteries in experimental diabetes.

    Science.gov (United States)

    Voinea, Manuela; Georgescu, Adriana; Manea, Adrian; Dragomir, Elena; Manduteanu, Ileana; Popov, Doina; Simionescu, Maya

    2004-01-19

    Diabetes is associated with impaired endothelium-dependent relaxation. We questioned whether administration of superoxide dismutase (superoxide: superoxide oxidoreductase, EC 1.15.1.1) entrapped in long-circulating liposomes improves the vascular reactivity of the resistance arteries. Using the myograph technique, the vasodilation in response to acetylcholine was measured in mesenteric resistance arteries isolated from diabetic or normal hamsters treated for 3 days with superoxide dismutase entrapped in liposomes, with the same concentrations of free superoxide dismutase and plain liposomes, or untreated. Superoxide dismutase activity and nitric oxide (NO) levels were assayed by spectrophotometry, superoxide dismutase levels by Western blot and the role of N(pi)-nitro-L-arginine ethylester (L-NAME) on vasodilation by the myograph technique. Our data revealed that: (i) superoxide dismutase entrapped in liposomes restored to a great extent the endothelium-dependent relaxation of diabetic hamster resistance arteries; (ii) in superoxide dismutase entrapped in liposomes-treated diabetic animals, the activity and the level of superoxide dismutase in arterial homogenates as well as the serum nitrite levels were significantly higher than those in untreated hamsters or hamsters treated with free superoxide dismutase and plain liposomes: (iii) L-NAME inhibited the response of arteries to acetylcholine in superoxide dismutase entrapped in liposomes-treated diabetic hamsters. These results suggest that superoxide dismutase entrapped in liposomes is effective in scavenging superoxide anions, increases nitric oxide bioactivity and improves the vasorelaxation of resistance arteries in diabetic hamsters.

  3. Distensibility of portacaval shunts in portal hypertensive cats: index of contractility model.

    Science.gov (United States)

    Inglés, A C; Legare, D J; Lautt, W W

    1994-06-01

    Complete shunting of portal blood flow through portacaval shunts was obtained using a constrictor around the portal vein to gradually produce a total occlusion. After 4 weeks, acute experiments were conducted in anesthetized cats. Blood from the femoral artery was shunted through a pump to supply and control the entire portal blood flow. As shunted portal blood flow was varied over a wide range, the portal shunt resistance showed distensibility. Decreasing portal venous pressure from 15.0 +/- 0.9 to 11.1 +/- 0.6 mmHg (1 mmHg = 133.3 Pa) resulted in elevations of resistance of 58%. The relation between the resistance (R) and the distending pressure (Pd) was a constant, the index of contractility (IC), where IC = R.Pd3. In steady state, the IC was 485 +/- 55 mmHg4.mL-1.min.kg and did not change passively in response to changes in portal blood flow. In conclusion, portacaval shunts are passively distensible, and resistance is altered as a cubic function of the distending pressure. Because resistance is altered both actively and passively, the IC should prove useful to differentiate these alternatives for evaluation of changes in portal hypertensive therapy.

  4. Intra-arterial papaverine and leg vascular resistance during in situ bypass surgery with high or low epidural anaesthesia

    DEFF Research Database (Denmark)

    Rørdam, Peter; Jensen, Leif Panduro; Schroeder, T V

    1993-01-01

    In situ saphenous vein arterial bypass flow was studied in 16 patients with respect to level of epidural anaesthesia. Arterial pressure and electromagnetic flow were used to evaluate arterial tone by intra-arterial (i.a.) papaverine. Eight patients had a low epidural block (... patients were operated during high epidural anaesthesia (> Th. 10). Flow increased and arterial pressure decreased after i.a. papaverine in all patients. When compared with patients operated during high epidural anaesthesia, flow increase and decrease in vascular resistance took place in patients operated...... during low epidural anaesthesia (P i.a. papaverine was not significantly different in patients operated in low epidural and general anaesthesia (n = 8). In eight patients with insulin-dependent diabetes mellitus who had low epidural anaesthesia, the increase...

  5. Expression of connexin 37, 40 and 43 in rat mesenteric arterioles and resistance arteries

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Mikkelsen, Hanne B; Arensbak, Birgitte

    2003-01-01

    Connexins are the protein constituents of gap junctions which mediate intercellular communication in most tissues. In arterioles gap junctions appear to be important for conduction of vasomotor responses along the vessel. Studies of the expression pattern of connexin isoforms in the microcirculat......Connexins are the protein constituents of gap junctions which mediate intercellular communication in most tissues. In arterioles gap junctions appear to be important for conduction of vasomotor responses along the vessel. Studies of the expression pattern of connexin isoforms...... in the microcirculation are sparse. We investigated the expression of the three major vascular connexins in mesenteric arterioles (diameter micro m) from male Sprague-Dawley rats, since conducted vasomotor responses have been described in these vessels. The findings were compared with those obtained from upstream...... small resistance arteries. Indirect immunofluorescence techniques were used on whole mounts of mesenteric arterioles and on frozen sections of resistance arteries (diameter approximately 300 micro m). Mesenteric arterioles expressed Cx40 and Cx43 in the endothelial layer, and Cx37 was found in most...

  6. Acute Ethanol Intake Induces NAD(PH Oxidase Activation and Rhoa Translocation in Resistance Arteries

    Directory of Open Access Journals (Sweden)

    Janaina A. Simplicio

    Full Text Available Abstract Background: The mechanism underlying the vascular dysfunction induced by ethanol is not totally understood. Identification of biochemical/molecular mechanisms that could explain such effects is warranted. Objective: To investigate whether acute ethanol intake activates the vascular RhoA/Rho kinase pathway in resistance arteries and the role of NAD(PH oxidase-derived reactive oxygen species (ROS on such response. We also evaluated the requirement of p47phox translocation for ethanol-induced NAD(PH oxidase activation. Methods: Male Wistar rats were orally treated with ethanol (1g/kg, p.o. gavage or water (control. Some rats were treated with vitamin C (250 mg/kg, p.o. gavage, 5 days before administration of water or ethanol. The mesenteric arterial bed (MAB was collected 30 min after ethanol administration. Results: Vitamin C prevented ethanol-induced increase in superoxide anion (O2- generation and lipoperoxidation in the MAB. Catalase and superoxide dismutase activities and the reduced glutathione, nitrate and hydrogen peroxide (H2O2 levels were not affected by ethanol. Vitamin C and 4-methylpyrazole prevented the increase on O2- generation induced by ethanol in cultured MAB vascular smooth muscle cells. Ethanol had no effect on phosphorylation levels of protein kinase B (Akt and eNOS (Ser1177 or Thr495 residues or MAB vascular reactivity. Vitamin C prevented ethanol-induced increase in the membrane: cytosol fraction ratio of p47phox and RhoA expression in the rat MAB. Conclusion: Acute ethanol intake induces activation of the RhoA/Rho kinase pathway by a mechanism that involves ROS generation. In resistance arteries, ethanol activates NAD(PH oxidase by inducing p47phox translocation by a redox-sensitive mechanism.

  7. Impaired recovery of intracellular calcium and force after activation in isolated myometrial and subcutaneous resistance arteries from women with preeclampsia.

    Science.gov (United States)

    Wimalasundera, Ruwan C; Wijetunge, Sumangali; Thom, Simon M; Regan, Lesley; Hughes, Alun D

    2010-03-01

    Preeclampsia is a major cause of maternal and perinatal morbidity and mortality, but its cause is poorly understood. This study investigated whether there is an abnormality of intracellular calcium ([Ca2=]i) and tension during recovery from activation in isolated resistance arteries in preeclampsia and investigated the underlying mechanisms. Subcutaneous and myometrial resistance arteries from preeclamptic, normotensive pregnant and nonpregnant women were mounted on an isometric myograph and loaded with fura-2 to allow simultaneous measurement of force and [Ca2+]i. Arteries were activated by a high-potassium solution or noradrenaline, and the rate of decline in force and [Ca2+]i examined following washout. Basal tone and [Ca2+]i and rise in force and [Ca2+]i induced by high-potassium solution did not differ between groups but the rate of decline after washout was significantly slowed in both subcutaneous and myometrial arteries from preeclamptic women as compared with normotensive pregnant or nonpregnant women. The rate of decline in force after noradrenaline was also slowed in arteries from preeclamptic women. In subcutaneous resistance arteries from nonpregnant women, removal of the endothelium did not affect the rate of decline in force after high-potassium solution. However, inhibition of the plasma membrane Ca ATPase with carboxyeosin mimicked the findings seen in preeclampsia. In contrast, inhibition of the sarcoplasmic endoreticulum Ca ATPase with cyclopiazonic acid had no effect on the rate of decline in force or [Ca2+]i. The rate of relaxation and decline in [Ca2+]i in resistance arteries are impaired in preeclampsia. This may be mediated by decreased activity of plasma membrane Ca2+ ATPase and could be a mechanism contributing to elevated peripheral resistance and raised blood pressure in preeclampsia.

  8. AORTIC POST-RESISTANCE EXERCISE HYPOTENSION IN PATIENTS WITH PERIPHERAL ARTERY DISEASE

    Directory of Open Access Journals (Sweden)

    Marilia de Almeida Correia

    Full Text Available ABSTRACT Introduction: A single session of resistance training decreases brachial blood pressure (BP in patients with peripheral artery disease (PAD. However, it is not known whether similar responses occur in aortic BP, which is a better predictor of cardiovascular risk. Objective: This study aimed to analyze the effects of a single session of resistance training on aortic BP in PAD patients. Methods: This randomized, crossover, controlled trial involved 16 patients. All of them performed a session of resistance training (R - 3 x 10 reps in eight exercises, 5-7 on the OMNI Scale and a control session (C - resting for 50 min. Before and after each session, aortic BP was assessed by applanation tonometry technique. Results: There was an increase in systolic (P<0.002 and mean (P<0.001 aortic BP in both sessions; however, higher increases were observed in C session (P<0.001. Additionally, diastolic aortic BP only increased after C session (P=0.004. The hypotensive effect of the exercise on systolic, diastolic, and mean aortic BP were -12±2, -6±2, and -7±2 mmHg, respectively. Conclusion: A single session of resistance training promoted a hypotensive effect on aortic BP of patients with PAD, indicating an acute reduction in cardiovascular risk in this population. Level of Evidence I; Therapeutic studies - Investigating the results of treatment.

  9. Low-intensity resistance exercise does not affect cardiac autonomic modulation in patients with peripheral artery disease

    Directory of Open Access Journals (Sweden)

    Aluísio H.R. Andrade Lima

    2013-05-01

    Full Text Available OBJECTIVE: To analyze the effect of a single bout of resistance exercise on cardiac autonomic modulation in patients with peripheral artery disease. METHODS: Fifteen patients with peripheral artery disease (age: 58.3±4.0 years underwent the following sessions in a random order: resistance exercise (three sets of 10 repetitions of the six resistance exercises with a workload of 5-7 in the OMNI-RES scale and control (similar to the resistance session; however, the resistance exercises were performed with no load. The frequency domain (low frequency, high frequency and sympathovagal balance and symbolic analysis (0V, 1V and 2V patterns of heart rate variability were obtained before and until one hour after the interventions. RESULTS: After the resistance exercise and control sessions, similar increases were observed in the consecutive heartbeat intervals (control: 720.8±28.6 vs. 790.9±34.4 ms; resistance exercise: 712.9±30.1 vs. 756.8±37.9 ms; p0.05. CONCLUSION: A single bout of resistance exercise did not alter cardiac autonomic modulation in patients with peripheral artery disease.

  10. The pulsatility index and the resistive index in renal arteries in patients with hypertension and chronic renal failure

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Ladefoged, S D

    1995-01-01

    The pulsatility index (PI) and the resistive index (RI) are used as pulsed-wave Doppler measurement of downstream renal artery resistance. Little information is available on their value in chronic renal failure and their correlation to parameters of renal function and haemodynamics. The aim...... was to compare PI and RI of renal arteries in healthy volunteers and in patients with hypertension and chronic renal failure, and furthermore to study the correlation of these indices to measurements of renal haemodynamics and function by standard methods in patients with renal failure and hypertension....

  11. Potential Biomarkers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Sharifah Intan Qhadijah Syed Ikmal

    2013-01-01

    Full Text Available Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to assess the progression of atherosclerosis and inflammation. Along with coronary arterial damage and inflammatory processes, high-sensitivity C-reactive protein is considered as an essential atherosclerosis marker in patients with cardiovascular disease, but not as an insulin resistance marker in type 2 diabetes mellitus patients. A new biological marker that can act as a reliable indicator of both the exact state of insulin resistance and atherosclerosis is required to facilitate optimal health management of diabetic patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads to innate immune activation and released several biological markers into circulation. This review examines potential biological markers, YKL-40, alpha-hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding protein-4, and chemerin, as they may play significant roles in insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.

  12. Potential biomarkers of insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.

    Science.gov (United States)

    Syed Ikmal, Sharifah Intan Qhadijah; Zaman Huri, Hasniza; Vethakkan, Shireene Ratna; Wan Ahmad, Wan Azman

    2013-01-01

    Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to assess the progression of atherosclerosis and inflammation. Along with coronary arterial damage and inflammatory processes, high-sensitivity C-reactive protein is considered as an essential atherosclerosis marker in patients with cardiovascular disease, but not as an insulin resistance marker in type 2 diabetes mellitus patients. A new biological marker that can act as a reliable indicator of both the exact state of insulin resistance and atherosclerosis is required to facilitate optimal health management of diabetic patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads to innate immune activation and released several biological markers into circulation. This review examines potential biological markers, YKL-40, alpha-hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding protein-4, and chemerin, as they may play significant roles in insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.

  13. Arterial stiffness and blood flow adaptations following eight weeks of resistance exercise training in young and older women.

    Science.gov (United States)

    Rossow, Lindy M; Fahs, Christopher A; Thiebaud, Robert S; Loenneke, Jeremy P; Kim, Daeyeol; Mouser, James G; Shore, Erin A; Beck, Travis W; Bemben, Debra A; Bemben, Michael G

    2014-05-01

    Resistance training is recommended for all adults of both sexes. The arterial stiffness and limb blood flow responses to resistance training in young and older women have not been well-studied. The purpose of this study was to examine arterial stiffness and blood flow adaptations to high-intensity resistance exercise training in young and older women. Young (aged 18-25) and older (aged 50-64) women performed full-body high-intensity resistance exercise three times per week for eight weeks. The following measurements were performed twice prior to training and once following training: carotid to femoral and femoral to tibialis posterior pulse wave velocity (PWV), blood pressure, heart rate, resting forearm blood flow and forearm reactive hyperemia. Data was analyzed by ANOVAs with alpha set at 0.05. Correlations were also examined between changes in arterial stiffness and baseline arterial stiffness values. Older subjects had higher carotid-femoral PWV than younger subjects. No significant effects were found for femoral-tibialis posterior PWV or for resting forearm blood flow. Changes in carotid-femoral and femoral-tibialis posterior PWV correlated significantly with their respective baseline values. Older subjects increased peak forearm blood flow while young subjects showed no change. Total hyperemia increased significantly in both groups. In conclusion, in both young and older women, eight weeks of high-intensity resistance training appeared to improve microvascular forearm function while not changing carotid-femoral or femoral-tibialis posterior arterial stiffness. However, a large degree of individual variation was found and arterial stiffness adaptations appeared positively related to the initial stiffness values. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. The role of peripheral vascular resistance in determining the infrainguinal arterial reconstruction patency.

    Science.gov (United States)

    Cheshmedzhiev, Mihail V; Knyazhev, Victor V; Radev, Radoslav S; Yordanov, Emil D

    2011-01-01

    To find if there is any correlation between the peripheral vascular resistance, its change following an intragraft prostaglandin infusion and the infrainguinal reconstruction patency. Ninety-seven patients with infrainguinal reconstructions were included in the study: in 48 patients they were compromised (32 with graft thrombosis and 16 with stenosis of the distal anastomoses); 49 patients had their bypasses patent for no less than 12 months. Intraoperative flowmetry was performed on the target artery under the distal anastomosis, after declamping, and after a five-minute intragraft prostaglandin infusion. We measured the peripheral vascular resistance (PVR) by two methods - as a ratio of the invasively measured average pressure to the average blood flow volume (mmHg/ml/min. = peripheral resistance unit [PRU]) and by using the readings by the flowmeter (ohms). The decrease of peripheral resistance was calculated in the functioning and the compromised reconstructions after administration of prostaglandin. We found that if PVR decreases 4.5 times (in ohms) the prognosis is good; we can make the same positive prognosis when the ratio of the mean invasively measured pressure to the mean blood flow volume (Pmean/Qmean) decreases more than four times. Values greater than 1.07 ohms, after peripheral vasodilatation, are indicative of high peripheral vascular resistance, at a level of specificity of 86%, and values greater than 0.57 PRU - at a level of specificity of 87%. Although PVR measurements cannot predict with absolute certainty that bypasses under the inguinal ligament shall stay patent for a long time, it is a valuable indicator showing the immediate outcome of reconstruction work carried out with the patient on the operating table. Finding Any technical errors and dealing with them saves time and money, as well as prevents the stress on the part of patients caused by the required additional revisions and multiple operations.

  15. Prolonged bed rest impairs rapid CPI-17 phosphorylation and contraction in rat mesenteric resistance arteries to cause orthostatic hypotension.

    Science.gov (United States)

    Kitazawa, Toshio; Kitazawa, Kazuyo

    2017-12-01

    Prolonged bed rest (PBR) causes orthostatic hypotension (OH). Rapid constriction of splanchnic resistance arteries in response to a sudden increase in sympathetic tone contributes to the recovery of orthostatic arterial pressure upon standing. However, the molecular mechanism of PBR-induced dysfunction in arterial constriction is not fully understood. Previously, we showed that CPI-17, a regulatory protein for myosin phosphatase, mediates α 1A -adrenergic receptor-induced rapid contraction of small mesenteric arteries. Here, we tested whether PBR associated with OH affects the α 1 -adrenergic receptor-induced CPI-17 signaling pathway in mesenteric arteries using rats treated by head-down tail-suspension hindlimb unloading (HDU), an experimental OH model. In normal anesthetized rats, mean arterial pressure (MAP) rapidly reduced upon 90° head-up tilt from supine position and then immediately recovered without change in heart rate, suggesting a rapid arterial constriction. On the other hand, after a 4-week HDU treatment, the fast orthostatic MAP recovery failed for 1 min. Alpha1A subtype-specific antagonist suppressed the orthostatic MAP recovery with a small decrease in basal blood pressure, whereas non-specific α 1 -antagonist prazosin strongly reduced both basal MAP and orthostatic recovery. The HDU treatment resulted in 68% reduction in contraction in parallel with 83% reduction in CPI-17 phosphorylation in denuded mesenteric arteries 10 s after α 1 -agonist stimulation. The treatment with either Ca 2+ -release channel opener or PKC inhibitor mimicked the deficiency in HDU arteries. These results suggest that an impairment of the rapid PKC/CPI-17 signaling pathway downstream of α 1A -adrenoceptors in peripheral arterial constriction, as an end organ of orthostatic blood pressure reflex, is associated with OH in prolonged bed rest patients.

  16. Assessment of the effect of radio contrast media on resistive index of renal artery by color doppler sonography

    International Nuclear Information System (INIS)

    Shakourirad, Ali; Ataeefar Mehdi; Jozaghi, Solmaz

    2009-01-01

    Renal ischemia and direct toxic effect of contrast media are the main confounding causes of contrast-induced nephropathy (CIN). The effect of different contrast mediums on the resistance of renal artery is quite unclear. The aim of the present study was to assess the resistive index (RI) changes of renal segmental artery in color Doppler duplex sonography after injection of two different contrast mediums: iodixanol and iohexol. The RI of the renal segmental artery of 62 randomly chosen patients, with a normal baseline renal function, was calculated using color-coded Doppler sonography before and five minutes after bolus injection of two different contrast mediums. Thirty-one patients were administered 50 mL of iodixanol (Visipaque) and 31 patients were administered 50 mL of iohexol (Omnipaque) during intravenous urogram procedures. The RI results were analyzed and compared in two groups using two-tailed t-test. The mean RI of renal segmental artery increased significantly after administration of contrast media (mean + - SD 0.61 + - 0.046 vs 0.58 +- 0.042; p< 0.001). The mean change of RI was 0.0387 +- .00552 (mean + - SE) in the setting of iohexol injection and 0.0216 + - .00423 (mean + - SE) five minutes after administration of iodixanol (p0.017). Both non-ionic iso-osmolar dimeric iodixanol and low-osmolar iohexol increase the renal artery resistance, but the changes are more dramatic with iohexol, suggesting better tolerance with iodixanol. (author)

  17. Hemodynamic Responses to Resistance Exercise in Patients with Coronary Artery Disease.

    Science.gov (United States)

    Gjøvaag, Terje F; Mirtaheri, Peyman; Simon, Kristoffer; Berdal, Gøran; Tuchel, Irja; Westlie, Tonje; Bruusgaard, Kari Anette; Nilsson, Birgitta Blakstad; Hisdal, Jonny

    2016-04-01

    Investigate hemodynamic responses of resistance exercise (RE) with moderate load (i.e., international guidelines for RE of patients) versus RE with high load in patients with coronary artery disease (CAD). Medically stable male (n = 11) and female patients (n = 4) treated with PCI or percutaneous coronary intervention, or coronary artery bypass surgery a minimum of 6 months before this study, performed three sets of 15RM and 4RM RE in a randomized order on separate days. Beat-to-beat systolic (SBP), diastolic (DBP) blood pressure, heart rate (HR), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR) were monitored at preexercise, and continuously during RE. Compared with preexercise, SBP and DBP (mean of three sets) increased by 12% to 13% (both; P < 0.001) and 35% to 40% after 15RM RE (both; P < 0.001). 15RM SBP and DBP were higher than 4RM SBP and DBP (both; P < 0.001). The SBP of the fourth repetition of 15 RM RE was similar to the SBP of the fourth repetition of 4RM RE. Compared with preexercise, SV increased moderately after 4RM and 15 RM RE, respectively (both, P < 0.001). HR increased more after 15RM compared with 4RM RE (P < 0.05); thus, higher CO after 15RM (compared with 4RM RE; P < 0.05) was mainly caused by higher HR. SVR decreased by 15% (P < 0.001) and 50% (P < 0.01) after 4RM and 15RM RE. SBP and DBP increased significantly more during moderate load RE; thus, the magnitude of the external load is not the prime determinant of the pressure response during RE. If management of blood pressure is of concern, high load/low rep RE is preferable to medium load/high rep RE.

  18. Relaxing Responses to Hydrogen Peroxide and Nitric Oxide in Human Pericardial Resistance Arteries Stimulated with Endothelin-1

    DEFF Research Database (Denmark)

    Leurgans, Thomas M; Bloksgaard, Maria; Irmukhamedov, Akhmadjon

    2018-01-01

    In human pericardial resistance arteries, effects of the endothelium-dependent vasodilator bradykinin are mediated by NO during contraction induced by K(+) or the TxA2 analogue U46619 and by H2 O2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces...... relaxing effects of NO and increases those of H2 O2 in resistance artery smooth muscle of patients with cardiovascular disease. Arterial segments, dissected from the parietal pericardium of 39 cardiothoracic surgery patients, were studied by myography during amplitude-matched contractions induced by K......(+) , the TXA2 analogue U46619 or ET-1. Effects of the NO-donor Na-nitroprusside (SNP) and of exogenous H2 O2 were recorded in absence and presence of inhibitors of cyclooxygenases, NO-synthases and small and intermediate conductance calcium-activated K(+) channels. During contractions induced by either...

  19. Effects of oophorectomy on functional properties of resistance arteries isolated from the cancellous bone of the rabbit femur

    DEFF Research Database (Denmark)

    Hansen, Vibeke Brogaard; Forman, A; Lundgaard, Anette

    2001-01-01

    Information is sparse concerning the effect of oophorectomy (OOX) on bone vascularization and blood flow of possible significance for altered remodeling. Whether OOX affects functional characteristics of isolated bone resistance arteries was investigated. Ring preparations (diameter approximately...... 250 microm) of small femoral bone arteries from oophorectomized and sham-operated rabbits were mounted on a myograph six weeks postoperatively. Cumulative concentration response curves were obtained for various agonists at a normalized lumen diameter. Oophorectomy did not significantly influence lumen...... regional differences in the effects of OOX on small arteries of importance for control of vascular resistance in bone which suggests a relation between altered vascular function after ovarian hormonal withdrawal and the changes in bone turnover associated with osteoporosis....

  20. Contractile Changes in the Vasculature After Subchronic Smoking

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Kruse, Lars Schack; Johansson, Helle Wulf

    2016-01-01

    INTRODUCTION: Cigarette smoking is a well-known risk factor for developing cardiovascular diseases, but the underlying mechanisms are largely unknown. Recent data suggest that vasocontractile receptor modulation could be an important factor. Surfactant protein D (SP-D) is important in the particle...... clearance in the lungs and knock-out (KO) mice for this protein develop emphysema. SP-D is also weakly expressed in the vasculature. We aimed to investigate whether SP-D was important in the cardiovascular response to cigarette smoke exposure (CSE), by utilizing SP-D KO mice and a myograph setup. METHODS......: Wild type (WT) and SP-D KO mice were exposed to cigarette smoke (CS) or room air for 12 weeks. The pulmonary artery, left anterior descending coronary artery, and basilar artery (BA) were isolated and mounted in wire myographs. Contractile concentration response curves to endothelin-1 and UDP were...

  1. Synergism of diabetic and inflammatory culture conditions on reactivity of isolated small arteries

    DEFF Research Database (Denmark)

    Blædel, Martin Mads; Boonen, Harrie C.M.; Sams Nielsen, Anette

    Background: Cardiovascular disease (CVD) is the manifestation of atherosclerosis, which has been linked to obesity, the metabolic syndrome (MS) and overt type 2 diabetes (T2DM). Vascular dysfunction has been proposed to precede atherosclerosis, and in addition, a correlation between vascular...... dysfunction and local vascular inflammation has been suggested. Aim: This study addresses the involvement of vascular risk factors of MS and T2DM such as elevated glucose, increased insulin levels, as well as selected cytokines on vascular contractile function. Methods: Small mesenteric resistance arteries...... isolated from 8 week old male SD rats were cultured for 21 hours in Endothelial Basal Medium (EBM-2) in petri dishes and in the absence or presence of either 30 mM D-glucose, 100 nM insulin, 100 ng/mL TNFa or any combination of these. Contractile reactivity of normalised arteries was then determined...

  2. Effects of minoxidil and nitroprusside on reflex increases in myocardial contractility.

    Science.gov (United States)

    Robie, N W

    1978-01-01

    1 The effects of nitroprusside and minoxidil on increases in myocardial contractility resulting from carotid artery occlusion were investigated in anaesthetized dogs. The results were compared with those produced by intravenous influsion of noradrenaline. 2 Nitroprusside and minoxidil attenuated the pressor responses produced by carotid artery occlusion. 3 Nitroprusside, but not minoxidil, attenuated the maximal myocardial contractility resulting from carotid occlusion. 4 The pressor and contractility responses to noradrenaline infusion were unaffected by either agent. 5 Nitroprusside failed to alter the myocardial responses produced by dimethylphenylpiperazinium. 6 These results, in conjunction with those of other investigators who have demonstrated that nitroprusside does not affect the release of noradrenaline from adrenergic neurons, suggest that nitroprusside may inhibit sympathetic nervous system reflex activity via an afferent and/or central component. PMID:620094

  3. Clinical Outcomes of Transcatheter Arterial Embolization for Adhesive Capsulitis Resistant to Conservative Treatment.

    Science.gov (United States)

    Okuno, Yuji; Iwamoto, Wataru; Matsumura, Noboru; Oguro, Sota; Yasumoto, Taku; Kaneko, Takao; Ikegami, Hiroyasu

    2017-02-01

    To evaluate clinical outcomes of transcatheter arterial embolization (TAE) for adhesive capsulitis resistant to conservative treatments. This study comprised 25 patients (18 women and 7 men; mean age, 53.8 y; range, 39-68 y) with adhesive capsulitis resistant to conservative treatments. TAE was performed, and adverse events (AEs), pain visual analog scale (VAS) score changes, range of motion (ROM), and American Shoulder and Elbow Surgeons (ASES) scores were assessed. Abnormal vessels were identified in all patients. No major AEs were associated with TAE. One patient was lost to follow-up. The remaining 24 patients were available for final follow-up (mean, 36.1 months; range, 30-44 months). Of the 24 patients, 16 (67%) experienced quick improvement of nighttime pain (ie, VAS scores decreased > 50% from baseline) within 1 week, and 21 (87%) improved within 1 month. In terms of mean overall pain (ie, pain at its worst), VAS scores significantly decreased at 1, 3, and 6 months after treatment (82 mm before treatment vs 52, 19, and 8 mm after treatment; P adhesive capsulitis that has failed to improve with conservative treatments. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  4. Effects of baroreflex activation therapy on arterial stiffness and central hemodynamics in patients with resistant hypertension.

    Science.gov (United States)

    Wallbach, M; Lehnig, Luca-Yves; Schroer, Charlotte; Helms, Hans-Joachim; Lüders, Stephan; Patschan, Daniel; Patschan, Susann; Müller, Gerhard A; Wachter, Rolf; Koziolek, Michael J

    2015-01-01

    High central blood pressure, augmentation index and pulse wave velocity are independent cardiovascular risk factors. Little is known of the effect of baroreflex activation therapy on central hemodynamics. In this prospective clinical trial, radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressure and hemodynamic indices (i.e. augmentation pressure, augmentation index, pulse wave velocity, systolic and diastolic pressure time integral, subendocardial viability index) at baseline and 6 months after starting baroreflex activation therapy in 25 patients with resistant hypertension. Apart from peripheral blood pressure reduction, 6 months of baroreflex activation therapy significantly reduced mean central aortic blood pressure from 109.7 ± 20.5 to 97.4 ± 18.8 mm Hg (P baroreflex activation therapy. Systolic pressure time integral was significantly reduced (P = 0.03), whereas subendocardial viability index remained unchanged. Apart from peripheral blood pressure, baroreflex activation therapy reduces central blood pressure, augmentation index at a heart rate of 75 b.p.m. and pulse wave velocity in patients with resistant hypertension, suggesting strong potential to reduce cardiovascular risk.

  5. Analysis of intimal proteoglycans in atherosclerosis-prone and atherosclerosis-resistant human arteries by mass spectrometry.

    Science.gov (United States)

    Talusan, Paul; Bedri, Shahinaz; Yang, Suping; Kattapuram, Taj; Silva, Nilsa; Roughley, Peter J; Stone, James R

    2005-09-01

    The propensity to develop atherosclerosis varies markedly among different sites in the human vasculature. To determine a possible cause for such differences in atherosclerosis susceptibility, a proteomics-based approach was used to assess the extracellular proteoglycan core protein composition of intimal hyperplasia from both the atherosclerosis-prone internal carotid artery and the atherosclerosis-resistant internal thoracic artery. The intimal proteoglycan composition in these preatherosclerotic lesions was found to be more complex than previously appreciated with up to eight distinct core proteins present, including the large extracellular proteoglycans versican and aggrecan, the basement membrane proteoglycan perlecan, the class I small leucine-rich proteoglycans biglycan and decorin, and the class II small leucine-rich proteoglycans lumican, fibromodulin, and prolargin/PRELP (proline arginine-rich end leucine-rich repeat protein). Although most of these proteoglycans seem to be present in similar amounts at the two locations, there was a selective enhanced deposition of lumican in the intima of the atherosclerosis-prone internal carotid artery compared with the intima of the atherosclerosis-resistant internal thoracic artery. The enhanced deposition of lumican in the intima of an atherosclerosis prone artery has important implications for the pathogenesis of atherosclerosis.

  6. The pulsatility index and the resistive index in renal arteries. Associations with long-term progression in chronic renal failure

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Talleruphuus, U

    1997-01-01

    The pulsatility index (PI) and the resistive index (RI) are used as pulsed-wave Doppler measurements of downstream renal artery resistance. PI and RI have been found to correlate with renal vascular resistance, filtration fraction and effective renal plasma flow in chronic renal failure. The aim...... of the present study was to evaluate the potential relationship between these indices and the rate of decline in renal function, as reflected by changes in different parameters of renal function in patients with chronic renal failure....

  7. [Contractile function of the heart and myocardium antioxidant system in rats of August and Wistar strains during ischemia and reperfusion].

    Science.gov (United States)

    Sazontova, T G; Belkina, L M; Zhukova, A G; Kirillina, T N; Arkhipenko, Iu V

    2004-01-01

    In August rats, local myocardial ischemia caused by 30-min occlusion of the coronary artery induced a slight depression of the contractile function of the heart; the latter was restored after 15-min reperfusion more rapidly than in Wistar rats. In August rats, the activities of antioxidant protection enzymes were lower than in Wistar rats. In comparison with Wistar rats, these enzyme activities were decreased in a lesser degree under ischemia and were restored in a greater degree under reperfusion. It may thus be concluded that the higher stability of antiradical protection parameters in August rats is one of the mechanisms responsible for the enhanced resistance of the heart to ischemia- and reperfusion-induced injuries.

  8. Corrosion resistance improvement for 316L stainless steel coronary artery stents by trimethylsilane plasma nanocoatings.

    Science.gov (United States)

    Eric Jones, John; Chen, Meng; Yu, Qingsong

    2014-10-01

    To improve their corrosion resistance and thus long-term biocompatibility, 316L stainless steel coronary artery stents were coated with trimethylsilane (TMS) plasma coatings of 20-25 nm in thickness. Both direct current (DC) and radio-frequency (RF) glow discharges were utilized for TMS plasma coatings and additional NH₃/O₂ plasma treatment to tailor the surface properties. X-ray photoelectron spectroscopy (XPS) was used to characterize the coating surface chemistry. It was found that both DC and RF TMS plasma coatings had Si- and C-rich composition, and the O- and N-contents on the surfaces were substantially increased after NH₃/O₂ plasma treatment. Surface contact angle measurements showed that DC TMS plasma nanocoating with NH₃/O₂ plasma treatment generated very hydrophilic surface. The corrosion resistance of TMS plasma coated stents was evaluated through potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. The potentiodynamic polarization demonstrated that the TMS plasma coated stents imparted higher corrosion potential and pitting potential, as well as lower corrosion current densities as compared with uncoated controls. The surface morphology of stents before and after potentiodynamic polarization testing was analyzed with scanning electron microscopy, which indicated less corrosion on coated stents than uncoated controls. It was also noted that, from EIS data, the hydrophobic TMS plasma nanocoatings showed stable impedance modulus at 0.1 Hz after 21 day immersion in an electrolyte solution. These results suggest improved corrosion resistance of the 316L stainless steel stents by TMS plasma nanocoatings and great promise in reducing and blocking metallic ions releasing into the bloodstream. © 2014 Wiley Periodicals, Inc.

  9. Relaxation-systolic pressure relation. A load-independent assessment of left ventricular contractility

    NARCIS (Netherlands)

    Gillebert, T. C.; Leite-Moreira, A. F.; de Hert, S. G.

    1997-01-01

    This contribution reviews the regulation of left ventricular pressure (LVP) fall by load and relates this regulation to left ventricular contractility. Load regulation of LVP fall has to be distinguished from neurohumoral regulation, from effects induced by arterial reflected waves and from

  10. Renal artery denervation for treating resistant hypertension : definition of the disease, patient selection and description of the procedure.

    Science.gov (United States)

    Volpe, Massimo; Rosei, Enrico Agabiti; Ambrosioni, Ettore; Cottone, Santina; Cuspidi, Cesare; Borghi, Claudio; De Luca, Nicola; Fallo, Francesco; Ferri, Claudio; Mancia, Giuseppe; Morganti, Alberto; Muiesan, Maria Lorenza; Sarzani, Riccardo; Sechi, Leonardo; Tocci, Giuliano; Virdis, Agostino

    2012-12-01

    Arterial hypertension is responsible for a significant burden of cardiovascular morbidity and mortality, worldwide. Although several rational and integrated pharmacological strategies are available, the control of high blood pressure still remains largely unsatisfactory. Failure to achieve effective blood pressure control in treated hypertensive patients may have a substantial impact on individual global cardiovascular risk, since it significantly increases the risk of developing hypertension-related macrovascular and microvascular complications. Arterial hypertension is arbitrarily defined as 'resistant' or 'refractory' when the recommended blood pressure goals (clinic blood pressure below 140/90 mmHg or below 130/80 mmHg in patients with type 2 diabetes mellitus or nephropathy) are not achieved in the presence of a therapeutic strategy that includes lifestyle changes and at least three classes of antihypertensive drugs, including a diuretic, at adequate doses. Recently, an innovative non-pharmacological option has become available for treating resistant hypertension. Sympathetic denervation of renal arteries is a minimally invasive procedure that is performed via percutaneous access from the femoral artery. It consists of radiofrequency ablation of the afferent and efferent nerves of the renal sympathetic nervous system, with consequent isolation of renal parenchymal and juxtaglomerular structures from abnormal stimulation of the efferent adrenergic system. The present position paper of the Italian Society of Hypertension (SIIA) offers a diagnostic and therapeutic approach for the proper identification and effective clinical management of patients with resistant hypertension, who are candidates for renal artery denervation. These indications may have important implications not only from a clinical point of view, but also from an economic point of view, since a proper identification of patients with true resistant hypertension and an accurate selection of patients

  11. Hypercholesterolemia reduces collateral artery growth more dominantly than hyperglycemia or insulin resistance in mice

    NARCIS (Netherlands)

    Weel, V. van; Vries, M. de; Voshol, P.J.; Verloop, R.E.; Eilers, P.H.C.; Hinsbergh, V.W.M. van; Bockel, J.H. van; Quax, P.H.A.

    2006-01-01

    OBJECTIVE - Collateral artery development (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease, may be deregulated by vascular risk factors, eg, diabetes or hypercholesterolemia. Here, we compared the effects of either disturbed glucose metabolism or

  12. Reliability of contractile properties of the knee extensor muscles in individuals with post-polio syndrome.

    Directory of Open Access Journals (Sweden)

    Eric L Voorn

    Full Text Available To assess the reliability of contractile properties of the knee extensor muscles in 23 individuals with post-polio syndrome (PPS and 18 age-matched healthy individuals.Contractile properties of the knee extensors were assessed from repeated electrically evoked contractions on 2 separate days, with the use of a fixed dynamometer. Reliability was determined for fatigue resistance, rate of torque development (MRTD, and early and late relaxation time (RT50 and RT25, using the intraclass correlation coefficient (ICC and standard error of measurement (SEM, expressed as % of the mean.In both groups, reliability for fatigue resistance was good, with high ICCs (>0.90 and small SEM values (PPS: 7.1%, healthy individuals: 7.0%. Reliability for contractile speed indices varied, with the best values found for RT50 (ICCs>0.82, SEM values <2.8%. We found no systematic differences between test and retest occasions, except for RT50 in healthy subjects (p = 0.016.In PPS and healthy individuals, the reliability of fatigue resistance, as obtained from electrically evoked contractions is high. The reliability of contractile speed is only moderate, except for RT50 in PPS, demonstrating high reliability.This was the first study to examine the reliability of electrically evoked contractile properties in individuals with PPS. Our results demonstrate its potential to study mechanisms underlying muscle fatigue in PPS and to evaluate changes in contractile properties over time in response to interventions or from natural course.

  13. Reliability of contractile properties of the knee extensor muscles in individuals with post-polio syndrome.

    Science.gov (United States)

    Voorn, Eric L; Brehm, Merel A; Beelen, Anita; de Haan, Arnold; Nollet, Frans; Gerrits, Karin H L

    2014-01-01

    To assess the reliability of contractile properties of the knee extensor muscles in 23 individuals with post-polio syndrome (PPS) and 18 age-matched healthy individuals. Contractile properties of the knee extensors were assessed from repeated electrically evoked contractions on 2 separate days, with the use of a fixed dynamometer. Reliability was determined for fatigue resistance, rate of torque development (MRTD), and early and late relaxation time (RT50 and RT25), using the intraclass correlation coefficient (ICC) and standard error of measurement (SEM, expressed as % of the mean). In both groups, reliability for fatigue resistance was good, with high ICCs (>0.90) and small SEM values (PPS: 7.1%, healthy individuals: 7.0%). Reliability for contractile speed indices varied, with the best values found for RT50 (ICCs>0.82, SEM values <2.8%). We found no systematic differences between test and retest occasions, except for RT50 in healthy subjects (p = 0.016). In PPS and healthy individuals, the reliability of fatigue resistance, as obtained from electrically evoked contractions is high. The reliability of contractile speed is only moderate, except for RT50 in PPS, demonstrating high reliability. This was the first study to examine the reliability of electrically evoked contractile properties in individuals with PPS. Our results demonstrate its potential to study mechanisms underlying muscle fatigue in PPS and to evaluate changes in contractile properties over time in response to interventions or from natural course.

  14. Modulatory effects of taurine on jejunal contractility

    International Nuclear Information System (INIS)

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y.

    2014-01-01

    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca 2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism

  15. Modulatory effects of taurine on jejunal contractility

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y. [Dalian Medical University, Dalian, Liaoning (China)

    2014-10-14

    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca{sup 2+} dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

  16. Modulatory effects of taurine on jejunal contractility

    Directory of Open Access Journals (Sweden)

    Q.Y. Yao

    2014-12-01

    Full Text Available Taurine (2-aminoethanesulfonic acid is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

  17. Modulatory effects of taurine on jejunal contractility

    Science.gov (United States)

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y.

    2014-01-01

    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism. PMID:25387674

  18. Imaging and modeling of acute pressure-induced changes of collagen and elastin microarchitectures in pig and human resistance arteries.

    Science.gov (United States)

    Bloksgaard, Maria; Leurgans, Thomas M; Spronck, Bart; Heusinkveld, Maarten H G; Thorsted, Bjarne; Rosenstand, Kristoffer; Nissen, Inger; Hansen, Ulla M; Brewer, Jonathan R; Bagatolli, Luis A; Rasmussen, Lars M; Irmukhamedov, Akhmadjon; Reesink, Koen D; De Mey, Jo G R

    2017-07-01

    The impact of disease-related changes in the extracellular matrix (ECM) on the mechanical properties of human resistance arteries largely remains to be established. Resistance arteries from both pig and human parietal pericardium (PRA) display a different ECM microarchitecture compared with frequently used rodent mesenteric arteries. We hypothesized that the biaxial mechanics of PRA mirror pressure-induced changes in the ECM microarchitecture. This was tested using isolated pig PRA as a model system, integrating vital imaging, pressure myography, and mathematical modeling. Collagenase and elastase digestions were applied to evaluate the load-bearing roles of collagen and elastin, respectively. The incremental elastic modulus linearly related to the straightness of adventitial collagen fibers circumferentially and longitudinally (both R 2 ≥ 0.99), whereas there was a nonlinear relationship to the internal elastic lamina elastin fiber branching angles. Mathematical modeling suggested a collagen recruitment strain (means ± SE) of 1.1 ± 0.2 circumferentially and 0.20 ± 0.01 longitudinally, corresponding to a pressure of ~40 mmHg, a finding supported by the vital imaging. The integrated method was tested on human PRA to confirm its validity. These showed limited circumferential distensibility and elongation and a collagen recruitment strain of 0.8 ± 0.1 circumferentially and 0.06 ± 0.02 longitudinally, reached at a distending pressure below 20 mmHg. This was confirmed by vital imaging showing negligible microarchitectural changes of elastin and collagen upon pressurization. In conclusion, we show here, for the first time in resistance arteries, a quantitative relationship between pressure-induced changes in the extracellular matrix and the arterial wall mechanics. The strength of the integrated methods invites for future detailed studies of microvascular pathologies. NEW & NOTEWORTHY This is the first study to quantitatively relate pressure

  19. Effects of deoxycholylglycine, a conjugated secondary bile acid, on myogenic tone and agonist-induced contraction in rat resistance arteries.

    Directory of Open Access Journals (Sweden)

    Sandeep Khurana

    Full Text Available Bile acids (BAs regulate cardiovascular function via diverse mechanisms. Although in both health and disease serum glycine-conjugated BAs are more abundant than taurine-conjugated BAs, their effects on myogenic tone (MT, a key determinant of systemic vascular resistance (SVR, have not been examined.Fourth-order mesenteric arteries (170-250 µm isolated from Sprague-Dawley rats were pressurized at 70 mmHg and allowed to develop spontaneous constriction, i.e., MT. Deoxycholylglycine (DCG; 0.1-100 µM, a glycine-conjugated major secondary BA, induced reversible, concentration-dependent reduction of MT that was similar in endothelium-intact and -denuded arteries. DCG reduced the myogenic response to stepwise increase in pressure (20 to 100 mmHg. Neither atropine nor the combination of L-NAME (a NOS inhibitor plus indomethacin altered DCG-mediated reduction of MT. K(+ channel blockade with glibenclamide (K(ATP, 4-aminopyradine (K(V, BaCl(2 (K(IR or tetraethylammonium (TEA, K(Ca were also ineffective. In Fluo-2-loaded arteries, DCG markedly reduced vascular smooth muscle cell (VSM Ca(2+ fluorescence (∼50%. In arteries incubated with DCG, physiological salt solution (PSS with high Ca(2+ (4 mM restored myogenic response. DCG reduced vascular tone and VSM cytoplasmic Ca(2+ responses (∼50% of phenylephrine (PE- and Ang II-treated arteries, but did not affect KCl-induced vasoconstriction.In rat mesenteric resistance arteries DCG reduces pressure- and agonist-induced vasoconstriction and VSM cytoplasmic Ca(2+ responses, independent of muscarinic receptor, NO or K(+ channel activation. We conclude that BAs alter vasomotor responses, an effect favoring reduced SVR. These findings are likely pertinent to vascular dysfunction in cirrhosis and other conditions associated with elevated serum BAs.

  20. Measurement of pulmonary vascular resistance of Fontan candidates with pulmonary arterial distortion by means of pulmonary perfusion imaging

    International Nuclear Information System (INIS)

    Park, In-Sam; Mizukami, Ayumi; Tomimatsu, Hirofumi; Kondou, Chisato; Nakanishi, Toshio; Nakazawa, Makoto; Momma, Kazuo

    1998-01-01

    We measured the distribution of blood flow to the right (R) and left lung (L) by means of pulmonary perfusion imaging and calculated pulmonary vascular resistance (Rp) in 13 patients, whose right and left pulmonary artery pressures were different by 2 to 9 mmHg due to pulmonary arterial distortion (5 interruption, 8 stenosis). The right lung/left lung blood flow ratio was determined and from the ratio and the total pulmonary blood flow, which was determined using the Fick's principle, the absolute values of right and left pulmonary blood flow were calculated. Using the right and left pulmonary blood flow and the right and left pulmonary arterial pressures, right and left pulmonary vascular resistance were calculated, separately. Vascular resistance of the whole lung (Rp) was then calculated using the following equation. 1/(Rp of total lung)=1/(Rp of right lung)+1/(Rp of left lung). Rp calculated from this equation was 1.8+/-0.8 U·m 2 and all values were less than 3 U·m 2 (range 0.3-2.8). Rp estimated from the conventional method using the total pulmonary blood flow and pulmonary arterial pressures, without using the right/left blood flow ratio, ranging from 0.4 to 3.8 U·m 2 and 5 of 13 patients showed Rp>3 U·m 2 . All patients underwent Fontan operation successfully. These data indicated that this method is useful to estimate Rp and to determine the indication of Fontan operation in patients with pulmonary arterial distortions. (author)

  1. Krüppel-like Factor 5 contributes to pulmonary artery smooth muscle proliferation and resistance to apoptosis in human pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Paulin Roxane

    2011-09-01

    Full Text Available Background Pulmonary arterial hypertension (PAH is a vascular remodeling disease characterized by enhanced proliferation of pulmonary artery smooth muscle cell (PASMC and suppressed apoptosis. This phenotype has been associated with the upregulation of the oncoprotein survivin promoting mitochondrial membrane potential hyperpolarization (decreasing apoptosis and the upregulation of growth factor and cytokines like PDGF, IL-6 and vasoactive agent like endothelin-1 (ET-1 promoting PASMC proliferation. Krüppel-like factor 5 (KLF5, is a zinc-finger-type transcription factor implicated in the regulation of cell differentiation, proliferation, migration and apoptosis. Recent studies have demonstrated the implication of KLF5 in tissue remodeling in cardiovascular diseases, such as atherosclerosis, restenosis, and cardiac hypertrophy. Nonetheless, the implication of KLF5 in pulmonary arterial hypertension (PAH remains unknown. We hypothesized that KLF5 up-regulation in PAH triggers PASMC proliferation and resistance to apoptosis. Methods and results We showed that KFL5 is upregulated in both human lung biopsies and cultured human PASMC isolated from distal pulmonary arteries from PAH patients compared to controls. Using stimulation experiments, we demonstrated that PDGF, ET-1 and IL-6 trigger KLF-5 activation in control PASMC to a level similar to the one seen in PAH-PASMC. Inhibition of the STAT3 pathway abrogates KLF5 activation in PAH-PASMC. Once activated, KLF5 promotes cyclin B1 upregulation and promotes PASMC proliferation and triggers survivin expression hyperpolarizing mitochondria membrane potential decreasing PASMC ability to undergo apoptosis. Conclusion We demonstrated for the first time that KLF5 is activated in human PAH and implicated in the pro-proliferative and anti-apoptotic phenotype that characterize PAH-PASMC. We believe that our findings will open new avenues of investigation on the role of KLF5 in PAH and might lead to the

  2. Acute Ethanol Intake Induces NAD(P)H Oxidase Activation and Rhoa Translocation in Resistance Arteries.

    Science.gov (United States)

    Simplicio, Janaina A; Hipólito, Ulisses Vilela; Vale, Gabriel Tavares do; Callera, Glaucia Elena; Pereira, Camila André; Touyz, Rhian M; Tostes, Rita de Cássia; Tirapelli, Carlos R

    2016-11-01

    The mechanism underlying the vascular dysfunction induced by ethanol is not totally understood. Identification of biochemical/molecular mechanisms that could explain such effects is warranted. To investigate whether acute ethanol intake activates the vascular RhoA/Rho kinase pathway in resistance arteries and the role of NAD(P)H oxidase-derived reactive oxygen species (ROS) on such response. We also evaluated the requirement of p47phox translocation for ethanol-induced NAD(P)H oxidase activation. Male Wistar rats were orally treated with ethanol (1g/kg, p.o. gavage) or water (control). Some rats were treated with vitamin C (250 mg/kg, p.o. gavage, 5 days) before administration of water or ethanol. The mesenteric arterial bed (MAB) was collected 30 min after ethanol administration. Vitamin C prevented ethanol-induced increase in superoxide anion (O2-) generation and lipoperoxidation in the MAB. Catalase and superoxide dismutase activities and the reduced glutathione, nitrate and hydrogen peroxide (H2O2) levels were not affected by ethanol. Vitamin C and 4-methylpyrazole prevented the increase on O2- generation induced by ethanol in cultured MAB vascular smooth muscle cells. Ethanol had no effect on phosphorylation levels of protein kinase B (Akt) and eNOS (Ser1177 or Thr495 residues) or MAB vascular reactivity. Vitamin C prevented ethanol-induced increase in the membrane: cytosol fraction ratio of p47phox and RhoA expression in the rat MAB. Acute ethanol intake induces activation of the RhoA/Rho kinase pathway by a mechanism that involves ROS generation. In resistance arteries, ethanol activates NAD(P)H oxidase by inducing p47phox translocation by a redox-sensitive mechanism. O mecanismo da disfunção vascular induzido pelo consumo de etanol não é totalmente compreendido. Justifica-se, assim a identificação de mecanismos bioquímicos e moleculares que poderiam explicar tais efeitos. Investigar se a ingestão aguda de etanol ativa a via vascular RhoA/Rho quinase

  3. Biliary Cast Syndrome: Hepatic Artery Resistance Index, Pathological Changes, Morphology and Endoscopic Therapy

    Directory of Open Access Journals (Sweden)

    Hu Tian

    2015-01-01

    Full Text Available Background: Biliary cast syndrome (BCS was a postoperative complication of orthotopic liver transplantation (OLT, and the reason for BSC was considered to relate with ischemic type biliary lesions. This study aimed to evaluate the relationship between BCS following OLT and the hepatic artery resistance index (HARI, and to observe pathological changes and morphology of biliary casts. Methods: Totally, 18 patients were diagnosed with BCS by cholangiography following OLT using choledochoscope or endoscopic retrograde cholangiopancreatography. In addition, 36 patients who did not present with BCS in the corresponding period had detectable postoperative HARI on weeks 1, 2, 3 shown by color Doppler flow imaging. The compositions of biliary casts were analyzed by pathological examination and scanning electron microscopy. Results: HARI values of the BCS group were significantly decreased as compared with the non-BCS group on postoperative weeks 2 and 3 (P 1 (OR = 1.300; 1.223; and 1.889, respectively. The OR of HARI 3 was statistically significant (OR = 1.889; 95% confidence interval = 1.166-7.490; P = 0.024. The compositions of biliary casts were different when bile duct stones were present. Furthermore, vascular epithelial cells were found by pathological examination in biliary casts. Conclusions: HARI may possibly serve as an independent risk factor and early predictive factor of BCS. Components and formation of biliary casts and bile duct stones are different.

  4. Effects of thrombin, PAR-1 activating peptide and a PAR-1 antagonist on umbilical artery resistance in vitro

    Directory of Open Access Journals (Sweden)

    Elliott John T

    2005-02-01

    Full Text Available Abstract Background The non-thrombotic effects of thrombin in cardiovascular tissues, as mediated via the protease activated receptors (PARs, and particularly PAR-1, have been the focus of much recent research. The aims of this study were to evaluate the effects of thrombin, a specific PAR-1 activating peptide (PAR1-AP, and a PAR-1 antagonist on human umbilical artery tone in vitro. Methods Human umbilical artery samples were obtained from 17 women at term. Arterial rings were suspended under physiologic conditions for isometric recording. The in vitro effects of thrombin (0.5 units/mL to 3 units/mL, PAR1-AP TFLLR-NH2 [10(-9 to 10(-6 M], and PAR-1 antagonist (N-trans cinnamoyl- p-fluoroPhe-p-guanidinoPhe-Leu-Arg-Orn-NH2 [10(-9 M to 10(-5 M] on umbilical artery tone were measured. Results Both thrombin and TFLLR-NH2 exerted a potent cumulative vasodilatory effect on human umbilical artery resistance (P 0.05. Conclusion These findings highlight a potential role for thrombin and PAR-1 receptors in vascular regulation of feto-placental blood flow in normal pregnancy, and in association with the vascular lesions associated with IUGR and pre-eclampsia.

  5. Assessing Collagen and Elastin Pressure-dependent Microarchitectures in Live, Human Resistance Arteries by Label-free Fluorescence Microscopy

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Thorsted, Bjarne; Brewer, Jonathan R

    2018-01-01

    The pathogenic contribution of resistance artery remodeling is documented in essential hypertension, diabetes and the metabolic syndrome. Investigations and development of microstructurally motivated mathematical models for understanding the mechanical properties of human resistance arteries...... in health and disease have the potential to aid understanding how disease and medical treatments affect the human microcirculation. To develop these mathematical models, it is essential to decipher the relationship between the mechanical and microarchitectural properties of the microvascular wall...... of interest. Image analyses are described for quantifying i) pressure-induced changes in internal elastic lamina branching angles and adventitial collagen straightness using Fiji and ii) collagen and elastin volume densities determined using Ilastik software. Preferably all mechanical and imaging measurements...

  6. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    Science.gov (United States)

    Ianuzzo, C. D.; Chen, V.

    1977-01-01

    Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

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

    International Nuclear Information System (INIS)

    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

    2015-01-01

    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 N 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

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

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    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.

  9. Arterial bicarbonate may be a useful indicator of inadequate cortisol response in children with catecholamine resistant septic shock

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    M B Maralihalli

    2013-01-01

    Full Text Available Objective: To study the clinical and biochemical parameters that can predict cortisol insufficiency in children with septic shock. Design: prospective, observational study. Setting: tertiary health-care center. Patients/Subjects: Fifty children admitted with the catecholamine resistant septic shock to a tertiary health-care center. Materials and Methods: At the time of hospitalization all patients underwent detailed clinical evaluation including, history and physical examination, evaluation with the complete blood count, serum cortisol, renal function tests, liver function tests, prothrombin time activated partial thromboplastin time, arterial blood gas analysis, urine analysis, chest roentgenogram, ultrasonography of the abdomen and chest, urine, and blood culture for bacteria and fungi. Results: Out of 50 children with the catecholamine resistant septic shock, seven had adrenal insufficiency (serum cortisol <18 μg/dl. Of all parameters studied, only arterial bicarbonate at the time of admission to intensive care predicted adrenal insufficiency. On Receptor operative characteristic curve analysis, a bicarbonate level of 10.9 mEq/L had the best accuracy to predict adrenal insufficiency. Conclusion: Arterial bicarbonate may be used as a rapid test for provisional identification of adrenal insufficiency among children with the catecholamine resistant septic shock.

  10. Perinatal development influences mechanisms of bradykinin-induced relaxations in pulmonary resistance and conduit arteries differently.

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    Boels, P J; Deutsch, J; Gao, B; Haworth, S G

    2001-07-01

    As bradykinin (BYK) relaxes conduit (EPA) and resistance (RPA) pulmonary arteries from both perinatal and adult lungs, we investigated whether this vasodilator's relaxation-mechanisms were altered during perinatal development, differed between EPA and RPA and differed with other endothelium-dependent vasodilators, acetyicholine (ACH) and substance P (SP). Arteries from mature foetal (5 days), neonatal (approximately 5 min), newborn (60-84 h) and adult pigs (> or =6 months) were isolated, mounted for in vitro isometric force recording, activated with PGF(2alpha) (30 micromol/l) and relaxed with BYK (10 pmol/l-1 micromol/l), SP (10 pmol/l-0.1 micromol/l) or ACH (1 nmol/l-1 mmol/l). (i) BYK: L-NAME (100 micromol/l) attenuated relaxations in foetal EPA ( approximately 55%) but nearly abolished them in the adult ( approximately 80%). In RPA, L-NAME nearly abolished ( approximately 90%) relaxations in the foetus and this effect diminished progressively with age to approximately 20% in the adult. Indomethacin (IND, micromol/l) attenuated relaxations in neonatal (approximately 25%), new-born and adult EPA (both approximately 45%). Together, L-NAME and IND abolished relaxations in all EPA and in neonatal RPA but not in older RPA. SKF525a (100 micromol/l) attenuated relaxations in foetal RPA ( approximately 4%), diminishing in the adult RPA to approximately 10%. Together, SKF52Sa and L-NAME largely abolished relaxations in postnatal RPA (approximately 80%). Activation with K(+)=125 mmol/l attenuated relaxations in adult EPA (approximately 80%), foetal RPA ( approximately 45%) and neonatal RPA (approximately 75%) and abolished relaxations in RPA from older ages. (ii) ACH: L-NAME abolished relaxations in new-born EPA and RPA. In adult EPA, combined L-NAME and IND moderately attenuated relaxations. (iii) SP: Combined application of L-NAME and IND attenuated relaxations to a similar degree in new-born and adult EPA and RPA. In postnatal EPA, BYK-relaxations depend completely on

  11. The relationship of pulmonary vascular resistance and compliance to pulmonary artery wedge pressure during submaximal exercise in healthy older adults.

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    Wright, Stephen P; Granton, John T; Esfandiari, Sam; Goodman, Jack M; Mak, Susanna

    2016-06-15

    A consistent inverse hyperbolic relationship has been observed between pulmonary vascular resistance and compliance, although changes in pulmonary artery wedge pressure (PAWP) may modify this relationship. This relationship predicts that pulmonary artery systolic, diastolic and mean pressure maintain a consistent relationship relative to the PAWP. We show that, in healthy exercising human adults, both pulmonary vascular resistance and compliance decrease in relation to exercise-associated increases in PAWP. Pulmonary artery systolic, diastolic and mean pressures maintain a consistent relationship with one another, increasing linearly with increasing PAWP. Increases in PAWP in the setting of exercise are directly related to a decrease in pulmonary vascular compliance, despite small decreases in pulmonary vascular resistance, thereby increasing the pulsatile afterload to the right ventricle. The resistive and pulsatile components of right ventricular afterload (pulmonary vascular resistance, Rp; compliance, Cp) are related by an inverse hyperbolic function, expressed as their product known as RpCp-time. The RpCp-time exhibits a narrow range, although it may be altered by the pulmonary artery wedge pressure (PAWP). Identifying the determinants of RpCp-time should improve our understanding of the physiological behaviour of pulmonary arterial systolic (PASP), diastolic (PADP) and mean (mPAP) pressures in response to perturbations. We examined the effect of exercise in 28 healthy non-athletic adults (55 ± 6 years) who underwent right heart catheterization to assess haemodynamics and calculate Rp and Cp. Measurements were made at rest and during two consecutive 8-10 min stages of cycle ergometry, at targeted heart-rates of 100 beats min(-1) (Light) and 120 beats min(-1) (Moderate). Cardiac output increased progressively during exercise. PASP, PADP, mPAP and PAWP increased for Light exercise, without any further rise for Moderate exercise. RpCp-time decreased for

  12. Cigarette smoke extracts promote vascular smooth muscle cell proliferation and enhances contractile responses in the vasculature and airway.

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    Xu, Cang-Bao; Lei, Ying; Chen, Qingwen; Pehrson, Christina; Larsson, Lennart; Edvinsson, Lars

    2010-12-01

    Cigarette smoke exposure is a strong risk factor for cardiovascular and respiratory diseases. However, the knowledge about how cigarette smoke induces damage to vasculature and airway is limited. The present study was designed to examine the effects of cigarette smoke particles extracted by heptane (heptane-soluble smoke particles, HSP), by water (water-soluble smoke particles, WSP) and by DMSO (DMSO-soluble smoke particles, DSP), which represent lipophilic, hydrophilic and ambiphoteric constituents from the cigarette smoke, respectively. Human aortic smooth muscle cell (HASMC) proliferation was assessed in cell culture. Rat resistance artery and airway contractile responses to serotonin, U46619, phenylephrine, noradrenaline, acetylcholine, des-Arg⁹-bradykinin, bradykinin, sarafotoxin 6c and endothelin-1 were monitored by a sensitive myograph system. Immunocytochemistry and cell-based phosphoELISA assay were used to demonstrate activation of extracellular signal-regulated kinases 1/2 (ERK1/2). For the first time, our results demonstrate that although all the three extracts promote HASMC proliferation, the HSP and DSP effects occur earlier. HSP and DSP, but not WSP, increase the contractile responses to sarafotoxin 6c, U46619 or bradykinin in rat mesenteric artery and/or in bronchi. ERK1/2 is activated by HSP and DSP in HASMCs and inhibition of ERK1/2 abrogated the smoke extracts-induced HASMC proliferation, while blockage of nicotinic receptors had no effects, suggesting that the toxic effects of the smoke extracts occur via activation of intracellular ERK1/2 signalling, but not nicotinic receptors. © 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.

  13. Cellular contractility requires ubiquitin mediated proteolysis.

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    Yuval Cinnamon

    Full Text Available BACKGROUND: Cellular contractility, essential for cell movement and proliferation, is regulated by microtubules, RhoA and actomyosin. The RhoA dependent kinase ROCK ensures the phosphorylation of the regulatory Myosin II Light Chain (MLC Ser19, thereby activating actomyosin contractions. Microtubules are upstream inhibitors of contractility and their depolymerization or depletion cause cells to contract by activating RhoA. How microtubule dynamics regulates RhoA remains, a major missing link in understanding contractility. PRINCIPAL FINDINGS: We observed that contractility is inhibited by microtubules not only, as previously reported, in adherent cells, but also in non-adhering interphase and mitotic cells. Strikingly we observed that contractility requires ubiquitin mediated proteolysis by a Cullin-RING ubiquitin ligase. Inhibition of proteolysis, ubiquitination and neddylation all led to complete cessation of contractility and considerably reduced MLC Ser19 phosphorylation. CONCLUSIONS: Our results imply that cells express a contractility inhibitor that is degraded by ubiquitin mediated proteolysis, either constitutively or in response to microtubule depolymerization. This degradation seems to depend on a Cullin-RING ubiquitin ligase and is required for cellular contractions.

  14. Low mercury concentrations cause oxidative stress and endothelial dysfunction in conductance and resistance arteries.

    Science.gov (United States)

    Wiggers, G A; Peçanha, F M; Briones, A M; Pérez-Girón, J V; Miguel, M; Vassallo, D V; Cachofeiro, V; Alonso, M J; Salaices, M

    2008-09-01

    Increased cardiovascular risk after mercury exposure has been described, but the underlying mechanisms are not well explored. We analyzed the effects of chronic exposure to low mercury concentrations on endothelium-dependent responses in aorta and mesenteric resistance arteries (MRA). Wistar rats were treated with mercury chloride (1st dose 4.6 microg/kg, subsequent dose 0.07 microg.kg(-1).day(-1) im, 30 days) or vehicle. Blood levels at the end of treatment were 7.97 +/- 0.59 ng/ml. Mercury treatment: 1) did not affect systolic blood pressure; 2) increased phenylephrine-induced vasoconstriction; 3) reduced acetylcholine-induced vasodilatation; and 4) reduced in aorta and abolished in MRA the increased phenylephrine responses induced by either endothelium removal or the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME, 100 microM). Superoxide dismutase (SOD, 150 U/ml) and the NADPH oxidase inhibitor apocynin (0.3 mM) decreased the phenylephrine-induced contraction in aorta more in mercury-treated rats than controls. In MRA, SOD did not affect phenylephrine responses; however, when coincubated with l-NAME, the l-NAME effect on phenylephrine response was restored in mercury-treated rats. Both apocynin and SOD restored the impaired acetylcholine-induced vasodilatation in vessels from treated rats. Endothelial NOS expression did not change in aorta but was increased in MRA from mercury-treated rats. Vascular O2(-) production, plasmatic malondialdehyde levels, and total antioxidant status increased with the mercury treatment. In conclusion, chronic exposure to low concentrations of mercury promotes endothelial dysfunction as a result of the decreased NO bioavailability induced by increases in oxidative stress. These findings offer further evidence that mercury, even at low concentrations, is an environmental risk factor for cardiovascular disease.

  15. Resistive index of prostate capsular arteries: a newly identified parameter to diagnose and assess bladder outlet obstruction in patients with benign prostatic hyperplasia.

    Science.gov (United States)

    Zhang, Xuefeng; Li, Gang; Wei, Xuedong; Mo, Xiaodong; Hu, Linkun; Zha, Yueqin; Hou, Jianquan

    2012-09-01

    We evaluated the association of the resistive index of the prostate capsular arteries and bladder outlet obstruction severity in men with benign prostatic hyperplasia. A total of 74 patients histologically diagnosed with benign prostatic hyperplasia were ultimately enrolled in this prospective study. Urodynamics were performed by a urologist to determine bladder outlet obstruction. Baseline parameters measured in patients with benign prostatic hyperplasia were the prostate capsular artery resistive index, International Prostate Symptom Score, quality of life score, total prostate and transition zone volume, and the transition zone index. ROC curves were produced to calculate the ROC AUC and evaluate the diagnostic performance of the prostate capsular artery resistive index, International Prostate Symptom Score, obstructive symptoms, total prostate and transition zone volume, and the transition zone index for bladder outlet obstruction. Significant difference between patients with and without bladder outlet obstruction was observed in the resistive index, which showed the highest coefficient with the degree of obstruction (r = 0.712, p prostate capsular artery resistive index had the maximum AUC of 0.823. The prostate capsular artery resistive index is significantly higher in patients with benign prostatic hyperplasia related bladder outlet obstruction than in those without such obstruction. The resistive index might serve as a novel indicator to diagnose and assess bladder outlet obstruction in patients with benign prostatic hyperplasia. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  16. Insulin resistance is associated with lower arterial blood flow and reduced cortical perfusion in cognitively asymptomatic middle-aged adults.

    Science.gov (United States)

    Hoscheidt, Siobhan M; Kellawan, J Mikhail; Berman, Sara E; Rivera-Rivera, Leonardo A; Krause, Rachel A; Oh, Jennifer M; Beeri, Michal S; Rowley, Howard A; Wieben, Oliver; Carlsson, Cynthia M; Asthana, Sanjay; Johnson, Sterling C; Schrage, William G; Bendlin, Barbara B

    2017-06-01

    Insulin resistance (IR) is associated with poor cerebrovascular health and increased risk for dementia. Little is known about the unique effect of IR on both micro- and macrovascular flow particularly in midlife when interventions against dementia may be most effective. We examined the effect of IR as indexed by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) on cerebral blood flow in macro- and microvessels utilizing magnetic resonance imaging (MRI) among cognitively asymptomatic middle-aged individuals. We hypothesized that higher HOMA-IR would be associated with reduced flow in macrovessels and lower cortical perfusion. One hundred and twenty cognitively asymptomatic middle-aged adults (57 ± 5 yrs) underwent fasting blood draw, phase contrast-vastly undersampled isotropic projection reconstruction (PC VIPR) MRI, and arterial spin labeling (ASL) perfusion. Higher HOMA-IR was associated with lower arterial blood flow, particularly within the internal carotid arteries (ICAs), and lower cerebral perfusion in several brain regions including frontal and temporal lobe regions. Higher blood flow in bilateral ICAs predicted greater cortical perfusion in individuals with lower HOMA-IR, a relationship not observed among those with higher HOMA-IR. Findings provide novel evidence for an uncoupling of macrovascular blood flow and microvascular perfusion among individuals with higher IR in midlife.

  17. Differential effect of amylin on endothelial-dependent vasodilation in mesenteric arteries from control and insulin resistant rats.

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    Mariam El Assar

    Full Text Available Insulin resistance (IR is frequently associated with endothelial dysfunction and has been proposed to play a major role in cardiovascular disease (CVD. On the other hand, amylin has long been related to IR. However the role of amylin in the vascular dysfunction associated to IR is not well addressed. Therefore, the aim of the study was to assess the effect of acute treatment with amylin on endothelium-dependent vasodilation of isolated mesenteric arteries from control (CR and insulin resistant (IRR rats and to evaluate the possible mechanisms involved. Five week-old male Wistar rats received 20% D-fructose dissolved in drinking water for 8 weeks and were compared with age-matched CR. Plasmatic levels of glucose, insulin and amylin were measured. Mesenteric microvessels were dissected and mounted in wire myographs to evaluate endothelium-dependent vasodilation to acetylcholine. IRR displayed a significant increase in plasmatic levels of glucose, insulin and amylin and reduced endothelium-dependent relaxation when compared to CR. Acute treatment of mesenteric arteries with r-amylin (40 pM deteriorated endothelium-dependent responses in CR. Amylin-induced reduction of endothelial responses was unaffected by the H2O2 scavenger, catalase, but was prevented by the extracellular superoxide scavenger, superoxide dismutase (SOD or the NADPH oxidase inhibitor (VAS2870. By opposite, amylin failed to further inhibit the impaired relaxation in mesenteric arteries of IRR. SOD, or VAS2870, but not catalase, ameliorated the impairment of endothelium-dependent relaxation in IRR. At concentrations present in insulin resistance conditions, amylin impairs endothelium-dependent vasodilation in mircrovessels from rats with preserved vascular function and low levels of endogenous amylin. In IRR with established endothelial dysfunction and elevated levels of amylin, additional exposure to this peptide has no effect on endothelial vasodilation. Increased superoxide

  18. Invasive assessment of renal artery atherosclerotic disease and resistant hypertension before renal sympathetic denervation.

    Science.gov (United States)

    Ribichini, Flavio; Pighi, Michele; Zivelonghi, Carlo; Gambaro, Alessia; Valvo, Enrico; Lupo, Antonio; Vassanelli, Corrado

    2013-01-01

    Renal sympathetic denervation (RSD) is emerging as a new therapeutic option for patients with severe hypertension refractory to medical therapy. The presence of a renal artery stenosis may be both a cause of secondary hypertension and a contraindication to RSD if a renal artery stent is implanted; therefore, the definition of the functional importance of a renal artery stenosis in a patient with refractory hypertension is crucial. We describe the imaging and functional intravascular assessment of an angiographically severe stenosis of the renal artery in a patient with severe refractory hypertension, by means of intravascular ultrasound (IVUS), and measurement of the translesional pressure gradient with a pressure wire. Pressure wire examination excluded any severity of the stenosis, and IVUS showed the presence of a dissected plaque that resolved spontaneously after 3 months of intensive medical therapy and high-dose statin. Subsequently the patient was treated with RSD, achieving a significant effect on blood pressure control. Intravascular imaging and functional assessment of renal artery anatomy in patients with atherosclerotic disease may prove particularly suited to patients with refractory hypertension and multilevel vascular disease who are considered for endovascular therapies, either renal artery stenting or RSD.

  19. HAEMODYNAMIC RESPONSE DURING EXERCISE TESTING IN PATIENTS WITH CORONARY ARTERY DISEASE UNDERGOING A CARDIAC REHABILITATION PROGRAMME

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    J. Siebert

    2011-09-01

    Full Text Available Haemodynamic monitoring during exercise testing is seldom used during cardiac rehabilitation. The aim was to evaluate haemodynamic changes using the cardiac impedance method during exercise testing in patients after percutaneous coronary interventions and coronary artery bypass grafting during cardiac rehabilitation. Thirty (25 M; 5 F patients were included in the programme. The group was divided according to ejection fraction (EF: low – below 50% normal – equal to or above 50%. The exercise test was performed simultaneously with a four-electrode impedance cardiogram before and after rehabilitation. ECG, blood pressure, thoracic impedance, first derivative dz/dt, stroke volume (SV and cardiac output were recorded. Contractility index (Heather index – HI and vascular peripheral resistance were calculated. The pattern of haemodynamic changes was normal in 24 patients. The deflection points for HI and SV trend patterns were observed among patients with low EF. The contractility index decreased 90 s before maximal exercise and after the next 30-60 s a deflection point was observed in SV curve trends. In 24 patients with normal EF the contractility index trends did not decrease and SV trends increased until the end of exercise or a deflection point was not noted. The deflection points of the contractility index and SV curves were observed before the clinical indications for exercise test termination appeared in patients with a low ejection fraction. Impedance cardiography may indicate the threshold of the workload during real-time exercise testing.

  20. Effects of regular physical activity on pain, anxiety, and depression in patients with treatment-resistant arterial hypertension

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    Piotr Jan Kruk

    2016-09-01

    Full Text Available Background . Medical experts and professional societies commonly recommend regular physical activity to patients with arterial hypertension. However there is little evidence of the influence of physical exercise on treatment-resistant arterial hypertension. Objectives. The aim of the study was to analyze the influence of physical activity, intensified with additional training support, and followed up with SMS reminders regarding pain, anxiety, and depression in patients with resistant hypertension. Material and methods. The study group consisted of 53 patients, including 27 who fulfilled the criteria for resistant hypertension, and a control group of 26 patients with well-controlled blood pressure. Initially, 24-hour monitoring of blood pressure, anthropometric measurements, and measurements of body composition by means of electric bioimpedance were conducted after the third and sixth month, and a mobile activity profile was defined by means of accelerometric measurements conducted for subsequent 72 hours. The patients completed the Hospital Anxiety and Depression Scale (HA DS and the Roland and Morris Disability Questionnaire (RMDQ. The patients were advised to perform regular aerobic physical activity in accordance with the guidelines of the American Heart Association. Results . After 6 months, the back pain score as assessed with RMDQ had reduced from 8.2 ± 7.5 to 6 ± 5.9 (p = 0.01 in subjects with treatment-resistant hypertension. Similar results applied to anxiety (score 8.2 ± 4 vs. 9.3 ± 4.4 at baseline; p = 0.02 and depression as measured with HA DS (5.3 ± 3 vs. 6.9 ± 3.7 at baseline; p = 0.01. There was a significant positive correlation between the changes in the pain score (RMDQ and the changes in the 24 h and nighttime systolic blood pressure, pulse pressure, and anxiety. Conclusions . Regular physical activity may have a beneficial effect on anxiety, depression, and pain in patients with treatmentresistant hypertension.

  1. Acoustic Radiation Force Impulse Imaging of the Transplant Kidney: Correlation Between Cortical Stiffness and Arterial Resistance in Early Post-transplant Period.

    Science.gov (United States)

    Wang, H-K; Lai, Y-C; Lin, Y-H; Chiou, H-J; Chou, Y-H

    2017-06-01

    Acoustic radiation force impulse (ARFI) imaging is a noninvasive imaging modality for quantitative assessment of tissue stiffness. This study utilized ARFI imaging to assess the stiffness of a transplant renal cortex within the first month after renal transplantation and to explore the correlation between the cortical stiffness and arterial resistance of the transplant kidney. Forty renal transplant recipients (male/female = 26/14; mean age: 45.3 years; deceased donor/living related donor = 27/13) were included in this study. ARFI imaging with virtual touch tissue imaging quantification was applied to assess the stiffness of the transplant renal cortex by using a linear ultrasound transducer. Arterial resistance was acquired by spectral Doppler examination of the main artery and intrarenal arteries of the transplant kidney using a curvilinear ultrasound transducer. The stiffness of transplant renal cortex was expressed as shear wave velocity (m/s). The mean value of cortical stiffness was 3.19 ± 1.01 m/s (range: 1.55-5.54). The stiffness of transplant renal cortex was positively correlated with the resistance index of the main renal artery (r = 0.55, P = .001), segmental artery (r = 0.43, P = .005), and interlobar artery (r = 0.42, P = .006). The stiffness of a transplant renal cortex is positively correlated with the arterial resistance of the renal transplant in the early post-transplant period. This result indicates that, in addition to renal fibrosis, the stiffness of the transplant renal cortex is also influenced by the hemodynamics of the transplant kidney. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Ultrasound-assessed perirenal fat is related to increased ophthalmic artery resistance index in HIV-1 patients.

    Science.gov (United States)

    Grima, Pierfrancesco; Guido, Marcello; Chiavaroli, Roberto; Zizza, Antonella

    2010-06-30

    The introduction of highly active antiretroviral therapy (HAART) has dramatically changed the prognosis of human immunodeficiency virus (HIV) infection, with a significant decline in morbidity and mortality.Changes in body fat distribution are a common finding in individuals with HIV infection being treated with antiretrovirals, and this condition (collectively termed lipodystrophy syndrome) is associated with depletion of subcutaneous fat, increased triglycerides and insulin resistance. Obesity, particularly visceral obesity, is associated with increased risk of cardiovascular disease. Therefore, estimating visceral fat distribution is important in identifying subjects at high risk for cardiovascular disease.The aim of our study was to evaluate whether perirenal fat thickness (PRFT), a parameter of central obesity, is related to ophthalmic artery resistance index (OARI), an index of occlusive carotid artery disease in HIV-1 infected patients. We enrolled 88 consecutive HIV-1-infected patients receiving highly active antiretroviral therapy for more than 12 months, in a prospective cohort study. Echographically measured PRFT and OARI, as well as serum metabolic parameters, were evaluated. PRFT and OARI were measured by 3.75 MHz convex and 7.5 MHz linear probe, respectively. The means of PRFT and OARI in HIV-1-infected patients with visceral obesity was considerably higher than in patients without it (p 0.74 (sensitivity 78.9%, specificity 82.8%). Our data indicate that ultrasound assessment of PRFT may have potential as a marker of increased endothelial damage with specific involvement of the ocular vascular region in HIV-1-infected patients.

  3. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes.

    Science.gov (United States)

    Chilton, R; Tikkanen, I; Cannon, C P; Crowe, S; Woerle, H J; Broedl, U C; Johansen, O E

    2015-12-01

    To determine the effects of empagliflozin on blood pressure (BP) and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes mellitus (T2DM). We conducted a post hoc analysis of data from a phase III trial in patients with T2DM and hypertension receiving 12 weeks' empagliflozin and four phase III trials in patients with T2DM receiving 24 weeks' empagliflozin (cohort 1, n = 823; cohort 2, n = 2477). BP was measured using 24-h BP monitoring (cohort 1) or seated office measurements (cohort 2). Empagliflozin reduced systolic BP (SBP) and diastolic BP in both cohorts (p Empagliflozin reduced pulse pressure (PP; adjusted mean difference vs placebo cohort 1: -2.3 mmHg; cohort 2: -2.3 mmHg), mean arterial pressure (MAP; cohort 1, -2.3 mmHg; cohort 2, -2.1 mmHg) and double product (cohort 1, -385 mmHg × bpm; cohort 2, -369 mmHg × bpm) all p empagliflozin in cohort 1 (p = 0.059 vs placebo). AASI was not measured in cohort 2. Subgroup analyses showed that there were greater reductions in PP with increasing baseline SBP in cohort 1 (p = 0.092). In cohort 2, greater reductions in MAP were achieved in patients with higher baseline SBP (p = 0.027) and greater reductions in PP were observed in older patients (p = 0.011). Empagliflozin reduced BP and had favourable effects on markers of arterial stiffness and vascular resistance. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  4. CLINICAL IMPORTANCE OF ENDOTHELIAL DYSFUNCTION AND INSULIN RESISTANCE SYNDROME IN PATIENTS WITH GOUT ASSOCIATED WITH ARTERIAL HYPERTENSION

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    N. N. Kushnarenko

    2015-09-01

    Full Text Available Aim. To study the endothelium status and determine the correlation between endothelial dysfunction and glucose metabolism in men with gout associated with arterial hypertension (HT.Material and methods. Patients (n=175, all are males with gout were enrolled into the study. Ambulatory blood pressure monitoring (ABPM was performed in all patients. Endothelial function was studied in tests with reactive hyperemia (endothelium-dependent reaction and nitroglycerin (endothelium independent reaction in brachial artery by ultrasonic Doppler examination. The level of nitrite-nitrate and endothelin-1 in blood serum was determined by ELISA technique. Fasting blood glucose and oral glucose tolerance tests were performed as well as fasting insulin blood level was determined by immunoenzyme method. Insulin-resistance index (HOMA-IR was calculated. Patients with HOMA- IR>2.77 were considered as insulin-resistant.Results. Patients with gout demonstrated endothelial deterioration associated with activation of nitroxid producing function, elevation in endothelin-1 serum level (1.36 fmol/ml [0.91; 2.32 fmol/ml] vs 0.19 fmol/ml [0.16; 0.27 fmol/ml] in controls, p<0.05 and impairments of endothelium-dependent vasodilation (6.4% [3.3; 7.3%] vs 17.8% [12.7; 23.9%] in controls, p<0.05. The revealed changes were the most marked in patients with gout associated with HT. The correlation between some endothelial dysfunction in- dices and glucose metabolism was observed.Conclusion. ABPM, brachial artery endothelium-dependent vasodilation and glucose metabolism status should be studied in patients with gout. Complex treatment of cardiovascular diseases in patients with gout should include ω-3 polyunsaturated fatty acids, angiotensin receptor antagonists should be used for antihypertensive therapy.

  5. Sex differences in associations between insulin resistance, heart rate variability, and arterial stiffness in healthy women and men: a physiology study.

    Science.gov (United States)

    Rannelli, Luke Anthony; MacRae, Jennifer M; Mann, Michelle C; Ramesh, Sharanya; Hemmelgarn, Brenda R; Rabi, Doreen; Sola, Darlene Y; Ahmed, Sofia B

    2017-04-01

    Diabetes confers greater cardiovascular risk to women than to men. Whether insulin-resistance-mediated risk extends to the healthy population is unknown. Measures of insulin resistance (fasting insulin, homeostatic model assessment, hemoglobin A1c, quantitative insulin sensitivity check index, glucose) were determined in 48 (56% female) healthy subjects. Heart rate variability (HRV) was calculated by spectral power analysis and arterial stiffness was determined using noninvasive applanation tonometry. Both were measured at baseline and in response to angiotensin II infusion. In women, there was a non-statistically significant trend towards increasing insulin resistance being associated with an overall unfavourable HRV response and increased arterial stiffness to the stressor, while men demonstrated the opposite response. Significant differences in the associations between insulin resistance and cardiovascular physiological profile exist between healthy women and men. Further studies investigating the sex differences in the pathophysiology of insulin resistance in cardiovascular disease are warranted.

  6. Use of Heart Rate Variability to Estimate Lactate Threshold in Coronary Artery Disease Patients during Resistance Exercise.

    Science.gov (United States)

    Simões, Rodrigo P; Mendes, Renata G; Castello-Simões, Viviane; Catai, Aparecida M; Arena, Ross; Borghi-Silva, Audrey

    2016-12-01

    The aim of this study was to investigate whether it is possible to identify the first turn point of blood lactate (BL) concentration (1 st lactate threshold - LT1) during a discontinuous resistance exercise protocol in coronary artery disease (CAD) patients and verify if heart rate variability (HRV) responses are consistent with BL responses. A total of 22 elderly men, 12 with CAD and 10 apparently healthy (control group = CG), underwent one-repetition maximum (1RM) testing on an inclined leg press. Discontinuous resistance exercise testing (DRET) was initiated at 10% of the 1RM with subsequent increases of 10% until 30% and after this percentage, 5% increments of 1RM was carried out. The load corresponding to LT1 was approximately 30% 1RM in both groups; and the LT1 estimate by HRV was associated with BL responses. HRV indices representing parasympathetic modulation decreased with increasing loads until LT1 and stabilized thereafter in both groups, and HRV indices representing sympathetic and parasympathetic modulations only increased in the CAD group from 30% 1RM with higher values after this load in relation to the CG. We conclude HRV appears to be an effective tool to estimate the LT1 during discontinuous resistance exercise in patients with CAD. In addition, these results may have an impact on the prescription of endurance resistance exercise in the CAD population, as cardiac vagal modulation is an important indicator of cardiovascular protection and the over-activity of sympathetic modulation is related to cardiovascular risk.

  7. Anti-peroxynitrite treatment ameliorated vasorelaxation of resistance arteries in aging rats: involvement with NO-sGC-cGKs pathway.

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    Lu Ma

    Full Text Available Declined vasorelaxation function in aging resistance arteries is responsible for aging-related multiple organ dysfunctions. The aim of the present study is to explore the role of peroxynitrite (ONOO- in aging resistance arterial vasorelaxation dysfunction and the possible mechanism. In the present study, young (3-4 months olds and aging (20 months olds male SD rats were randomized to receive vehicle (Saline or FeTMPyP (ONOO- scavenger for 2 weeks. The vasorelaxation of resistance arteries was determined in vitro; NOx level was tested by a colorimetric assay; the expression of nitrotyrosine (NT, soluble Guanylate Cyclase (sGC, vasodilator-stimulated phosphoprotein (VASP, phosphorylated VASP (P-VASP and cGMP in resistance arteries were detected by immunohistochemical staining. In the present study, endothelium-dependent dilation in aging resistance arteries was lower than in those from young rats (young vs. aging: 68.0% ± 4.5% vs. 50.4% ± 2.9%, P<0.01. And the endothelium-independent dilation remained constant. Compared with young rats, aging increased nitrative stress in resistance arteries, evidenced by elevated NOx production in serum (5.3 ± 1.0 nmol/ml vs. 3.3 ± 1.4 nmol/ml, P<0.05 and increased NT expression (P<0.05. ONOO- was responsible for the vasorelaxation dysfunction, evidenced by normalized vasorelaxation after inhibit ONOO- or its sources (P<0.05 and suppressed NT expression after FeTMPyP treatment (P<0.05. The expression of sGC was not significantly different between young and aging resistance arteries, but the cGMP level and P-VASP/VASP ratio (biochemical marker of NO-sGC-cGKs signaling decreased, which was reversed by FeTMPyP treatment in vivo (P<0.05. The present study suggested that ONOO- mediated the decline of endothelium-dependent vasorelaxation of aging resistance arteries by induction of the NO-sGC-cGKs pathway dysfunction.

  8. Ca(2+) sensitisation of force production by noradrenaline in femoral conductance and resistance arteries from rats with postinfarction congestive heart failure

    DEFF Research Database (Denmark)

    Trautner, Simon; Amtorp, Ole; Boesgaard, Soren

    2006-01-01

    In this study we tested the hypothesis that arterial myofilament Ca(2+) sensitivity and/or the Ca(2+) sensitising effect of noradrenaline (NA) is enhanced in post-infarction congestive heart failure (CHF), which could contribute to the high peripheral vascular resistance in this condition. Femoral...... using wire myography and the FURA-2 fluorescence technique. In conductance and resistance arteries, the resting levels of [Ca(2+)](i) and tension in physiological saline solution (PSS) and active tension in response to single doses of 125 mM K(+) (KPSS) were unaffected by CHF. During cumulative...

  9. Systemic vascular resistance is increased and associated with accelerated arterial stiffening change in patients with chronic cervical spinal cord injury.

    Science.gov (United States)

    Huang, S C; May-Kuen Wong, A; Lien, H Y; Fuk-Tan Tang, S; Fu, T C; Lin, Y; Wang, J S

    2013-02-01

    Despite of stiffening change of conduit arteries, how total peripheral resistance (TPR) is adapted to chronic spinal cord injury (SCI) remains unclear. To investigate how chronic cervical SCI influences hemodynamic characteristics Cross-sectional, case-control study. Rehabilitation department in the tertiary medical center. Twenty-one male patients with traumatic SCI resulting from cervical spine fracture were recruited. The injury occurred three to 289 months (46 months in average) previously. Twenty-one healthy male participants with matched age and body mass index were enrolled as control group. The subjects were asked to maintain supine rest (SR) and then head-up tilt (HUT) at 60 degree for five minutes, respectively. A novel noninvasive bio-reactance device was employed to measure cardiac hemodynamics, whereas heart rate variability was used to determine cardiac autonomic activity. Additionally, the digital volume pulse analysis was applied to calculate arterial stiffness index (SI) and arteriolar reflection index (RI). SCI patients revealed less stroke volume and cardiac output (CO), as well as, greater total peripheral resistance (TPR) and SI during SR than normal subjects did. Moreover, the positive correlation between TPR and SI was observed in SCI patients rather than normal subjects. In SCI patients, HUT (1) markedly decreased TPR while CO and cardio-acceleration responses remained intact and (2) decreased HF power value but failed to change LF/HF ratio. Furthermore, the degree of orthostatic hypotension was correlated with the TPRHUT/TPRSR ratio but not the COHUT/COSR ratio. Chronic cervical SCI leads to a progressively accelerated increase in vascular stiffness, which is associated with increase in systemic vascular resistance. Furthermore, the cervical SCI-related orthostatic hypotension lies in the impairment of vasoconstriction without cardiac dysfunction. Clinical Rehabilitation Impact. SI, rather than blood pressure, reflects not only

  10. Treatment of secondary hyperparathyroidism by high calcium diet is associated with enhanced resistance artery relaxation in experimental renal failure.

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    Jolma, Pasi; Kööbi, Peeter; Kalliovalkama, Jarkko; Saha, Heikki; Fan, Meng; Jokihaara, Jarkko; Moilanen, Eeva; Tikkanen, Ilkka; Pörsti, Ilkka

    2003-12-01

    Vasorelaxation is impaired in renal failure (RF) and hypertension. A high calcium diet enhances vasodilatation and reduces blood pressure in experimental hypertension. Oral calcium salts are used as phosphate binders in RF. However, the effect of increased calcium intake on arterial tone in RF is unknown. We investigated the influence of an 8-week high calcium diet (0.3 vs 3.0%) on resistance artery tone in 5/6 nephrectomized (NTX) rats. Calcium was supplemented as carbonate salt, blood pressure measured by tail-cuff, urine collected in metabolic cages, and samples taken for blood chemistry and parathyroid hormone (PTH). Functional studies of isolated third-order branches of the mesenteric artery in vitro were performed using the Mulvany multimyograph. Plasma urea was elevated 1.6-fold and systolic blood pressure by 10 mmHg after NTX, while increased calcium intake was without effect on these variables. Plasma PTH and phosphate were raised following NTX, and suppressed by high calcium diet. Vasorelaxations induced by K(+) channel agonists 11,12-epoxyeicosatrienoic acid and levcromakalim were impaired after NTX. Vasorelaxation induced by acetylcholine was also reduced following NTX, and experiments with N(G)-nitro-L-arginine methyl ester, diclofenac and charybdotoxin + apamin suggested that the K(+) channel-mediated component of endothelium-dependent relaxation was deficient after NTX. Increased calcium intake corrected all impairments of vasodilatation in NTX rats. Deficient vasorelaxation via K(+) channels was normalized by high calcium diet in experimental RF. This effect was independent of the degree of renal impairment and blood pressure, but was associated with improved calcium metabolism: plasma levels of PTH and phosphate were decreased and ionized calcium was increased.

  11. A cyclic GMP-dependent calcium-activated chloride current in smooth-muscle cells from rat mesenteric resistance arteries

    DEFF Research Database (Denmark)

    Matchkov, Vladimir; Aalkjær, Christian; Nilsson, Holger

    2004-01-01

    M) in the pipette solution. The current was found to be a calcium-activated chloride current with an absolute requirement for cyclic GMP (EC50 6.4 microM). The current could be activated by the constitutively active subunit of PKG. Current activation was blocked by the protein kinase G antagonist Rp-8-Br......We have previously demonstrated the presence of a cyclic GMP (cGMP)-dependent calcium-activated inward current in vascular smooth-muscle cells, and suggested this to be of importance in synchronizing smooth-muscle contraction. Here we demonstrate the characteristics of this current. Using...... conventional patch-clamp technique, whole-cell currents were evoked in freshly isolated smooth-muscle cells from rat mesenteric resistance arteries by elevation of intracellular calcium with either 10 mM caffeine, 1 microM BAY K8644, 0.4 microM ionomycin, or by high calcium concentration (900 n...

  12. Evaluation of an isotope washout technique to measure skin vascular resistance and skin perfusion pressure: influence of age, site and arterial surgery

    International Nuclear Information System (INIS)

    Duncan, H.J.; Faris, I.B.

    1986-01-01

    1. A simplified isotope (sup(99m)Tc) washout technique has been devised to calculate the skin perfusion pressure (SPP) and skin vascular resistance (SVR). This test is simple, requires inexpensive equipment and is well tolerated by patients. 2. SPP and SVR were calculated in 20 patients 30 years of age and in 15 patients with peripheral vascular disease (PVD). With increasing age the SPP and SVP were increased. The SPP was similar to the mean arterial pressure in normal individuals but was decreased in patients with PVD. The SPP is a useful indicator of the severity of the PVD. 3. The SPP and SVR were higher in the calf than in the foot. This is probably related to the decrease in pressure in the distal arterial tree. 4. SPP was increased by 110% and skin blood flow by 190% by arterial reconstructive surgery. This test may be of use in assessing the effectiveness of arterial surgery. (author)

  13. Ultrasound-assessed perirenal fat is related to increased ophthalmic artery resistance index in HIV-1 patients

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    Chiavaroli Roberto

    2010-06-01

    Full Text Available Abstract Background The introduction of highly active antiretroviral therapy (HAART has dramatically changed the prognosis of human immunodeficiency virus (HIV infection, with a significant decline in morbidity and mortality. Changes in body fat distribution are a common finding in individuals with HIV infection being treated with antiretrovirals, and this condition (collectively termed lipodystrophy syndrome is associated with depletion of subcutaneous fat, increased triglycerides and insulin resistance. Obesity, particularly visceral obesity, is associated with increased risk of cardiovascular disease. Therefore, estimating visceral fat distribution is important in identifying subjects at high risk for cardiovascular disease. The aim of our study was to evaluate whether perirenal fat thickness (PRFT, a parameter of central obesity, is related to ophthalmic artery resistance index (OARI, an index of occlusive carotid artery disease in HIV-1 infected patients. Methods We enrolled 88 consecutive HIV-1-infected patients receiving highly active antiretroviral therapy for more than 12 months, in a prospective cohort study. Echographically measured PRFT and OARI, as well as serum metabolic parameters, were evaluated. PRFT and OARI were measured by 3.75 MHz convex and 7.5 MHz linear probe, respectively. Results The means of PRFT and OARI in HIV-1-infected patients with visceral obesity was considerably higher than in patients without it (p 0.74 (sensitivity 78.9%, specificity 82.8%. Conclusions Our data indicate that ultrasound assessment of PRFT may have potential as a marker of increased endothelial damage with specific involvement of the ocular vascular region in HIV-1-infected patients.

  14. Critical contribution of Na+-Ca2+ exchanger to the Ca2+-mediated vasodilation activated in endothelial cells of resistance arteries.

    Science.gov (United States)

    Lillo, Mauricio A; Gaete, Pablo S; Puebla, Mariela; Ardiles, Nicolás M; Poblete, Inés; Becerra, Alvaro; Simon, Felipe; Figueroa, Xavier F

    2018-04-01

    Na + -Ca 2+ exchanger (NCX) contributes to control the intracellular free Ca 2+ concentration ([Ca 2+ ] i ), but the functional activation of NCX reverse mode (NCXrm) in endothelial cells is controversial. We evaluated the participation of NCXrm-mediated Ca 2+ uptake in the endothelium-dependent vasodilation of rat isolated mesenteric arterial beds. In phenylephrine-contracted mesenteries, the acetylcholine (ACh)-induced vasodilation was abolished by treatment with the NCXrm blockers SEA0400, KB-R7943, or SN-6. Consistent with that, the ACh-induced hyperpolarization observed in primary cultures of mesenteric endothelial cells and in smooth muscle of isolated mesenteric resistance arteries was attenuated by KB-R7943 and SEA0400, respectively. In addition, both blockers abolished the NO production activated by ACh in intact mesenteric arteries. In contrast, the inhibition of NCXrm did not affect the vasodilator responses induced by the Ca 2+ ionophore, ionomycin, and the NO donor, S-nitroso- N-acetylpenicillamine. Furthermore, SEA0400, KB-R7943, and a small interference RNA directed against NCX1 blunted the increase in [Ca 2+ ] i induced by ACh or ATP in cultured endothelial cells. The analysis by proximity ligation assay showed that the NO-synthesizing enzyme, eNOS, and NCX1 were associated in endothelial cell caveolae of intact mesenteric resistance arteries. These results indicate that the activation of NCXrm has a central role in Ca 2+ -mediated vasodilation initiated by ACh in endothelial cells of resistance arteries.-Lillo, M. A., Gaete, P. S., Puebla, M., Ardiles, N. M., Poblete, I., Becerra, A., Simon, F., Figueroa, X. F. Critical contribution of Na + -Ca 2+ exchanger to the Ca 2+ -mediated vasodilation activated in endothelial cells of resistance arteries.

  15. Impact of Cardiac Contractility during Cerebral Blood Flow in Ischemia

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    Silver, Brian

    2011-05-01

    Full Text Available Objective: In cerebral regions affected by ischemia, intrinsic vascular autoregulation is often lost. Blood flow delivery depends upon cardiac function and may be influenced by neuro-endocrine mediated myocardial suppression. Our objective is to evaluate the relation between ejection fraction (EF and transcranial doppler (TCD peak systolic velocities (PSV in patients with cerebral ischemic events.Methods: We conducted a retrospective cohort study from an existing TCD registry. We evaluated patients admitted within 24 hours of onset of a focal neurological deficit who had an echocardiogram and TCD performed within 72 hours of admission.Results: We identified 58 patients from March to October 2003. Eighty-one percent (n=47 had a hospital discharge diagnosis of ischemic stroke and 18.9% (n=11 had a diagnosis of transient ischemic attack. Fourteen patients had systolic dysfunction (EF50% compared to those with systolic dysfunction (EF<50% was as follows: middle cerebral artery 62.0 + 28.6 cm/s vs. 51.0 + 23.3 cm/s, p=0.11; anterior cerebral artery 52.1 + 21.6 cm/s vs. 45.9 + 22.7 cm/s, p=0.28; internal carotid artery 56.5 + 20.1 cm/s vs. 46.4 + 18.4 cm/s, p=0.04; ophthalmic artery 18.6 + 7.2 cm/s vs. 15.3 + 5.2 cm/s, p=0.11; vertebral artery 34.0 + 13.9 cm/s vs. 31.6 + 15.0 cm/s, p=0.44.Conclusion: Cerebral blood flow in the internal carotid artery territory appears to be higher in cerebral ischemia patients with preserved left ventricular contractility. Our study was unable to differentiate pre-existing cardiac dysfunction from neuro-endocrine mediated myocardial stunning. Future research is necessary to better understand heart-brain interactions in this setting and to further explore the underlying mechanisms and consequences of neuro-endocrine mediated cardiac dysfunction. [West J Emerg Med. 2011;12(2:227-232.

  16. The prevalence of resistant arterial hypertension and secondary causes in a cohort of hypertensive patients: a single center experience

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    Luigi Petramala

    2017-11-01

    Full Text Available The prevalence of resistant hypertension (RHT still remains unknown. Aim of the study was to investigate in a large cohort of hypertensive patients the prevalence of RHT, and to identify in these patients the secondary forms of arterial hypertension (SH. We enrolled a series of 3685 consecutive hypertensive patients. All patients underwent complete physical examination, laboratory tests, screening for SH. Ambulatory blood pressure monitoring (ABPM was performed to exclude white-coat hypertension. Further, we investigated for any obstructive sleep apnea syndrome (OSA. Only 232 (5.8% hypertensive patients fulfilled criteria for RHT. 91 (39% had a SH; 56 (61% hypertensive patients had a primary aldosteronism, 22 (24% had OSA, 7 (7.7% had a hypercortisolism, and 5 (5.5% had a renovascular hypertension (RVH. Only one patient had adrenal pheochromocytoma. An accurate definition and investigation into RHT is needed. We recommend ABPM to all patients at diagnosis. Finally, all patients must be screened for SH, such as adrenal hypertension, OSA and RVH, especially those who are apparently resistant to polypharmacological treatment.

  17. Is heart rate variability a feasible method to determine anaerobic threshold in progressive resistance exercise in coronary artery disease?

    Science.gov (United States)

    Sperling, Milena P R; Simões, Rodrigo P; Caruso, Flávia C R; Mendes, Renata G; Arena, Ross; Borghi-Silva, Audrey

    2016-01-01

    Recent studies have shown that the magnitude of the metabolic and autonomic responses during progressive resistance exercise (PRE) is associated with the determination of the anaerobic threshold (AT). AT is an important parameter to determine intensity in dynamic exercise. To investigate the metabolic and cardiac autonomic responses during dynamic resistance exercise in patients with Coronary Artery Disease (CAD). Twenty men (age = 63±7 years) with CAD [Left Ventricular Ejection Fraction (LVEF) = 60±10%] underwent a PRE protocol on a leg press until maximal exertion. The protocol began at 10% of One Repetition Maximum Test (1-RM), with subsequent increases of 10% until maximal exhaustion. Heart Rate Variability (HRV) indices from Poincaré plots (SD1, SD2, SD1/SD2) and time domain (rMSSD and RMSM), and blood lactate were determined at rest and during PRE. Significant alterations in HRV and blood lactate were observed starting at 30% of 1-RM (p<0.05). Bland-Altman plots revealed a consistent agreement between blood lactate threshold (LT) and rMSSD threshold (rMSSDT) and between LT and SD1 threshold (SD1T). Relative values of 1-RM in all LT, rMSSDT and SD1T did not differ (29%±5 vs 28%±5 vs 29%±5 Kg, respectively). HRV during PRE could be a feasible noninvasive method of determining AT in CAD patients to plan intensities during cardiac rehabilitation.

  18. Doppler evaluation of intrathyroid arterial resistances during preoperative treatment with Lugol's iodide solution in patients with diffuse toxic goiter.

    Science.gov (United States)

    Ansaldo, G L; Pretolesi, F; Varaldo, E; Meola, C; Minuto, M; Borgonovo, G; Derchi, L E; Torre, G C

    2000-12-01

    The aim of this study was to ascertain the utility of echo-Doppler in the analysis of the low resistance thyroid vascularization in diffuse toxic goiter (DTG), and the effectiveness of Lugol's solution (iodine-iodide solution) in patients undergoing thyroidectomy. Twenty-five patients with diffuse toxic goiter were evaluated and compared with 19 normal subjects. Patients were treated with increasing doses of Lugol's solution 2% for 7 days until a total dose of 75 mg of iodine was given. Echo-Doppler was performed on the last day of treatment, 12 hours before operation. Mean basal Doppler Resistance Index (RI) of intrathyroid arterial flow was significantly lower in patients with DTG compared with normal controls (0.4718 +/- 0.0625 versus 0.55 +/- 0.05, range: 0.472 to 0.643; p = 0.008). Moreover, the RI was significantly increased in patients with DTG after Lugol's solution (+16.46 +/- 10.22%, range: -2.59 to +39.97; pLugol's solution therapy induces normalization of those changes for safer thyroidectomy.

  19. Actomyosin contractility rotates the cell nucleus

    Science.gov (United States)

    Kumar, Abhishek; Maitra, Ananyo; Sumit, Madhuresh; Ramaswamy, Sriram; Shivashankar, G. V.

    2014-01-01

    The cell nucleus functions amidst active cytoskeletal filaments, but its response to their contractile stresses is largely unexplored. We study the dynamics of the nuclei of single fibroblasts, with cell migration suppressed by plating onto micro-fabricated patterns. We find the nucleus undergoes noisy but coherent rotational motion. We account for this observation through a hydrodynamic approach, treating the nucleus as a highly viscous inclusion residing in a less viscous fluid of orientable filaments endowed with active stresses. Lowering actin contractility selectively by introducing blebbistatin at low concentrations drastically reduced the speed and coherence of the angular motion of the nucleus. Time-lapse imaging of actin revealed a correlated hydrodynamic flow around the nucleus, with profile and magnitude consistent with the results of our theoretical approach. Coherent intracellular flows and consequent nuclear rotation thus appear to be an intrinsic property of cells. PMID:24445418

  20. Effects of the use of assisted reproductive technologies and an obesogenic environment on resistance artery function and diabetes biomarkers in mice offspring.

    Directory of Open Access Journals (Sweden)

    Francisco I Ramirez-Perez

    Full Text Available Maternal obesity affects the incidence of cardiovascular disease and diabetes in offspring. Also the use of assisted reproductive technologies (ART has been associated with cardiovascular deficiencies in offspring. Obese women often suffer from infertility and use ART to achieve a pregnancy, but the combined effects of maternal obesity and ART on cardiovascular health and incidence of diabetes in the offspring is not known. Here, we report the effects of the use of ART within an obesogenic environment, consisting of feeding a western diet (WD to dams and offspring, on resistance artery function and presence of diabetes biomarkers in juvenile mice offspring. Our results indicate that WD and ART interacted to induce endothelial dysfunction in mesenteric resistance arteries isolated from 7-week-old mice offspring. This was determined by presence of a reduced acetylcholine-induced dilation compared to controls. The arteries from these WD-ART mice also had greater wall cross-sectional areas and wall to lumen ratios indicative of vascular hypertrophic remodeling. Of the diabetes biomarkers measured, only resistin was affected by a WD×ART interaction. Serum resistin was significantly greater in WD-ART offspring compared to controls. Diet and sex effects were observed in other diabetes biomarkers. Our conclusion is that in mice the use of ART within an obesogenic environment interacts to favor the development of endothelial dysfunction in the resistance arteries of juvenile offspring, while having marginal effects on diabetes biomarkers.

  1. Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639

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    Gasparovic Hrvoje

    2012-08-01

    Full Text Available Abstract Background Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive. The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events. Methods Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology as well as bleeding events will be recorded. Discussion This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management. This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639.

  2. Contractile network models for adherent cells.

    Science.gov (United States)

    Guthardt Torres, P; Bischofs, I B; Schwarz, U S

    2012-01-01

    Cells sense the geometry and stiffness of their adhesive environment by active contractility. For strong adhesion to flat substrates, two-dimensional contractile network models can be used to understand how force is distributed throughout the cell. Here we compare the shape and force distribution for different variants of such network models. In contrast to Hookean networks, cable networks reflect the asymmetric response of biopolymers to tension versus compression. For passive networks, contractility is modeled by a reduced resting length of the mechanical links. In actively contracting networks, a constant force couple is introduced into each link in order to model contraction by molecular motors. If combined with fixed adhesion sites, all network models lead to invaginated cell shapes, but only actively contracting cable networks lead to the circular arc morphology typical for strongly adhering cells. In this case, shape and force distribution are determined by local rather than global determinants and thus are suited to endow the cell with a robust sense of its environment. We also discuss nonlinear and adaptive linker mechanics as well as the relation to tissue shape. © 2012 American Physical Society

  3. Association Between the P2RY12 Receptor Gene Polymorphism and Aspirin Resistance in Patients with Coronary Artery Disease

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    Ludmila Karazhanova

    2014-12-01

    Full Text Available Introduction. Platelet activation and aggregation are key elements in the development of coronary atherosclerosis. Recent studies have shown that the two polymorphisms of platelet ADP receptor P2RY12 (haplotypes H2 and 34T are associated with increased platelet aggregation and atherothrombotic risk. It was shown that these polymorphisms promote reduced body response to antiplatelet therapy.Aim. We investigated the association of P2RY12 gene polymorphisms with aspirin resistance in patients with coronary artery disease (CAD.Methods. This case-control study included 100 cases with CAD (mean age 57.6 ± 2.8 years treated in the cardiology department of the city hospital Semey, Kazakhstan, 90 of whom suffered from myocardial infarction. The control group (n = 100 were healthy people without a history of CAD, matched on sex and age. Genotyping of polymorphisms H1/H2 in P2RY12 gene was performed by PCR. Statistical analysis was performed using SPSS v.19.0.Results. The distribution of H1/H2 genotypes P2RY12 was 42%, 34%, and 24%, respectively, in cases and 42%, 58%, and 0%, respectively, in controls. All allele frequencies were consistent with the Hardy Weinberg equilibrium (p = 0.0036 and p = 0.0001 in cases and controls, respectively. Genotype H2 was associated with risk of CAD with aspirin resistance (co-dominant model: OR = 3.75, 95% CI 0.14 - 99.88, p = 0.05 and dominant model: OR = 2.78, 95% CI 0.11 - 70.93, p = 0.05. We found significant differences in the distribution of the mutant genotype H2 between CAD patients with aspirin resistance and healthy controls (χ2 = 30.3, p < 0.05.Conclusion. We found an association of H2 haplotype in P2RY12 gene with aspirin resistance in patients with CAD. However, in order to obtain definitive conclusions about the role of genetic variants with the development of aspirin resistance in patients with CAD, there is a need for further research with a larger sample size as well as the use of selective thromboxane

  4. Suction/Inspiration against resistance or standardized Mueller maneuver : a new breathing technique to improve contrast density within the pulmonary artery: a pilot CT study.

    Science.gov (United States)

    Gutzeit, Andreas; Froehlich, Johannes M; Wälti, Stephan; Roos, Justus E; Meissnitzer, Matthias; Hergan, Klaus; von Weymarn, Constantin; Czell, David; Goyen, Matthias; Reischauer, Carolin

    2015-11-01

    Our aim was to prospectively investigate whether the recently introduced suction/inspiration against resistance breathing method leads to higher computed tomography (CT) contrast density in the pulmonary artery compared to standard breathing. The present study was approved by the Medical Ethics committee and all subjects gave written informed consent. Fifteen patients, each without suspicious lung emboli, were randomly assigned to four different groups with different breathing maneuvers (suction against resistance, Valsalva, inspiration, expiration) during routine CT. Contrast enhancement in the central and peripheral sections of the pulmonary artery were measured and compared with one another. Peripheral enhancement during suction yielded increased mean densities of 138.14 Hounsfield units (HU) (p = 0.001), compared to Valsalva and a mean density of 67.97 HU superior to inspiration (p = 0.075). Finally, suction in comparison to expiration resulted in a mean increase of 30.51 HU (p = 0.42). Central parts of pulmonary arteries presented significantly increased enhancement values (95.74 HU) for suction versus the Valsalva technique (p = 0.020), while all other mean densities were in favour of suction (versus inspiration: p = 0.201; versus expiration: p = 0.790) without reaching significance. Suction/Inspiration against resistance is a promising technique to improve contrast density within pulmonary vessels, especially in the peripheral parts, in comparison to other breathing maneuvers. • Suction/Inspiration against resistance is promising to improve contrast density within the pulmonary artery. • Patients potentially suffering pulmonary embolism are able to follow suction/inspiration against resistance. • Contrast density after suction is superior in comparison to other breathing maneuvers.

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

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    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.

  6. Prediction of neonatal respiratory distress syndrome in term pregnancies by assessment of fetal lung volume and pulmonary artery resistance index.

    Science.gov (United States)

    Laban, Mohamed; Mansour, Ghada M; Elsafty, Mohammed S E; Hassanin, Alaa S; EzzElarab, Sahar S

    2015-03-01

    To develop reference cutoff values for mean fetal lung volume (FLV) and pulmonary artery resistance index (PA-RI) for prediction of neonatal respiratory distress syndrome (RDS) in low-risk term pregnancies. As part of a cross-sectional study, women aged 20-35 years were enrolled and admitted to a tertiary hospital in Cairo, Egypt, for elective repeat cesarean at 37-40 weeks of pregnancy between January 1, 2012, and July 31, 2013. FLV was calculated by virtual organ computer-aided analysis, and PA-RI was measured by Doppler ultrasonography before delivery. A total of 80 women were enrolled. Neonatal RDS developed in 11 (13.8%) of the 80 newborns. Compared with neonates with RDS, healthy neonates had significantly higher FLVs (P<0.001) and lower PA-RIs (P<0.001). Neonatal RDS is less likely with FLV of at least 32 cm(3) or PA-RI less than or equal to 0.74. Combining these two measures improved the accuracy of prediction. The use of either FLV or PA-RI predicted neonatal RDS. The predictive value increased when these two measures were combined. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Cell stiffness, contractile stress and the role of extracellular matrix

    International Nuclear Information System (INIS)

    An, Steven S.; Kim, Jina; Ahn, Kwangmi; Trepat, Xavier; Drake, Kenneth J.; Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne; Fredberg, Jeffrey J.; Biswal, Shyam

    2009-01-01

    Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

  8. Cell stiffness, contractile stress and the role of extracellular matrix

    Energy Technology Data Exchange (ETDEWEB)

    An, Steven S., E-mail: san@jhsph.edu [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Kim, Jina [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Ahn, Kwangmi [Division of Biostatistics, Penn State College of Medicine, Hershey, PA 17033 (United States); Trepat, Xavier [CIBER, Enfermedades Respiratorias, 07110 Bunyola (Spain); Drake, Kenneth J. [Division of Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 (United States); Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Fredberg, Jeffrey J. [Division of Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 (United States); Biswal, Shyam [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205 (United States)

    2009-05-15

    Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

  9. Modeling the dispersion effects of contractile fibers in smooth muscles

    Science.gov (United States)

    Murtada, Sae-Il; Kroon, Martin; Holzapfel, Gerhard A.

    2010-12-01

    Micro-structurally based models for smooth muscle contraction are crucial for a better understanding of pathological conditions such as atherosclerosis, incontinence and asthma. It is meaningful that models consider the underlying mechanical structure and the biochemical activation. Hence, a simple mechanochemical model is proposed that includes the dispersion of the orientation of smooth muscle myofilaments and that is capable to capture available experimental data on smooth muscle contraction. This allows a refined study of the effects of myofilament dispersion on the smooth muscle contraction. A classical biochemical model is used to describe the cross-bridge interactions with the thin filament in smooth muscles in which calcium-dependent myosin phosphorylation is the only regulatory mechanism. A novel mechanical model considers the dispersion of the contractile fiber orientations in smooth muscle cells by means of a strain-energy function in terms of one dispersion parameter. All model parameters have a biophysical meaning and may be estimated through comparisons with experimental data. The contraction of the middle layer of a carotid artery is studied numerically. Using a tube the relationships between the internal pressure and the stretches are investigated as functions of the dispersion parameter, which implies a strong influence of the orientation of smooth muscle myofilaments on the contraction response. It is straightforward to implement this model in a finite element code to better analyze more complex boundary-value problems.

  10. Umbilical artery tone in maternal obesity

    OpenAIRE

    Hehir, Mark P; Moynihan, Audrey T; Glavey, Siobhan V; Morrison, John J

    2009-01-01

    Abstract Background The increasing prevalence of obesity constitutes a major health problem in obstetrics with implications for feto-maternal growth and wellbeing. This study investigated and compared the contractile properties of umbilical arteries excised from obese women, with those excised from women with a normal body mass index (BMI). Methods Sections of umbilical artery were obtained from umbilical cord samples immediately after delivery and mounted for isometric recording in organ tis...

  11. [Resistant arterial hypertension in Primary Care patients in Spain. PRESCAP Study 2010].

    Science.gov (United States)

    Cinza-Sanjurjo, S; Alonso-Moreno, F J; Prieto-Díaz, M Á; Divisón-Garrote, J A; Rodríguez-Roca, G C; Llisterri-Caro, J L

    2015-04-01

    To determine the prevalence and clinical and epidemiological characteristics of Primary Care patients with resistant hypertension (RHT) in Spain. A cross-sectional multicenter study was conducted on hypertensive patients aged 18 or over and seen in a Primary Care clinic. RHT was considered as the presence of uncontrolled blood pressure in patients treated with at least 3 drugs, one of which is a diuretic. Of the 12,961 hypertensive patients in the PRESCAP 2010 study, 962 (7.4%) fulfilled criteria for RHT, of whom 51% were women, and with a mean age (SD) 68.8 [11.4] years. Patients with RHT were older (68.80 [10.69] years vs. 66.06 [11.44] years, Pdiabetes mellitus, sedentary life style, microalbuminuria, body mass index, duration of AHT, and triglycerides. The prevalence of RHT in Primary Care patients is related to inappropriate lifestyles, the presence of target organ damage, and cardiovascular disease. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  12. Suction/inspiration against resistance or standardized Mueller maneuver: a new breathing technique to improve contrast density within the pulmonary artery: a pilot CT study

    International Nuclear Information System (INIS)

    Gutzeit, Andreas; Froehlich, Johannes M.; Weymarn, Constantin von; Goyen, Matthias; Waelti, Stephan; Roos, Justus E.; Meissnitzer, Matthias; Hergan, Klaus; Czell, David; Reischauer, Carolin

    2015-01-01

    Our aim was to prospectively investigate whether the recently introduced suction/inspiration against resistance breathing method leads to higher computed tomography (CT) contrast density in the pulmonary artery compared to standard breathing. The present study was approved by the Medical Ethics committee and all subjects gave written informed consent. Fifteen patients, each without suspicious lung emboli, were randomly assigned to four different groups with different breathing maneuvers (suction against resistance, Valsalva, inspiration, expiration) during routine CT. Contrast enhancement in the central and peripheral sections of the pulmonary artery were measured and compared with one another. Peripheral enhancement during suction yielded increased mean densities of 138.14 Hounsfield units (HU) (p = 0.001), compared to Valsalva and a mean density of 67.97 HU superior to inspiration (p = 0.075). Finally, suction in comparison to expiration resulted in a mean increase of 30.51 HU (p = 0.42). Central parts of pulmonary arteries presented significantly increased enhancement values (95.74 HU) for suction versus the Valsalva technique (p = 0.020), while all other mean densities were in favour of suction (versus inspiration: p = 0.201; versus expiration: p = 0.790) without reaching significance. Suction/Inspiration against resistance is a promising technique to improve contrast density within pulmonary vessels, especially in the peripheral parts, in comparison to other breathing maneuvers. (orig.)

  13. Suction/inspiration against resistance or standardized Mueller maneuver: a new breathing technique to improve contrast density within the pulmonary artery: a pilot CT study

    Energy Technology Data Exchange (ETDEWEB)

    Gutzeit, Andreas [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Hirslanden Hospital St. Anna, Institute of Radiology and Nuclear Medicine, Clinical Research Unit, Lucerne (Switzerland); Kantonsspital Winterthur, Department of Radiology, Winterthur (Switzerland); Froehlich, Johannes M.; Weymarn, Constantin von; Goyen, Matthias [Hirslanden Hospital St. Anna, Institute of Radiology and Nuclear Medicine, Clinical Research Unit, Lucerne (Switzerland); Waelti, Stephan [Cantonal Hospital St. Gallen, Department of Radiology and Nuclear Medicine, St. Gallen (Switzerland); Roos, Justus E. [Duke University Medical Center, Department of Radiology, Durham, NC (United States); Meissnitzer, Matthias; Hergan, Klaus [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Czell, David [Cantonal Hospital Winterthur, Department of Neurology, Winterthur (Switzerland); Reischauer, Carolin [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Hirslanden Hospital St. Anna, Institute of Radiology and Nuclear Medicine, Clinical Research Unit, Lucerne (Switzerland)

    2015-11-15

    Our aim was to prospectively investigate whether the recently introduced suction/inspiration against resistance breathing method leads to higher computed tomography (CT) contrast density in the pulmonary artery compared to standard breathing. The present study was approved by the Medical Ethics committee and all subjects gave written informed consent. Fifteen patients, each without suspicious lung emboli, were randomly assigned to four different groups with different breathing maneuvers (suction against resistance, Valsalva, inspiration, expiration) during routine CT. Contrast enhancement in the central and peripheral sections of the pulmonary artery were measured and compared with one another. Peripheral enhancement during suction yielded increased mean densities of 138.14 Hounsfield units (HU) (p = 0.001), compared to Valsalva and a mean density of 67.97 HU superior to inspiration (p = 0.075). Finally, suction in comparison to expiration resulted in a mean increase of 30.51 HU (p = 0.42). Central parts of pulmonary arteries presented significantly increased enhancement values (95.74 HU) for suction versus the Valsalva technique (p = 0.020), while all other mean densities were in favour of suction (versus inspiration: p = 0.201; versus expiration: p = 0.790) without reaching significance. Suction/Inspiration against resistance is a promising technique to improve contrast density within pulmonary vessels, especially in the peripheral parts, in comparison to other breathing maneuvers. (orig.)

  14. Individual blood pressure responses to walking and resistance exercise in peripheral artery disease patients: Are the mean values describing what is happening?

    Science.gov (United States)

    Lima, Aluísio H R A; Miranda, Alessandra S; Correia, Marilia A; Soares, Antônio H G; Cucato, Gabriel G; Sobral Filho, Dario C; Gomes, Silvana L; Ritti-Dias, Raphael M

    2015-12-01

    The aim of this study was to analyze the average and individual blood pressure responses to walking and resistance exercise in patients with peripheral artery disease. Thirteen patients underwent three experimental sessions: walking exercise, resistance exercise, and control. Ambulatory blood pressure, heart rate, and rate pressure product were obtained before and until 24 hours after sessions. The mean cardiovascular values during 24 hours, awake, and sleep periods were similar (P > 0.05) after the three experimental sessions. The analysis of individual data revealed that during 24 hours, eight of 13 patients reduced systolic or diastolic blood pressure in ≥4.0 mm Hg in at least one of the exercise session; furthermore, most of these patients presented greater responses after resistance exercise. The clinical characteristics of patients seem to influence the blood pressure responses after exercises. Individual data showed that part of patients presented clinically significant decreases in blood pressure, showing that these patients have acute cardiovascular benefits after performing an acute bout of exercise. Although, in average, a bout of walking or resistance exercise did not decrease ambulatory blood pressure in peripheral artery disease patients, the individual data revealed that most patients presented clinically relevant blood pressure reductions, especially after resistance exercise. Copyright © 2015 Society for Vascular Nursing, Inc. Published by Elsevier Inc. All rights reserved.

  15. [Ability to Overcome the Thrombocyte Resistance to Acetylsalicylic Acid in Patients With Coronary Artery Disease After Myocardial Revascularization With Coronary Stenting].

    Science.gov (United States)

    Pershukov, I V; Ostaschenko, S L; Kuznetsova, T N; Scherbo, S N; Karben, Z A; Sokryukina, E V; Omarov, A A; Ramazanov, D M; Bosak, N V; Shulzhenko, L V; Kalmatov, R K; Batyraliev, T A; Sidorenko, B A

    2016-07-01

    Resistance to acetylsalicylic acid (ASA) in patients with coronary artery disease is a poor predictor for the development of atherothrombotic complications. In 277 patients with coronary artery disease suffered uncomplicated coronary angioplasty with stent implantation, we was estimated arachidon-induced platelet aggregation during treatment with acetylsalicylic acid by bedside VerifyNow Assay test at 28-90 days after the intervention. It was found that 18.9% of the 144 patients receiving a combination of ASA 75 mg with 15.2 mg of magnesium hydroxide had true (laboratory) resistance to ASA. At the same time on the original enteric coated ASA 100 mg, we can found only 0.8% resistance to ASA among 129 patients. We made switch from combination of ASA 75 mg with 15.2 mg of magnesium hydroxide to original enteric coated ASA 100 mg and repeat VerifyNow Assay test at 2-4 days and found lost of resistance in 92% of 28 patients. Thus, resistance to the ASA is not constant, it depends on the form and the applied dose of ASA, and eliminating more than 92% when ASA changes from ineffective to effective form.

  16. Cadmium translocation by contractile roots differs from that in regular, non-contractile roots.

    Science.gov (United States)

    Lux, Alexander; Lackovič, Andrej; Van Staden, Johannes; Lišková, Desana; Kohanová, Jana; Martinka, Michal

    2015-06-01

    Contractile roots are known and studied mainly in connection with the process of shrinkage of their basal parts, which acts to pull the shoot of the plant deeper into the ground. Previous studies have shown that the specific structure of these roots results in more intensive water uptake at the base, which is in contrast to regular root types. The purpose of this study was to find out whether the basal parts of contractile roots are also more active in translocation of cadmium to the shoot. Plants of the South African ornamental species Tritonia gladiolaris were cultivated in vitro for 2 months, at which point they possessed well-developed contractile roots. They were then transferred to Petri dishes with horizontally separated compartments of agar containing 50 µmol Cd(NO3)2 in the region of the root base or the root apex. Seedlings of 4-d-old maize (Zea mays) plants, which do not possess contractile roots, were also transferred to similar Petri dishes. The concentrations of Cd in the leaves of the plants were compared after 10 d of cultivation. Anatomical analyses of Tritonia roots were performed using appropriately stained freehand cross-sections. The process of contraction required specific anatomical adaptation of the root base in Tritonia, with less lignified and less suberized tissues in comparison with the subapical part of the root. These unusual developmental characteristics were accompanied by more intensive translocation of Cd ions from the basal part of contractile roots to the leaves than from the apical-subapical root parts. The opposite effects were seen in the non-contractile roots of maize, with higher uptake and transport by the apical parts of the root and lower uptake and transport by the basal part. The specific characteristics of contractile roots may have a significant impact on the uptake of ions, including toxic metals from the soil surface layers. This may be important for plant nutrition, for example in the uptake of nutrients from

  17. Molecular Regulation of Arterial Aneurysms: Role of Actin Dynamics and microRNAs in Vascular Smooth Muscle

    Directory of Open Access Journals (Sweden)

    Azra Alajbegovic

    2017-08-01

    Full Text Available Aortic aneurysms are defined as an irreversible increase in arterial diameter by more than 50% relative to the normal vessel diameter. The incidence of aneurysm rupture is about 10 in 100,000 persons per year and ruptured arterial aneurysms inevitably results in serious complications, which are fatal in about 40% of cases. There is also a hereditary component of the disease and dilation of the ascending thoracic aorta is often associated with congenital heart disease such as bicuspid aortic valves (BAV. Furthermore, specific mutations that have been linked to aneurysm affect polymerization of actin filaments. Polymerization of actin is important to maintain a contractile phenotype of smooth muscle cells enabling these cells to resist mechanical stress on the vascular wall caused by the blood pressure according to the law of Laplace. Interestingly, polymerization of actin also promotes smooth muscle specific gene expression via the transcriptional co-activator MRTF, which is translocated to the nucleus when released from monomeric actin. In addition to genes encoding for proteins involved in the contractile machinery, recent studies have revealed that several non-coding microRNAs (miRNAs are regulated by this mechanism. The importance of these miRNAs for aneurysm development is only beginning to be understood. This review will summarize our current understanding about the influence of smooth muscle miRNAs and actin polymerization for the development of arterial aneurysms.

  18. Contractile Dysfunction in Sarcomeric Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    MacIver, David H; Clark, Andrew L

    2016-09-01

    The pathophysiological mechanisms underlying the clinical phenotype of sarcomeric hypertrophic cardiomyopathy are controversial. The development of cardiac hypertrophy in hypertension and aortic stenosis is usually described as a compensatory mechanism that normalizes wall stress. We suggest that an important abnormality in hypertrophic cardiomyopathy is reduced contractile stress (the force per unit area) generated by myocardial tissue secondary to abnormalities such as cardiomyocyte disarray. In turn, a progressive deterioration in contractile stress provokes worsening hypertrophy and disarray. A maintained or even exaggerated ejection fraction is explained by the increased end-diastolic wall thickness producing augmented thickening. We propose that the nature of the hemodynamic load in an individual with hypertrophic cardiomyopathy could determine its phenotype. Hypertensive patients with hypertrophic cardiomyopathy are more likely to develop exaggerated concentric hypertrophy; athletic individuals an asymmetric pattern; and inactive individuals a more apical hypertrophy. The development of a left ventricular outflow tract gradient and mitral regurgitation may be explained by differential regional strain resulting in mitral annular rotation. Copyright © 2016. Published by Elsevier Inc.

  19. Emergence of late-onset placental dysfunction: relationship to the change in uterine artery blood flow resistance between the first and third trimesters.

    Science.gov (United States)

    Llurba, Elisa; Turan, Ozhan; Kasdaglis, Tania; Harman, Chris R; Baschat, Ahmet A

    2013-06-01

    To test if emergence of third-trimester (T3) placental dysfunction is related to the impedance change in uterine artery blood flow resistance between the first trimester (T1) and T3. Mean T1 and T3 uterine artery (mUtA) pulsatility index (PI) was measured in 1098 singletons. Each patient's individual mUtA-PI change was calculated ([(T3 PI - T1 PI/interval in days)] × 100; ΔmUtA-PI). This parameter and T1 and T3 mUtA-PI z-scores were related to placenta-related disease (PRD) and to constitutionally small neonates (CS). Forty-seven (5%) women had PRD and 83 (8.7%) delivered a CS neonate. T1 and T3 mUtA-PI z-scores were higher with PRD (0.418 versus -0.097 and 1.06 versus -0.13, p Change in mUtA-PI (ΔmUtA PI) was similar for patients with PRD. However, the prevalence of PRD doubled with rising ΔmUtA-PI (11.1% versus 5.2%, p = 0.041). T3 uterine artery Doppler performs significantly better in detecting patients at risk for late-onset PRD than T1 or the gestational age change in uterine artery Doppler resistance This suggests that a proportion of late emerging PRD is not amenable to early screening by uterine artery Doppler. Further research is essential to identify the optimal screening strategy for late-onset placental dysfunction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  20. Pulmonary arterial hypertension : an update

    NARCIS (Netherlands)

    Hoendermis, E. S.

    2011-01-01

    Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance

  1. Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries

    Science.gov (United States)

    Bottrill, Fiona E; Douglas, Stephen A; Hiley, C Robin; White, Richard

    2000-01-01

    The possible role of the endothelium in modulating responses to human urotensin-II (U-II) was investigated using isolated segments of rat thoracic aorta, small mesenteric artery, left anterior descending coronary artery and basilar artery.Human U-II was a potent vasoconstrictor of endothelium-intact isolated rat thoracic aorta (EC50=3.5±1.1 nM, Rmax=103±10% of control contraction induced by 60 mM KCl and 1 μM noradrenaline). However the contractile response was not significantly altered by removal of the endothelium or inhibition of nitric oxide synthesis with L-NAME (100 μM). Human U-II did not cause relaxation of noradrenaline-precontracted, endothelium-intact rat aortae.Human U-II contracted endothelium-intact rat isolated left anterior descending coronary arteries (EC50=1.3±0.8 nM, Rmax=20.1±4.9% of control contraction induced by 10 μM 5-HT). The contractile response was significantly enhanced by removal of the endothelium (Rmax=55.4±16.1%). Moreover, human U-II caused concentration-dependent relaxation of 5-HT-precontracted arteries, which was abolished by L-NAME or removal of the endothelium.No contractile effects of human U-II were found in rat small mesenteric arteries. However the peptide caused potent, concentration- and endothelium-dependent relaxations of methoxamine-precontracted vessels. The relaxant responses were potentiated by L-NAME (300 μM) but abolished in the additional presence of 25 mM KCl (which inhibits the actions of endothelium-derived hyperpolarizing factor).The present study is the first to show that human U-II is a potent endothelium-dependent vasodilator in some rat resistance vessels, and acts through release of EDHF as well as nitric oxide. Our findings have also highlighted clear anatomical differences in the responses of different vascular beds to human U-II which are likely to be important in determining the overall cardiovascular activity of this peptide. PMID:10952676

  2. Contractile Force of Human Extraocular Muscle: A Theoretical Analysis

    Directory of Open Access Journals (Sweden)

    Hongmei Guo

    2016-01-01

    Full Text Available Aim. The length-contractile force relationships of six human extraocular muscles (EOMs in primary innervations should be determined during eye movement modeling and surgery of clinical EOMs. This study aims to investigate these relationships. Method. The proposal is based on the assumption that six EOMs have similar constitutive relationships, with the eye suspended in the primary position. The constitutive relationships of EOMs are obtained by optimizing from previous experimental data and the theory of mechanical equilibrium using traditional model. Further, simulate the existing experiment of resistance force, and then compare the simulated results with the existing experimental results. Finally, the mechanical constitutive relationships of EOMs are obtained. Results. The results show that the simulated resistance forces from the other four EOMs except for the horizontal recti well agree with previous experimental results. Conclusion. The mechanical constitutive relationships of six EOMs in primary innervations are obtained, and the rationality of the constitutive relationships is verified. Whereafter, the active stress-strain relationships of the six EOMs in the primary innervations are obtained. The research results can improve the eye movement model to predict the surgical amounts of EOMs before EOM surgery more precisely.

  3. Structure and function of cerebral and mesenteric resistance arteries in low-dose endotoxin-infused pregnant rats

    NARCIS (Netherlands)

    Wiegman, Marjon J; Van der Graaf, Anne Marijn; Henning, Robert H.; Zeeman, Gerda G.; Buikema, Hendrik; Faas, Marijke M.

    Objective: Since the cerebrovasculature likely plays a prominent role in the pathophysiology of eclampsia, we assessed the effects of low-dose endotoxin-induced experimental preeclampsia on the function and structure of rat posterior cerebral arteries (PCA) and mesenteric arteries (MA). Methods:

  4. Combined aerobic and resistance exercise training decreases peripheral but not central artery wall thickness in subjects with type 2 diabetes.

    NARCIS (Netherlands)

    Schreuder, T.H.A.; Munckhof, I.C.L. van den; Poelkens, F.; Hopman, M.T.; Thijssen, D.H.

    2015-01-01

    OBJECTIVE: Little is known about the impact of exercise training on conduit artery wall thickness in type 2 diabetes. We examined the local and systemic impact of exercise training on superficial femoral (SFA), brachial (BA), and carotid artery (CA) wall thickness in type 2 diabetes patients and

  5. Quantitative analysis of vasodilatory action of quercetin on intramural coronary resistance arteries of the rat in vitro.

    Directory of Open Access Journals (Sweden)

    Anna Monori-Kiss

    Full Text Available BACKGROUND: Dietary quercetin improves cardiovascular health, relaxes some vascular smooth muscle and has been demonstrated to serve as a substrate for the cyclooxygenase enzyme. AIMS: 1. To test quantitatively a potential direct vasodilatory effect on intramural coronary resistance artery segments, in different concentrations. 2. To scale vasorelaxation at different intraluminal pressure loads on such vessels of different size. 3. To test the potential role of prostanoids in vasodilatation induced by quercetin. METHODS: Coronary arterioles (70-240 µm were prepared from 24 rats and pressurized in PSS, using a pressure microangiometer. RESULTS: The spontaneous tone that developed at 50 mmHg was relaxed by quercetin in the 10(-9 moles/lit concentration (p<0.05, while 10(-5 moles/lit caused full relaxation. Significant relaxation was observed at all pressure levels (10-100 mmHg at 10(-7 moles/lit concentration of quercetin. The cyclooxygenase blocker indomethacin (10(-5 moles/lit induced no relaxation but contraction when physiological concentrations of quercetin were present in the tissue bath (p<0.02 with Anova, this contraction being more prominent in smaller vessels and in the higher pressure range (p<0.05, Pearson correlation. A further 2-8% contraction could be elicited by the NO blocker L-NAME (10(-4 moles/lit. CONCLUSION: These results demonstrate that circulating levels of quercetin (10(-7 moles/lit exhibit a substantial coronary vasodilatory effect. The extent of it is commeasurable with that of several other physiological mechanisms of coronary blood flow control. At least part of this relaxation is the result of an altered balance toward the production of endogenous vasodilatory prostanoids in the coronary arteriole wall.

  6. Resistance exercise training improves heart rate variability and muscle performance: a randomized controlled trial in coronary artery disease patients.

    Science.gov (United States)

    Caruso, F R; Arena, R; Phillips, S A; Bonjorno, J C; Mendes, R G; Arakelian, V M; Bassi, D; Nogi, C; Borghi-Silva, A

    2015-06-01

    Resistance exercise (RE) is an important part of cardiac rehabilitation. However, it is not known about the low intensity of RE training that could modify the heart rate variability (HRV), muscular strength and endurance in patients with coronary artery disease (CAD). To investigate the effects of high repetition/low load resistance training (HR/LL-RT) program on HRV and muscular strength and endurance in CAD patients. Randomized and controlled trial. Patients seen at the Cardiopulmonary Physical Therapy Laboratory between May 2011 and November 2013. Twenty male patients with CAD were randomized to a training group (61.3±5.2 years) or control group (61±4.4 years). 1 repetition maximum (1-RM) maneuver, discontinuous exercise test on the leg press (DET-L), and resting HRV were performed before and after 8 weeks of HR/LL-RT on a 45° leg press. RMSSD, SD1, mean HR and ApEn indices were calculated. The HR/LL-RT program consisted of a lower limb exercise using a 45° leg press; 3 sets of 20 repetitions, two times a week. The initial load was set at 30% of the 1-RM load and the duration of the HR/LL-RT program was performed for 8 weeks. After 8 weeks of HR/LL-RT there were significant increases of RMSSD and SD1 indices in the training group only (P<0.05). There was a significant decrease in mean HR after HR/LL-RT in the training group (P<0.05). There was a significantly higher ApEn after in the training group (P<0.05). There were significantly higher values in the training group in contrast to the control group (P<0.05). These results show positive improvements on HRV, as well as muscle strength and endurance in CAD patients. Eight weeks of HR/LL-RT is an effective sufficient to beneficially modify important outcomes as HRV, muscle strength and endurance in CAD patients.

  7. Dobutamine enhances both contractile function and energy reserves in hypoperfused canine right ventricle.

    Science.gov (United States)

    Yi, K D; Downey, H F; Bian, X; Fu, M; Mallet, R T

    2000-12-01

    Although the beta(1)-adrenergic agent dobutamine is used clinically to provide inotropic support to the failing myocardium, it could jeopardize the myocardium by depleting energy reserves. This investigation delineated the contractile and energetic effects of low versus high dobutamine doses in the hypoperfused right ventricular (RV) myocardium. The right coronary artery (RCA) of anesthetized dogs was cannulated for controlled perfusion with arterial blood, and regional RV contractile function was measured. RCA perfusion pressure was lowered from 100 mmHg baseline to 40 mmHg, and flow fell by 54%. At 15-min hypoperfusion, dobutamine was infused into the RCA at either 0.01 (low-dose dobutamine) or 0.06 microgram. kg(-1). min(-1) (high-dose dobutamine) for 15 min. Regional power (systolic segment shortening x isometric developed force x heart rate) stabilized at 63% of baseline during hypoperfusion. Low-dose dobutamine restored power to baseline but did not increase RV myocardial O(2) consumption (MVO(2)) and thus increased myocardial O(2) utilization efficiency (O(2)UE:power/MVO(2)). At 5 min, high-dose dobutamine enhancement of power was similar to that of low-dose dobutamine, but by 15 min, power and O(2)UE fell to untreated levels. Remarkably, low-dose dobutamine tripled cytosolic phosphorylation potential; in contrast, high-dose dobutamine lowered phosphorylation potential to 45% of the untreated value. Analyses of glucose uptake and glycolytic intermediates revealed sustained enhancement of glycolysis by low-dose dobutamine, but glycolysis became limited at glyceraldehyde 3-phosphate dehydrogenase during high-dose dobutamine treatment. In summary, low-dose dobutamine improved mechanical performance and efficiency of the hypoperfused RV myocardium while increasing myocardial energy reserves, but high-dose dobutamine failed to sustain improved function and depleted energy reserves. Dobutamine is capable of improving both contractile function and cellular

  8. Considerations for Contractile Electroactive Materials and Actuators

    Energy Technology Data Exchange (ETDEWEB)

    Lenore Rasmussen, David Schramm, Paul Rasmussen, Kevin Mullaly, Ras Labs, LLC, Intelligent Materials for Prosthetics & Automation, Lewis D. Meixler, Daniel Pearlman and Alice Kirk

    2011-05-23

    Ras Labs produces contractile electroactive polymer (EAP) based materials and actuators that bend, swell, ripple, and contract (new development) with low electric input. In addition, Ras Labs produces EAP materials that quickly contract and expand, repeatedly, by reversing the polarity of the electric input, which can be cycled. This phenomenon was explored using molecular modeling, followed by experimentation. Applied voltage step functions were also investigated. High voltage steps followed by low voltage steps produced a larger contraction followed by a smaller contraction. Actuator control by simply adjusting the electric input is extremely useful for biomimetic applications. Muscles are able to partially contract. If muscles could only completely contract, nobody could hold an egg, for example, without breaking it. A combination of high and low voltage step functions could produce gross motor function and fine manipulation within the same actuator unit. Plasma treated electrodes with various geometries were investigated as a means of providing for more durable actuation.

  9. Genome sequence of Haloplasma contractile, an unusual contractile bacterium from a deep-sea anoxic brine lake.

    KAUST Repository

    Antunes, Andre

    2011-09-01

    We present the draft genome of Haloplasma contractile, isolated from a deep-sea brine and representing a new order between Firmicutes and Mollicutes. Its complex morphology with contractile protrusions might be strongly influenced by the presence of seven MreB/Mbl homologs, which appears to be the highest copy number ever reported.

  10. Resveratrol Increases Serum BDNF Concentrations and Reduces Vascular Smooth Muscle Cells Contractility via a NOS-3-Independent Mechanism

    Directory of Open Access Journals (Sweden)

    Michał Wiciński

    2017-01-01

    Full Text Available Resveratrol is a polyphenol that presents both antineuroinflammatory properties and the ability to interact with NOS-3, what contributes to vasorelaxation. Brain-derived neurotrophic factor (BNDF, a molecule associated with neuroprotection in many neurodegenerative disorders, is considered as an important element of maintaining stable cerebral blood flow. Vascular smooth muscle cells (VSMCs are considered to be an important element in the pathogenesis of neurodegeneration and a potential preventative target by agents which reduce the contractility of the vessels. Our main objectives were to define the relationship between serum and long-term oral resveratrol administration in the rat model, as well as to assess the effect of resveratrol on phenylephrine- (PHE- induced contraction of vascular smooth muscle cells (VSMCs. Moreover, we attempt to define the dependence of contraction mechanisms on endothelial NO synthase. Experiments were performed on Wistar rats (n=17 pretreated with resveratrol (4 weeks; 10 mg/kg p.o. or placebo. Serum BDNF levels were quantified after 2 and 4 weeks of treatment with ELISA. Contraction force was measured on isolated and perfused tail arteries as the increase of perfusion pressure with a constant flow. Values of serum BNDF in week 0 were 1.18±0.12 ng/mL (treated and 1.17±0.13 ng/mL (control (p = ns. After 2 weeks of treatment, BDNF in the treatment group was higher than in controls, 1.52±0.23 ng/mL and 1.24±0.13 ng/mL, respectively. (p=0.02 Following 4 weeks of treatment, BDNF values were higher in the resveratrol group compared to control 1.64±0.31 ng/mL and 1.32±0.26 ng/mL, respectively (p=0.031. EC50 values obtained for PHE in resveratrol pretreated arteries were significantly higher than controls (5.33±1.7 × 10−7 M/L versus 4.53±1.2 × 10−8 M/L, p<0.05. These results show a significant increase in BDNF concentration in the resveratrol pretreated group. The reactivity of resistant

  11. Relationship between resistant hypertension and arterial stiffness assessed by brachial-ankle pulse wave velocity in the older patient

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    Chung CM

    2014-09-01

    Full Text Available Chang-Min Chung,1,2 Hui-Wen Cheng,2 Jung-Jung Chang,2 Yu-Sheng Lin,2 Ju-Feng Hsiao,2 Shih-Tai Chang,1 Jen-Te Hsu2,31School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, 2Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, 3Department of Medicine, College of Medicine, Chang Gung University, Taoyuan County, TaiwanBackground: Resistant hypertension (RH is a common clinical condition associated with increased cardiovascular mortality and morbidity in older patients. Several factors and conditions interfering with blood pressure (BP control, such as excess sodium intake, obesity, diabetes, older age, kidney disease, and certain identifiable causes of hypertension are common in patients resistant to antihypertensive treatment. Arterial stiffness, measured by brachial-ankle pulse wave velocity (baPWV, is increasingly recognized as an important prognostic index and potential therapeutic target in hypertensive patients. The aim of this study was to determine whether there is an association between RH and arterial stiffness. Methods: This study included 1,620 patients aged ≥65 years who were referred or self-referred to the outpatient hypertension unit located at a single cardiovascular center. They were separated into normotensive, controlled BP, and resistant hypertension groups. Home BP, blood laboratory parameters, echocardiographic studies and baPWV all were measured. Results: The likelihood of diabetes mellitus was significantly greater in the RH group than in the group with controlled BP (odds ratio 2.114, 95% confidence interval [CI] 1.194–3.744, P=0.010. Systolic BP was correlated in the RH group significantly more than in the group with controlled BP (odds ratio 1.032, 95% CI 1.012–1.053, P=0.001. baPWV (odds ratio 1.084, 95% CI 1.016–1.156, P=0.015 was significantly correlated with the presence of RH. The other factors were negatively correlated with the existence of RH.Conclusion: In

  12. Inactivation of serum response factor contributes to decrease vascular muscular tone and arterial stiffness in mice.

    Science.gov (United States)

    Galmiche, Guillaume; Labat, Carlos; Mericskay, Mathias; Aissa, Karima Ait; Blanc, Jocelyne; Retailleau, Kevin; Bourhim, Mustapha; Coletti, Dario; Loufrani, Laurent; Gao-Li, Jacqueline; Feil, Robert; Challande, Pascal; Henrion, Daniel; Decaux, Jean-François; Regnault, Véronique; Lacolley, Patrick; Li, Zhenlin

    2013-03-29

    Vascular smooth muscle (SM) cell phenotypic modulation plays an important role in arterial stiffening associated with aging. Serum response factor (SRF) is a major transcription factor regulating SM genes involved in maintenance of the contractile state of vascular SM cells. We investigated whether SRF and its target genes regulate intrinsic SM tone and thereby arterial stiffness. The SRF gene was inactivated SM-specific knockout of SRF (SRF(SMKO)) specifically in vascular SM cells by injection of tamoxifen into adult transgenic mice. Fifteen days later, arterial pressure and carotid thickness were lower in SRF(SMKO) than in control mice. The carotid distensibility/pressure and elastic modulus/wall stress curves showed a greater arterial elasticity in SRF(SMKO) without modification in collagen/elastin ratio. In SRF(SMKO), vasodilation was decreased in aorta and carotid arteries, whereas a decrease in contractile response was found in mesenteric arteries. By contrast, in mice with inducible SRF overexpression, the in vitro contractile response was significantly increased in all arteries. Without endothelium, the contraction was reduced in SRF(SMKO) compared with control aortic rings owing to impairment of the NO pathway. Contractile components (SM-actin and myosin light chain), regulators of the contractile response (myosin light chain kinase, myosin phosphatase target subunit 1, and protein kinase C-potentiated myosin phosphatase inhibitor) and integrins were reduced in SRF(SMKO). SRF controls vasoconstriction in mesenteric arteries via vascular SM cell phenotypic modulation linked to changes in contractile protein gene expression. SRF-related decreases in vasomotor tone and cell-matrix attachment increase arterial elasticity in large arteries.

  13. Pro-contractile action of the Na,K-ATPase/Src-kinase signaling pathway in the vascular wall

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Aalkjær, Christian; Matchkov, Vladimir

    Aim: Na,K-ATPase is essential for maintaining the transmembrane ion gradient and might initiate various intracellular signaling. These signals possibly act through a modification of the local ion concentrations or via Src-kinase activation. It is known that inhibition of the α-2 isoform of Na...... of ouabain. Here we demonstrate results of our research on the mechanisms involved in the modulation of vascular wall contractility by ouabain-sensitive Na,K-ATPase. Methods: The experiments were performed using rat mesenteric arteries in isometric myograph conditions. To inhibit kinase activity a Src......-family selective tyrosine kinase inhibitor, PP2, and pNaKtide - a membrane-permeable small peptide which antagonizes ouabain-induced activation of Src-kinase were used. Results: The pro-contractile action of ouabain is associated with activation of Src. This is supported by Western blot analyses showing activation...

  14. Cardiac contractile function during coronary stenosis in dogs: association of adenosine in glycolytic dependence.

    Science.gov (United States)

    Fang, H K; Sturgeon, C; Segil, L J; Ripper, R L; Law, W R

    1997-05-01

    We tested the hypothesis that during critical coronary stenosis, endogenous adenosine alters myocardial glucose utilization to support myocardial contractile function (MCF). Anesthetized mongrel dogs were instrumented to measure hemodynamic variables, regional MCF (sonomicrometry), and substrate uptakes. Critical coronary artery stenosis was established with a screw clamp on the left circumflex coronary artery (LCX). Either 8-phenyltheophylline (3 x 10(-7) mol/min; adenosine-receptor blockade), iodoacetate (1 x 10(-5) mol/min; glycolysis blockade), or vehicle was infused into the LCX and the left anterior descending coronary artery (LAD). Critical coronary stenosis caused small decreases in arterial blood pressure and LCX blood flow, but no significant changes in MCF or other hemodynamics. There was a significant decrease in the O2 supply-to-consumption ratio in the stenotic region and an increased glucose uptake. Infusion of either 8-phenyltheophylline or iodoacetate caused a decrease in MCF in the stenotic LCX region concomitant with a decreased glucose uptake and without further changes in blood flow. This was not seen in the nonstenotic (LAD) region. These data support the hypothesis, indicating that glycolysis is vital for maintaining regional MCF during a decrease in the myocardial O2 supply-to-consumption ratio and that adenosine is important in this regard, independent of its vasoactive properties.

  15. Effect of beta-adrenergic blockade on elevated arterial compliance and low systemic vascular resistance in cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Bendtsen, F; Henriksen, Jens Henrik Sahl

    2001-01-01

    ) of 17.8 mmHg, and responded to beta-blocker treatment with a significant reduction in the HVPG (-16%; P beta-adrenergic blockade (1.27 versus 1.29 ml/mmHg, +2%, ns), whereas...... with beta-blockers, but the effect of this treatment on arterial compliance has not been investigated. The aim of the present study was therefore to assess the effects of propranolol on the arterial compliance of patients with cirrhosis. METHODS: Twenty patients with cirrhosis underwent a haemodynamic...... with beta-blockers increases small vessel (arteriolar) vascular tone towards the normal level, but does not affect the elevated compliance of the larger arteries in patients with cirrhosis....

  16. Effect of beta-adrenergic blockade on elevated arterial compliance and low systemic vascular resistance in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Bendtsen, Flemming; Henriksen, Jens Henrik

    2001-01-01

    investigation with determination of splanchnic and systemic haemodynamics. Arterial compliance was determined as the ratio of the stroke volume to the pulse pressure and compared to normal values. RESULTS: All the patients had significant portal hypertension, with a mean hepatic venous pressure gradient (HVPG......) of 17.8 mmHg, and responded to beta-blocker treatment with a significant reduction in the HVPG (-16%; P elevated (1.27 versus controls 1.01 ml/mmHg; P ... with beta-blockers increases small vessel (arteriolar) vascular tone towards the normal level, but does not affect the elevated compliance of the larger arteries in patients with cirrhosis....

  17. Considerations for Contractile Electroactive Materials and Actuators

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Lenore; Erickson, Carl J.; Meixler, Lewis D.; Ascione, George; Gentile, Charles A.; Tilson, Carl; Bernasek, Stephen L.; Abelev, Esta

    2010-02-19

    Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface.

  18. Efeitos do treinamento resistido sobre a pressão arterial de idosos Efectos del entrenamiento de resistencia sobre la presión arterial de añosos Effects of resistance training on blood pressure in the elderly

    Directory of Open Access Journals (Sweden)

    Andréia Cristiane Carrenho Queiroz

    2010-07-01

    Full Text Available O processo de envelhecimento reduz drasticamente a massa, a força e a potência musculares, diminuindo a capacidade de execução das atividades da vida diária. A prática de exercícios resistidos pode reverter esse quadro, auxiliando na manutenção da massa muscular e melhorando sua força e resistência. No entanto, o envelhecimento ocasiona alterações cardiovasculares, que podem resultar em aumento nos níveis de pressão arterial de repouso, sendo importante analisar os efeitos do exercício resistido sobre a pressão arterial de indivíduos idosos. O objetivo deste estudo é avaliar o conhecimento científico existente sobre as respostas da pressão arterial aos exercícios resistidos e seus mecanismos em idosos. Para tanto, realizou-se uma revisão bibliográfica baseada nas literaturas portuguesa e inglesa relacionadas ao tema. Com base nos estudos encontrados, o corpus atual, embora escasso e controverso, sugere que, de forma crônica, os exercícios resistidos podem ter efeito hipotensor em indivíduos idosos. Entretanto, esse efeito ocorre, principalmente, em idosos normotensos e com o treinamento de baixa intensidade. Os mecanismos envolvidos nessa resposta hipotensora ainda precisam ser elucidados. Embora o treinamento resistido esteja sendo recomendado para idosos e haja alguns indicativos de que ele possa ter efeito hipotensor crônico, ainda há carência de dados científicos e muitas controvérsias sobre o assunto, o que evidencia que este ainda é um campo aberto à investigação.El proceso de envejecimiento reduce drásticamente la masa, la fuerza y la potencia muscular, disminuyendo la capacidad de ejecución de las actividades de la vida diaria. La práctica de ejercicios de resistencia puede revertir ese cuadro, auxiliando en la manutención de la masa muscular y mejorando su fuerza y resistencia. Mientras tanto, el envejecimiento ocasiona alteraciones cardiovasculares, que pueden resultar en aumento en los niveles

  19. Geometrical Origins of Contractility in Disordered Actomyosin Networks

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    Martin Lenz

    2014-10-01

    Full Text Available Movement within eukaryotic cells largely originates from localized forces exerted by myosin motors on scaffolds of actin filaments. Although individual motors locally exert both contractile and extensile forces, large actomyosin structures at the cellular scale are overwhelmingly contractile, suggesting that the scaffold serves to favor contraction over extension. While this mechanism is well understood in highly organized striated muscle, its origin in disordered networks such as the cell cortex is unknown. Here, we develop a mathematical model of the actin scaffold’s local two- or three-dimensional mechanics and identify four competing contraction mechanisms. We predict that one mechanism dominates, whereby local deformations of the actin break the balance between contraction and extension. In this mechanism, contractile forces result mostly from motors plucking the filaments transversely rather than buckling them longitudinally. These findings shed light on recent in vitro experiments and provide a new geometrical understanding of contractility in the myriad of disordered actomyosin systems found in vivo.

  20. [Effects of aerobic exercise combined with resistance training on the cardiorespiratory fitness and exercise capacity of patients with stable coronary artery disease].

    Science.gov (United States)

    Liu, S X; Chen, Y Y; Xie, K L; Zhang, W L

    2017-12-24

    Objective: To observe the effects of aerobic exercise combined with resistance training on the cardiorespiratory fitness and exercise capacity of patients with stable coronary artery disease (CAD) . Methods: From June 2014 to December 2015, 73 patients with stable CAD in our department were recruited and randomly assigned to two groups: the control group ( n= 38) and the exercise group ( n= 35) . Patients in both groups received conventional medical treatment for CAD and related cardiac health education. While for patients in exercise group, a twelve-week aerobic exercise combined with resistance training program were applied on top of conventional treatment and health education. Cardiorespiratory fitness and exercise capacity were evaluated by cardiopulmonary exercise testing. Results: (1) The exercise capacity was significantly increased in the exercise group after 12 weeks training as compared to baseline level: peak oxygen uptake per kilogram ( (26.25±5.14) ml·kg(-1)·min(-1) vs. (20.88±4.59) ml·kg(-1)·min(-1)) , anaerobic threshold ( (15.24±2.75) ml·kg(-1)·min(-1) vs. (13.52±2.92) ml·kg(-1)·min(-1)], peak oxygen pulse ( (11.91±2.89) ml/beat vs. (9.77±2.49) ml/beat) , peak Watts ( (113.2±34.0) W vs. (103.7±27.9) W) , peak metabolic equivalent ( (7.57±1.46) METs vs. (6.00±1.32) METs) (all Pexercise group than in control group (all Pcoronary artery disease. This combined exercise program can significantly improve the cardiorespiratory fitness and exercise capacity of patients with stable coronary artery disease.

  1. Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR

    DEFF Research Database (Denmark)

    Lemkens, Pieter; Spijkers, Leon Ja; Meens, Merlijn J

    2017-01-01

    Endothelin 1 (ET-1), a potent vasoconstrictor, pro-mitogenic and pro-inflammatory peptide, may promote development of endothelial dysfunction and arterial remodeling. ET-1 can be formed through cleavage of big-ET-1 by endothelin-converting enzyme (ECE) or neutral endopeptidase (NEP). We investiga...

  2. Dopplerfluxometria das artérias renais: valores normais das velocidades sistólica e diastólica e do índice resistivo nas artérias renais principais Renal arteries Dopplerfluxometry: normal systolic and diastolic flow velocities and resistive index values in the main renal arteries

    Directory of Open Access Journals (Sweden)

    M.B. Melo

    2006-08-01

    Full Text Available Dopplerfluxometry of renal arteries has been used to estimate renal perfusion in humans. The aim of this study was to use Dopplerfluxometry technique to calculate the resistive index of main renal arteries in dogs, measuring their systolic and diastolic blood flow velocities. Twenty (10 males, 10 females, adult mongrel dogs, were used in this study. The dogs were submitted to Doppler sonographic evaluation of left and right main renal arteries. The systolic and diastolic blood flow velocities, expressed (in centimeters per second as mean and standard deviation were 79.96± 8.82 and 28.86± 5.11 in the right main renal artery and 80.22± 6.99 and 29.62± 4.14 in the left main renal artery. The value of resistive index expressed as mean ± standard deviation was 0.64± 0.04 for the right main renal artery and 0.63± 0.028 in the left main renal artery.

  3. Update on corpus cavernosum smooth muscle contractile pathways in erectile function: a role for testosterone?

    Science.gov (United States)

    Zhang, Xin-Hua; Melman, Arnold; Disanto, Michael E

    2011-07-01

    Normal erectile function (EF) involves a coordinated relaxation of the arteries that supply the penis and the corpus cavernosum smooth muscle (CCSM), resulting in expansion of the sinusoids and increased intracavernous pressure. But the CCSM spends the majority of its time in the contracted state which is mediated by norepinephrine released from nerve endings and other vasoconstrictors like endothelins released from the endothelium. These agents cause smooth muscle myosin (SMM) phosphorylation by elevating intracellular calcium. When calcium returns to basal levels, the calcium sensitivity increases and prevents myosin dephosphorylation, which involves the RhoA/Rho-kinase (ROK) mechanism, thus maintaining force. Although mounting evidences demonstrate that androgens have a major influence on EF that is not just centrally mediated, this notion remains quite controversial. To summarize the current knowledge on CCSM contractile pathways, the role they play in modulating EF, and the influence of androgens. The article reviews the literature and contains some previously unpublished data on CCSM contraction signaling including the role that androgens are known to play in modulating these pathways. Data from peer-reviewed publications and previously unpublished observations. In addition to downregulation of many pro-erectile molecular mechanisms, decreased testosterone (T) levels upregulate CCSM contractility, including hyperresponsiveness to α-adrenergic agonists, increased SMM phosphorylation, alteration of SMM isoform composition, activation of RhoA/ROK signaling and modulation of sphingosine-1-phosphate regulation of CCSM tone. Decreased T levels upregulate CCSM contractile signaling. Meanwhile, it downregulates CCSM relaxation pathways synergizing to produce erectile dysfunction (ED). Although some urologists and researchers are still skeptical of the influence of androgens on penile erection, understanding these molecular control mechanisms as well as the influence

  4. Contractility-afterload mismatch in patients with protein-losing enteropathy after the Fontan operation.

    Science.gov (United States)

    Ozawa, Hideto; Ueno, Takayoshi; Iwai, Shigemitsu; Kawata, Hiroaki; Nishigaki, Kyouichi; Kishimoto, Hidefumi; Sawa, Yoshiki

    2014-10-01

    This study aimed to clarify the relationship between onset of protein-losing enteropathy (PLE) and Fontan circulation, with special reference to the development of contractility-afterload mismatch. The PLE group comprised 9 patients who experienced PLE after undergoing the Fontan operation, and the control group consisted of 32 patients had did not experienced PLE more than 10 years after the Fontan operation. The study compared the pre- and postoperative values of arterial elastance (Ea), end-systolic elastance (Ees), and contractility-afterload mismatch (Ea/Ees). Furthermore, the variations in the values were examined during the preoperative, postoperative, and midterm postoperative periods in seven PLE patients who underwent cardiac catheterization at the onset of PLE and during the pre- and postintervention periods in three PLE patients who underwent surgical intervention to improve the Fontan circulation after the onset of PLE. Comparison of the values obtained before and after Fontan operations showed that the Ea values increased significantly in the PLE group. However, the pre- and postoperative Ees values did not differ in the two groups. During the postoperative period, Ea/Ees increased significantly, and the Ea and Ea/Ees values increased continuously until the onset of PLE in the PLE group. In the patients who underwent surgical intervention to improve the Fontan circulation after the onset of PLE, the Ea/Ees decreased significantly, and the serum albumin levels improved after the intervention. Contractility-afterload mismatch, mainly caused by the increase in the afterload of the systemic ventricle, may have an important role in the development of PLE after the Fontan operation.

  5. Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries

    DEFF Research Database (Denmark)

    Ahnstedt, Hilda; Cao, Lei; Krause, Diana N

    2013-01-01

    Male-female differences may significantly impact stroke prevention and treatment in men and women, however underlying mechanisms for sexual dimorphism in stroke are not understood. We previously found in males that cerebral ischemia upregulates contractile receptors in cerebral arteries, which...... is associated with lower blood flow. The present study investigates if cerebral arteries from men and women differ in cerebrovascular receptor upregulation....

  6. Regulator of calcineurin 1 modulates vascular contractility and stiffness through the upregulation of COX-2-derived prostanoids.

    Science.gov (United States)

    García-Redondo, Ana B; Esteban, Vanesa; Briones, Ana M; Díaz Del Campo, Lucía S; González-Amor, María; Méndez-Barbero, Nerea; Campanero, Miguel R; Redondo, Juan M; Salaices, Mercedes

    2018-01-05

    Cyclooxygenase-2 (COX-2) derived-prostanoids participate in the altered vascular function and mechanical properties in cardiovascular diseases. We investigated whether regulator of calcineurin 1 (Rcan1) participates in vascular contractility and stiffness through the regulation of COX-2. For this, wild type (Rcan1 +/+ ) and Rcan1-deficient (Rcan1 -/- ) mice untreated or treated with the COX-2 inhibitor rofecoxib were used. Vascular function and structure were analysed by myography. COX-2 and phospo-p65 expression were studied by western blotting and immunohistochemistry and TXA 2 production by ELISA. We found that Rcan1 deficiency increases COX-2 and IL-6 expression and NF-κB activation in arteries and vascular smooth muscle cells (VSMC). Adenoviral-mediated re-expression of Rcan1.4 in Rcan1 -/- VSMC normalized COX-2 expression. Phenylephrine-induced vasoconstrictor responses were greater in aorta from Rcan1 -/- compared to Rcan1 +/+ mice. This increased response were diminished by etoricoxib, furegrelate, SQ 29548, cyclosporine A and parthenolide, inhibitors of COX-2, TXA 2 synthase, TP receptors, calcineurin and NF-κB, respectively. Endothelial removal and NOS inhibition increased phenylephrine responses only in Rcan1 +/+ mice. TXA 2 levels were greater in Rcan1 -/- mice. In small mesenteric arteries, vascular function and structure were similar in both groups of mice; however, vessels from Rcan1 -/- mice displayed an increase in vascular stiffness that was diminished by rofecoxib. In conclusion, our results suggest that Rcan1 might act as endogenous negative modulator of COX-2 expression and activity by inhibiting calcineurin and NF-kB pathways to maintain normal contractility and vascular stiffness in aorta and small mesenteric arteries, respectively. Our results uncover a new role for Rcan1 in vascular contractility and mechanical properties. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. PC-PLC/sphingomyelin synthase activity plays a central role in the development of myogenic tone in murine resistance arteries.

    Science.gov (United States)

    Mauban, Joseph R H; Zacharia, Joseph; Fairfax, Seth; Wier, Withrow Gil

    2015-06-15

    Myogenic tone is an intrinsic property of the vasculature that contributes to blood pressure control and tissue perfusion. Earlier investigations assigned a key role in myogenic tone to phospholipase C (PLC) and its products, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Here, we used the PLC inhibitor, U-73122, and two other, specific inhibitors of PLC subtypes (PI-PLC and PC-PLC) to delineate the role of PLC in myogenic tone of pressurized murine mesenteric arteries. U-73122 inhibited depolarization-induced contractions (high external K(+) concentration), thus confirming reports of nonspecific actions of U-73122 and its limited utility for studies of myogenic tone. Edelfosine, a specific inhibitor of PI-PLC, did not affect depolarization-induced contractions but modulated myogenic tone. Because PI-PLC produces IP3, we investigated the effect of blocking IP3 receptor-mediated Ca(2+) release on myogenic tone. Incubation of arteries with xestospongin C did not affect tone, consistent with the virtual absence of Ca(2+) waves in arteries with myogenic tone. D-609, an inhibitor of PC-PLC and sphingomyelin synthase, strongly inhibited myogenic tone and had no effect on depolarization-induced contraction. D-609 appeared to act by lowering cytoplasmic Ca(2+) concentration to levels below those that activate contraction. Importantly, incubation of pressurized arteries with a membrane-permeable analog of DAG induced vasoconstriction. The results therefore mandate a reexamination of the signaling pathways activated by the Bayliss mechanism. Our results suggest that PI-PLC and IP3 are not required in maintaining myogenic tone, but DAG, produced by PC-PLC and/or SM synthase, is likely through multiple mechanisms to increase Ca(2+) entry and promote vasoconstriction. Copyright © 2015 the American Physiological Society.

  8. Effects of exercise training on coronary collateralization and control of collateral resistance

    Science.gov (United States)

    Parker, Janet L.

    2011-01-01

    Coronary collateral vessels serve as a natural protective mechanism to provide coronary flow to ischemic myocardium secondary to critical coronary artery stenosis. The innate collateral circulation of the normal human heart is typically minimal and considerable variability occurs in extent of collateralization in coronary artery disease patients. A well-developed collateral circulation has been documented to exert protective effects upon myocardial perfusion, contractile function, infarct size, and electrocardiographic abnormalities. Thus therapeutic augmentation of collateral vessel development and/or functional adaptations in collateral and collateral-dependent arteries to reduce resistance into the ischemic myocardium represent a desirable goal in the management of coronary artery disease. Tremendous evidence has provided documentation for the therapeutic benefits of exercise training programs in patients with coronary artery disease (and collateralization); mechanisms that underlie these benefits are numerous and multifaceted, and currently under investigation in multiple laboratories worldwide. The role of enhanced collateralization as a major beneficial contributor has not been fully resolved. This topical review highlights literature that examines the effects of exercise training on collateralization in the diseased heart, as well as effects of exercise training on vascular endothelial and smooth muscle control of regional coronary tone in the collateralized heart. Future directions for research in this area involve further delineation of cellular/molecular mechanisms involved in effects of exercise training on collateralized myocardium, as well as development of novel therapies based on emerging concepts regarding exercise training and coronary artery disease. PMID:21565987

  9. Actual vs optimal fetal hematocrit measured with punctures of cord blood in utero: Relationship with umbilical artery resistance.

    Science.gov (United States)

    Brun, Jean-Frédéric; Boulot, Pierre; Varlet-Marie, Emmanuelle

    2016-01-01

    Physiological studies on fetal blood in narrow glass tubes have suggested that fetal optimal hematocrit (hct) might be as high as 60%. A theoretical 'ideal' hct can also be predicted with a theoretical curve of hematocrit/viscosity (h/η) ratio vs hct constructed with Quemada's model. We used the database of one of our previous papers on fetal hemorheology to reinterpret its results with this concept. A series of 28 intrauterine cord punctures (between 19 and 33 weeks gestation) with doppler measurements of resistance in umbilical arteries was studied. The theoretical 'optimal hematocrit' was well correlated to actual (r = 0.857, p hematocrit (r = 0.407, p hematocrit, suggesting that the discrepancy between ideal and actual may reflect an adaptative decrease aiming at reducing vascular resistance. These findings indicate that prediction of ideal hematocrit with Quemada's equation makes sense in fetal blood, and suggest that a 'viscoregulatory mechanism' maintains hematocrit below this theoretical value in order to avoid excess vascular resistance.

  10. Growth Hormone, Insulin-Like Growth Factor-1, Insulin Resistance, and Leukocyte Telomere Length as Determinants of Arterial Aging in Subjects Free of Cardiovascular Diseases.

    Science.gov (United States)

    Strazhesko, Irina D; Tkacheva, Olga N; Akasheva, Dariga U; Dudinskaya, Ekaterina N; Plokhova, Ekaterina V; Pykhtina, Valentina S; Kruglikova, Anna S; Brailova, Natalia V; Sharashkina, Natalia V; Kashtanova, Daria A; Isaykina, Olesya Y; Pokrovskaya, Mariya S; Vygodin, Vladimir A; Ozerova, Irina N; Skvortsov, Dmitry A; Boytsov, Sergey A

    2017-01-01

    Background: Increased arterial stiffness (AS), intima-media thickness (IMT), and the presence of atherosclerotic plaques (PP) have been considered as important aspects of vascular aging. It is well documented that the cardiovascular system is an important target organ for growth hormone (GH) and insulin-like growth factor (IGF)-1 in humans, and GH /IGF-1 deficiency significantly increases the risk for cardiovascular diseases (CVD). The telomere length of peripheral blood leukocytes (LTL) is a biomarker of cellular senescence and that has been proposed as an independent predictor of (CVD). The aim of this study is to determine the role of GH/IGF-1, LTL and their interaction cardiovascular risk factors (CVRF) in the vascular aging. Methods: The study group included 303 ambulatory participants free of known CVD (104 males and 199 females) with a mean age of 51.8 ± 13.3 years. All subjects had one or more CVRF [age, smoking, arterial hypertension, obesity, dyslipidemia, fasting hyperglycemia, insulin resistance-HOMA (homeostatic model assessment) >2.5, or high glycated hemoglobin]. The study sample was divided into the two groups according to age as "younger" ( m ≤ 45 years, f ≤ 55 years) and "older" ( m > 45 years, f > 55 years). IMT and PP were determined by ultrasonography, AS was determined by measuring the carotid-femoral pulse wave velocity (c-f PWV) using the SphygmoCor system (AtCor Medical). LTL was determined by PCR. Serum IGF-1 and GH concentrations we measured by immunochemiluminescence analysis. Results: Multiple linear regression analysis with adjustment for CVRF indicated that HOMA, GH, IGF-1, and LTL had an independent relationship with all the arterial wall parameters investigated in the younger group. In the model with c-f PWV as a dependent variable, p aging in younger healthy participants.

  11. Actin in dividing cells: contractile ring filaments bind heavy meromyosin.

    Science.gov (United States)

    Schroeder, T E

    1973-06-01

    Many microfilaments and microtubules are well preserved after glycerol-extraction of HeLa cells at room temperature (22 degrees ). Incubation in heavy meromyosin from rabbit skeletal muscle results in conspicuous and characteristic "decoration" of microfilaments of the contractile ring. Decoration is completely prevented by 10 mM ATP or 2 mM pyrophosphate, and fails to occur if heavy meromyosin is either omitted or replaced by egg albumin, a nonspecific protein. Decorated microfilaments have a substructure consisting of polarized, repeating arrowheads 27-35 nm apart. The specificity of these results strongly suggests that microfilaments of the contractile ring in HeLa cells are closely related to muscle actin. Very thin undecorated strands among the microfilaments of the contractile ring possibly represent a myosin component. These findings are discussed in terms of: the actomyosin-like properties of the contractile ring as a mechanochemical organelle that causes cell cleavage; the probable universal occurrence of actin-like protein in all dividing animal cells; and the contractile ring's combined sensitivity to cytochalasin B and its affinity for heavy meromyosin, a combination unique among microfilamentous organelles.

  12. Energy harvesting from arterial blood pressure for powering embedded micro sensors in human brain

    Science.gov (United States)

    Nanda, Aditya; Karami, M. Amin

    2017-03-01

    This manuscript investigates energy harvesting from arterial blood pressure via the piezoelectric effect for the purpose of powering embedded micro-sensors in the human brain. One of the major hurdles in recording and measuring electrical data in the human nervous system is the lack of implantable and long term interfaces that record neural activity for extended periods of time. Recently, some authors have proposed micro sensors implanted deep in the brain that measure local electrical and physiological data which are then communicated to an external interrogator. This paper proposes a way of powering such interfaces. The geometry of the proposed harvester consists of a piezoelectric, circular, curved bimorph that fits into the blood vessel (specifically, the Carotid artery) and undergoes bending motion because of blood pressure variation. In addition, the harvester thickness is constrained such that it does not modify arterial wall dynamics. This transforms the problem into a known strain problem and the integral form of Gauss's law is used to obtain an equation relating arterial wall motion to the induced voltage. The theoretical model is validated by means of a Multiphysics 3D-FEA simulation comparing the harvested power at different load resistances. The peak harvested power achieved for the Carotid artery (proximal to Brain), with PZT-5H, was 11.7 μW. The peak power for the Aorta was 203.4 μW. Further, the variation of harvested power with variation in the harvester width and thickness, arterial contractility, and pulse rate is investigated. Moreover, potential application of the harvester as a chronic, implantable and real-time Blood pressure sensor is considered. Energy harvested via this mechanism will also have applications in long-term, implantable Brain Micro-stimulation.

  13. Effect of serotonin on small intestinal contractility in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, M.B.; Arif, F.; Gregersen, H.

    2008-01-01

    -duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase In frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile...

  14. Contractile injection systems of bacteriophages and related systems

    DEFF Research Database (Denmark)

    Taylor, Nicholas M I; van Raaij, Mark J; Leiman, Petr G

    2018-01-01

    through the target cell membrane. Subsequently, the bacteriophage genome is injected through the tube. The structural transformation of the bacteriophage T4 baseplate upon binding to the host cell has been recently described in near-atomic detail. In this review we discuss structural elements and features...... of this mechanism that are likely to be conserved in all contractile injection systems (systems evolutionary and structurally related to contractile bacteriophage tails). These include the type VI secretion system (T6SS), which is used by bacteria to transfer effectors into other bacteria and into eukaryotic cells...

  15. Comparison of contractile and extensile pneumatic artificial muscles

    Science.gov (United States)

    Pillsbury, Thomas E.; Wereley, Norman M.; Guan, Qinghua

    2017-09-01

    Pneumatic artificial muscles (PAMs) are used in robotic and prosthetic applications due to their high power to weight ratio, controllable compliance, and simple design. Contractile PAMs are typically used in traditional hard robotics in place of heavy electric motors. As the field of soft robotics grows, extensile PAMs are beginning to have increased usage. This work experimentally tests, models, and compares contractile and extensile PAMs to demonstrate the advantages and disadvantages of each type of PAM and applications for which they are best suited.

  16. Differential vasoactive effects of sildenafil and tadalafil on cerebral arteries

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Gupta, Saurabh; Nilsson, Elisabeth

    2012-01-01

    in vitro and on middle meningeal arteries in vivo. By Western blot PDE5 was detected in both cerebral and meningeal arteries, though with minor variations in band intensity between vascular beds. Rat middle cerebral artery diameter was investigated using pressurised arteriography, applying UK-114......,542, sildenafil, and tadalafil intra- or extra-luminally. Effects on the dural middle meningeal artery were studied in the in vivo closed cranial window model. At high concentrations, abluminal sildenafil and UK-114,542, but not tadalafil, induced dilatation of the middle cerebral artery. Luminal application....... In conclusion, PDE5 inhibitors applied luminally had minor contractile effect, whereas abluminal sildenafil induced middle cerebral artery dilatation above therapeutic levels. In vivo, sildenafil dilated middle meningeal artery concomitant with a reduction in blood pressure. Tadalafil had no dilatory effects...

  17. Constriction of collateral arteries induced by "head-up tilt" in patients with occlusive arterial disease of the legs

    DEFF Research Database (Denmark)

    Agerskov, K; Henriksen, O; Tønnesen, K H

    1981-01-01

    not change the pressure gradient from femoral to popliteal artery in the patients with occlusion of the superficial femoral artery, indicating that the flow resistance offered by the collateral arteries had increased. In a bilateral sympathectomised patient the increase in collateral resistance was almost...... absent indicating that the constriction of the collateral arteries is mainly mediated via sympathetic vasoconstrictor fibres....

  18. The left ventricular contractility of the rat heart is modulated by changes in flow and a1-adrenoceptor stimulation

    Directory of Open Access Journals (Sweden)

    P.F. Vassallo

    1998-10-01

    Full Text Available Myocardial contractility depends on several mechanisms such as coronary perfusion pressure (CPP and flow as well as on a1-adrenoceptor stimulation. Both effects occur during the sympathetic stimulation mediated by norepinephrine. Norepinephrine increases force development in the heart and produces vasoconstriction increasing arterial pressure and, in turn, CPP. The contribution of each of these factors to the increase in myocardial performance needs to be clarified. Thus, in the present study we used two protocols: in the first we measured mean arterial pressure, left ventricular pressure and rate of rise of left ventricular pressure development in anesthetized rats (N = 10 submitted to phenylephrine (PE stimulation before and after propranolol plus atropine treatment. These observations showed that in vivo a1-adrenergic stimulation increases left ventricular-developed pressure (Pa1-adrenoceptors and increased flow, increased cardiac performance acting simultaneously and synergistically.

  19. Synergism of diabetic and inflammatory culture conditions on reactivity of isolated small arteries

    DEFF Research Database (Denmark)

    Blædel, Martin Mads; Boonen, Harrie C.M.; Sams Nielsen, Anette

    Background: Cardiovascular disease (CVD) is the manifestation of atherosclerosis, which has been linked to obesity, the metabolic syndrome (MS) and overt type 2 diabetes (T2DM). Vascular dysfunction has been proposed to precede atherosclerosis, and in addition, a correlation between vascular...... isolated from 8 week old male SD rats were cultured for 21 hours in Endothelial Basal Medium (EBM-2) in petri dishes and in the absence or presence of either 30 mM D-glucose, 100 nM insulin, 100 ng/mL TNFa or any combination of these. Contractile reactivity of normalised arteries was then determined...... by wire myography as a response to cumulatively increasing concentrations of noradrenaline (NA). Results: 21 hour culture of isolated mesenteric arteries significantly reduced the arteries maximal high potassium-induced contractile reactivity and increased the contractility to noradrenaline slightly...

  20. Inhalation of Budesonide/Formoterol Increases Diaphragm Muscle Contractility

    Directory of Open Access Journals (Sweden)

    Chiyohiko Shindoh

    2012-01-01

    Conclusions: BUD/FORM inhalation has an inotropic effect on diaphragm muscle, protects diaphragm muscle deterioration after endotoxin injection, and inhibits NO production. Increments in muscle contractility with BUD/FORM inhalation are induced through a synergistic effect of an anti-inflammatory agent and 02-agonist.

  1. Regional gastrointestinal contractility parameters using the wireless motility capsule

    DEFF Research Database (Denmark)

    Farmer, A D; Wegeberg, A-M L; Brock, B

    2018-01-01

    BACKGROUND: The wireless motility capsule concurrently measures temperature, pH and pressure as it traverses the gastrointestinal tract. AIMS: To describe normative values for motility/contractility parameters across age, gender and testing centres. METHODS: Healthy participants underwent a stand...

  2. Clinical Relationship between Steatocholecystitis and Gallbladder Contractility Measured by Cholescintigraphy

    Directory of Open Access Journals (Sweden)

    Chang Seok Bang

    2015-01-01

    Full Text Available Objective. Contractility of gallbladder is known to be decreased in fatty gallbladder diseases. However, clinical estimation data about this relationship is still lacking. The aim of this study was to investigate the association between steatocholecystitis and contractility of gallbladder. Methods. Patients with cholecystitis (steatocholecystitis versus nonsteatocholecystitis who underwent cholescintigraphy before cholecystectomy were retrospectively evaluated in a single teaching hospital of Korea. The association of steatocholecystitis with contractility of gallbladder, measured by preoperative cholescintigraphy, was assessed by univariable and multivariable analysis. Results. A total of 432 patients were finally enrolled (steatocholecystitis versus nonsteatocholecystitis; 75 versus 357, calculous versus acalculous cholecystitis; 316 versus 116. In the multivariable analysis, age (OR: 0.94, 95% CI: 0.90–0.99, P=0.01 and total serum cholesterol (OR: 1.02, 95% CI: 1.01–1.04, P=0.04 were related to steatocholecystitis in patients with acalculous cholecystitis. Only age (OR: 0.97, 95% CI: 0.94–0.99, P=0.004 was significantly related to steatocholecystitis in patients with calculous cholecystitis. However, ejection fraction of gallbladder reflecting contractility measured by cholescintigraphy was not related to steatocholecystitis irrespective of presence of gallbladder stone in patients with cholecystitis. Conclusion. Ejection fraction of gallbladder measured by cholescintigraphy cannot be used for the detection or confirmation of steatocholecystitis.

  3. Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension

    NARCIS (Netherlands)

    Fowler, Ewan D.; Benoist, David; Drinkhill, Mark J.; Stones, Rachel; Helmes, Michiel; Wüst, Rob C. I.; Stienen, Ger J. M.; Steele, Derek S.; White, Ed

    2015-01-01

    Our objective was to investigate the role of creatine kinase in the contractile dysfunction of right ventricular failure caused by pulmonary artery hypertension. Pulmonary artery hypertension and right ventricular failure were induced in rats by monocrotaline and compared to saline-injected control

  4. New insights on pyrimidine signalling within the arterial vasculature

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Spray, Stine; Syberg, Susanne

    2016-01-01

    and relaxation in the coronary circulation and to establish whether P2Y receptors have different functions along the mouse coronary vascular tree. We tested stable pyrimidine analogues on isolated coronary arteries from P2Y2 and P2Y6 receptor KO mice in a myograph setup. In larger diameter segments of the left...... descending coronary artery (LAD) (lumen diameter~150μm) P2Y6 is the predominant contractile receptor for both UTP (uridine triphosphate) and UDP (uridine diphosphate) induced contraction. In contrast, P2Y2 receptors mediate endothelial-dependent relaxation. However, in smaller diameter LAD segments (lumen...... a biphasic response to the stable analogue UDPβS. Based on the changes in P2Y receptor functionality along the mouse coronary arterial vasculature, we propose that UTP can act as a vasodilator downstream of its release, after being degraded to UDP, without affecting the contractile pyrimidine receptors. We...

  5. Fatigue resistance of the knee extensor muscles is not reduced in post-polio syndrome.

    Science.gov (United States)

    Voorn, Eric L; Beelen, Anita; Gerrits, Karin H L; Nollet, Frans; de Haan, Arnold

    2013-11-01

    The present study investigated whether intrinsic fatigability of the muscle fibers is reduced in patients with post-polio syndrome (PPS). This may contribute to the muscle fatigue complaints reported by patients with PPS. For this purpose, we assessed contractile properties and fatigue resistance of the knee extensor muscles using repeated isometric electrically evoked contractions in 38 patients with PPS and 19 age-matched healthy subjects. To determine whether any difference in fatigue resistance between both groups could be attributed to differences in aerobic capacity of the muscle fibers, 9 patients with PPS and 11 healthy subjects performed the same protocol under arterial occlusion. Results showed that fatigue resistance of patients with PPS was comparable to that in controls, both in the situation with intact circulation and with occluded blood flow. Together, our findings suggest that there are no differences in contractile properties and aerobic muscle capacity that may account for the increased muscle fatigue perceived in PPS. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Epigenetic Reprogramming of Human Embryonic Stem Cells into Skeletal Muscle Cells and Generation of Contractile Myospheres

    Directory of Open Access Journals (Sweden)

    Sonia Albini

    2013-03-01

    Full Text Available Direct generation of a homogeneous population of skeletal myoblasts from human embryonic stem cells (hESCs and formation of three-dimensional contractile structures for disease modeling in vitro are current challenges in regenerative medicine. Previous studies reported on the generation of myoblasts from ESC-derived embryoid bodies (EB, but not from undifferentiated ESCs, indicating the requirement for mesodermal transition to promote skeletal myogenesis. Here, we show that selective absence of the SWI/SNF component BAF60C (encoded by SMARCD3 confers on hESCs resistance to MyoD-mediated activation of skeletal myogenesis. Forced expression of BAF60C enables MyoD to directly activate skeletal myogenesis in hESCs by instructing MyoD positioning and allowing chromatin remodeling at target genes. BAF60C/MyoD-expressing hESCs are epigenetically committed myogenic progenitors, which bypass the mesodermal requirement and, when cultured as floating clusters, give rise to contractile three-dimensional myospheres composed of skeletal myotubes. These results identify BAF60C as a key epigenetic determinant of hESC commitment to the myogenic lineage and establish the molecular basis for the generation of hESC-derived myospheres exploitable for “disease in a dish” models of muscular physiology and dysfunction.

  7. O-GlcNAcylation, contractile protein modifications and calcium affinity in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Caroline eCieniewski-Bernard

    2014-10-01

    Full Text Available Phosphorylation is recognized as being one of the major post-translational modification involved in the fine modulation of all if not all cellular processes including skeletal muscle contractile activity. However, phosphorylation presents a dynamic and highly regulated interplay with an atypical glycosylation on intracellular proteins, the O-GlcNAcylation. Akin to phosphorylation, O-GlcNAcylation is also involved in the physiopathology of several acquired diseases, such as muscle insulin resistance in diabetes or muscle atrophy. Recent data underline that the interplay between phosphorylation and O-GlcNAcylation acts as a modulator of skeletal muscle contractile activity. In particular, the O-GlcNAcylation level of the phosphoprotein MLC2 seems to be crucial in the modulation of the calcium activation properties, and should be responsible of changes in calcium properties observed in atrophy. Moreover, since several key structural proteins are O-GlcNAc-modified, and because of the localization of the enzymes involved in the O-GlcNAcylation/de-O-GlcNAcylation process to the nodal Z disk, a role of O-GlcNAcylation in the modulation of the sarcomeric structure should be considered.

  8. The Effect of Ischemia and Reperfusion on Enteric Glial Cells and Contractile Activity in the Ileum.

    Science.gov (United States)

    Mendes, Cristina Eusébio; Palombit, Kelly; Vieira, Cátia; Silva, Isabel; Correia-de-Sá, Paulo; Castelucci, Patricia

    2015-09-01

    We investigated the effects of ischemia followed by different periods of reperfusion (I/R) on immunoreactive S100β-positive glial and Hu-immunoreactive neurons co-expressing the P2X2 receptor in the myenteric plexus of the rat ileum. The ileal artery was occluded for 35 min with an atraumatic vascular clamp. The animals were killed 24 h, 72 h, and 1 week after ischemia. Sham animals were not submitted to ileal artery occlusion. The relative density, size, and co-localization of P2X2 receptor-expressing cells in relation to S100β-immunoreactive glial and Hu-immunoreactive neuronal cells were evaluated. Additionally, we analyzed the effects of I/R on gastrointestinal transit and ileum contractile activity. The cellular density of P2X2 receptor and neuronal Hu immunoreactivity/cm(2) decreased after I/R, whereas glial S100β immunoreactivity/cm(2) increased. No significant differences between sham and I/R groups were observed regarding the perikarya area of Hu-positive neurons. The area of S100β-immunoreactive glial cells increased by 24.1 % 1 week after I/R compared with the 24 h group. Methylene blue progression along the small intestine decreased (P glial cells, may contribute to decreased GI motility after I/R.

  9. Accuracy of Dobutamine Stress Echocardiography in Detecting Recovery of Contractile Reserve after Revascularization of Ischemic Myocardium

    Directory of Open Access Journals (Sweden)

    Abas Ali karimi

    2007-09-01

    Full Text Available Background: This study was designed to investigate the accuracy of dobutamine stress echocardiography (DSE in detecting the post-revascularization recovery rate of contractile reserve (CR in ischemic myocardium. Methods: A total of 112 segments from seven patients with low ejection fraction (<35% and coronary artery disease were evaluated with DSE one week before and 12 weeks after coronary artery bypass graft surgery (CABG. Sensitivity, specificity, and positive and negative predictive values of DSE for detecting the recovery rate of CR were calculated based upon their standard definition and were presented with 95% confidence intervals (CI. Results: The mean baseline left ventricular ejection fraction was 31±4%, which reached 35±7% after CABG unremarkably. The recovery rates of resting function and CR were 18.2% and 50% for hypokinetic and 15.6% and 24.1 for akinetic segments respectively. Specificity, sensitivity, and positive and negative predictive values of DSE for detecting the recovery of CR were 83% (CI=69-97, 89% (CI=83-96, 94% (CI = 88-99, and 73 % (CI = 55-88, respectively. Conclusion: Despite acceptable sensitivity, specificity, and positive predictive value, DSE has a relatively lower negative predictive value for detecting the recovery of CR in ischemic myocardium and, consequently, the full extent of myocardial viability. Further sensitive techniques may, therefore, be needed to provide complementary information regarding long-term functional outcome.

  10. Increased salt intake during early ontogenesis lead to development of arterial hypertension in salt-resistant Wistar rats.

    Science.gov (United States)

    Svitok, Pavel; Molcan, Lubos; Vesela, Anna; Kruzliak, Peter; Moravcik, Roman; Zeman, Michal

    2015-01-01

    A direct relationship exists between salt consumption and hypertension. Increased sodium intake does not automatically lead to a rise in blood pressure (BP) because of marked intra-individual variability in salt sensitivity. Wistar rats are a salt-resistant strain and increased salt intake in adults does not induce hypertension. Mechanisms regulating BP develop during early ontogenesis and increased sodium consumption by pregnant females leads to an increase in BP of their offspring, but early postnatal stages have not been sufficiently analyzed in salt-resistant strains of rats. The aim of this work was to study the effects of increased salt during early ontogeny on cardiovascular characteristics of Wistar rats. We used 16 control (C; 8 males + 8 females) rats fed with a standard diet (0.2% sodium) and 16 experimental (S; 8 males + 8 females) rats fed with a diet containing 0.8% sodium. BP was measured weekly and plasma renin activity, aldosterone and testosterone concentrations were assayed by radioimmunoassay after the experiment in 16-week-old animals. In the kidney, AT1 receptors were determined by the western blot. BP was higher in the S as compared with the C rats and did not differ between males and females. The relative left ventricle mass was increased in S as compared with C males and no differences were recorded in females. No significant differences between groups were found in hormonal parameters and AT1 receptors. Results indicate that moderately increased salt intake during postnatal ontogeny results in a BP rise even in salt-resistant rats.

  11. Different postprandial lipid metabolism and insulin resistance between non-diabetic patients with and without coronary artery disease.

    Science.gov (United States)

    Nakamura, Akihiro; Monma, Yuto; Kajitani, Shoko; Kozu, Katsuya; Ikeda, Shohei; Noda, Kazuki; Nakajima, Sota; Endo, Hideaki; Takahashi, Tohru; Nozaki, Eiji

    2015-11-01

    Postprandial hyperlipidemia and hyperinsulinemia have been thought to play an important role in the development of atherosclerosis. Diabetes mellitus (DM) has an impact on lipid metabolism, however, little is known about the relationship between the postprandial lipid and glucose metabolism in normoglycemic patients with coronary artery disease (CAD). To compare the postprandial lipid and glucose metabolism in normoglycemic patients with and without CAD, a total of 36 normoglycemic patients: 19 patients with stable CAD (CAD group, age 60.2±11.3 years) and 17 patients without CAD (Non-CAD group, age 60.4±9.6 years) were loaded with a high-fat and high-glucose test meal, and the changes in serum level of the lipid and glucose parameters were monitored before and 0, 2, 4, and 6h later. In the Non-CAD group, postprandial serum levels of triglycerides (TG) and remnant-like particle cholesterol increased significantly and reached peak levels at the 4th hour and decreased significantly at the 6th hour of observation, whereas those levels in CAD group kept rising during 6h of observation. Although there was no significant difference in the area under the curves (AUCs) for the postprandial plasma glucose levels between CAD and Non-CAD group, the AUCs for the postprandial plasma insulin and C-peptide levels were significantly higher in the CAD group than in the Non-CAD group. The AUCs for postprandial TG levels showed good correlation with those for postprandial plasma insulin and C-peptide levels (insulin: r=0.455, ppostprandial hyperlipidemia and hyperinsulinemia may have a close relationship in CAD patients without DM and might play an important role in the development of atherosclerosis even before the onset of diabetes. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  12. Exercícios resistidos terapêuticos para indivíduos com doença arterial obstrutiva periférica: evidências para a prescrição Therapeutic resistance exercises for individuals with peripheral arterial obstructive disease: evidence for prescription

    Directory of Open Access Journals (Sweden)

    Lucas Caseri Câmara

    2007-09-01

    Full Text Available A prática regular de exercícios é parte do tratamento clínico inicial para pacientes com doença arterial obstrutiva periférica. Nesse sentido, a utilização de exercícios contra resistência (exercícios resistidos tem sido amplamente recomendada para diferentes populações, especialmente para pessoas idosas com e sem doenças associadas. Os poucos trabalhos encontrados utilizando essa forma de exercícios em pacientes com doença arterial obstrutiva periférica documentam a sua eficiência terapêutica. No entanto, os efeitos documentados dos exercícios resistidos em outras populações têm evidenciado melhoria da aptidão física e da qualidade de vida, com segurança cardiovascular e músculo-esquelética. Essas informações fornecem indicativos sobre os possíveis benefícios dos exercícios resistidos na terapia de indivíduos com doença arterial obstrutiva periférica. Nesse sentido, esta revisão objetivou apresentar informações científicas que permitam auxiliar a prescrição dos exercícios resistidos para essa população.A regular physical activity program is part of the initial clinical approach to patients with peripheral arterial obstructive disease. Therefore, use of exercises against resistance loads (resistance training has been widely recommended for different populations, especially for elderly individuals with and without associated diseases. The few studies that have used this form of exercise in patients with peripheral arterial obstructive disease demonstrated its therapeutic efficiency. However, reported effects of resistance training in other populations have evidenced improvement in physical fitness and quality of life, with cardiovascular and musculoskeletal safety. These data indicate the possible benefits of resistance training in peripheral arterial obstructive disease therapy. Thus, this review aimed at presenting scientific information that can help prescription of resistance training for this

  13. Liver cirrhosis and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2006-01-01

    Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of...

  14. Arterial management.

    Science.gov (United States)

    2004-04-01

    In many major metropolitan areas, the freeway system is : functioning at or beyond the capacity for which it was : designed. Many drivers are choosing to use arterial streets : instead. The resulting stress on the arterial systems creates : gridlock ...

  15. Effects of resistance training on muscle strength, exercise capacity, and mobility in middle-aged and elderly patients with coronary artery disease: A meta-analysis.

    Science.gov (United States)

    Yamamoto, Shuhei; Hotta, Kazuki; Ota, Erika; Mori, Rintaro; Matsunaga, Atsuhiko

    2016-08-01

    Resistance training (RT) is a core component of cardiac rehabilitation. We investigated the effects of RT on exercise capacity, muscle strength, and mobility in middle-aged and elderly patients with coronary artery disease (CAD). We searched for randomized controlled trials of RT versus usual care, or combined RT and aerobic training (AT) versus AT alone, and identified 440 trials in total from inception to January 2014. Participants who had myocardial infarction, coronary revascularization, angina pectoris or CAD were included in the analysis. Those who had heart failure, heart transplants with either cardiac resynchronization therapy or implantable defibrillators were excluded. Twenty-two trials totaling 1095 participants were analyzed. We performed random-effects meta-analysis. In middle-aged participants, RT increased lower extremity muscle strength [standardized mean difference (SMD): 0.65, 95% confidence interval (CI): 0.35 to 0.95], upper extremity muscle strength (SMD: 0.73, 95% CI: 0.48 to 0.99) and peak oxygen consumption (VO2) [weight mean difference (WMD): 0.92mL/kg/min, 95% CI: 0.12 to 1.72], but did not improve mobility compared with the control. In elderly participants, RT increased lower extremity muscle strength (SMD: 0.63, 95% CI: 0.05 to 1.21), upper extremity muscle strength (SMD: 1.18, 95% CI: 0.56 to 1.80), and peak VO2 (WMD: 0.70mL/kg/min, 95% CI: 0.03 to 1.37), and improved mobility (SMD: 0.61, 95% CI: 0.21 to 1.01) compared with the control. Resistance training could increase exercise capacity and muscle strength in middle-aged and elderly patients, and mobility in elderly patients, with CAD. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  16. Expression of Drug-Resistant Factor Genes in Hepatocellular Carcinoma Patients Undergoing Chemotherapy with Platinum Complex by Arterial Infusion

    Directory of Open Access Journals (Sweden)

    Shiro Ueda

    2010-09-01

    Full Text Available This study investigated gene expression of drug resistance factors in biopsy tissue samples from hepatocellular carcinoma (HCC patients undergoing chemotherapy by platinum complex. Liver biopsy was performed to collect tissue from the tumor site (T and the non-tumor site (NT prior to the start of treatment. For drug-resistant factors, drug excretion transporters cMOAT and MDR-1, intracellular metal binding protein MT2, DNA repair enzyme ERCC-l and inter-nucleic cell transport protein MVP, were investigated. The comparison of the expression between T and NT indicated a significant decrease of MT2 and MDR-1 in T while a significant increase in ERCC-1 was noted in T. Further, expression was compared between the response cases and non-response cases using the ratios of expression in T to those in NT. The response rate was significantly low in the high expression group when the cutoff value of cMOAT and MT2 was set at 1.5 and 1.0, respectively. Furthermore, when the patients were classified into A group (cMOAT ≧ 1.5 or MT2 ≧ 1.0 and B group (cMOAT < 1.5 and MT2 < 1.0, the response rate of A group was significantly lower than B group when we combined the cutoff values of cMOAT and MT2. It is considered possible to estimate the therapeutic effect of platinum complex at a high probability by combining the expression condition of these two genes.

  17. Impact of Severe Thermal Injury on Cardiac Contractility and Metabolism

    Directory of Open Access Journals (Sweden)

    M. A. Goldzon

    2011-01-01

    Full Text Available Objective: to experimentally study cardiac functional and metabolic disturbances in the acute period of severe thermal injury. Material and methods. Experiments were carried out on 25 outbred male albino rats anesthesized with Nembutal (50 mg/kg intraperitoneally. Five-mm-thick copper plates heated up to 60°C were used to simulate thermal injury. Skin contact with the thermal agent lasted 15 seconds. Myocardial contractility and metabolism were examined using the specimen of the isolated isovolumically contracted heart. Results. Severe thermal injury was found to induce acute heart failure caused by cardiac bioenergy impairment, hypoxia, metabolic acidosis, and cardiomyocyte membrane destruction. Key words: thermal injury, cardiac contractility and metabolism.

  18. Disordered Actomyosin Is Sufficient to Promote Cooperative and Telescopic Contractility

    Science.gov (United States)

    Murrell, Michael; Linsmeier, Ian; Banerjee, Shiladitya; Kim, Tae Yoon; Jung, Wonyeong; Oakes, Patrick

    While the molecular interactions between myosin motors and F-actin are well known, the relationship between F-actin organization and myosin-mediated force generation remains poorly understood. Here, we explore the accumulation of myosin-induced stresses within a 2D biomimetic model of the actomyosin cortex, where myosin activity is controlled spatially and temporally using light. By controlling the geometry and the duration of myosin activation, we show that contraction of disordered actomyosin is highly cooperative, telescopic with the activation area and generates a pattern of mechanical stresses consistent with those observed in contractile cells. We quantitatively reproduce these properties using an in vitro isotropic model of the actomyosin cytoskeleton, and explore the physical origins of telescopic contractility in disordered networks using agent-based simulations. NSF CMMI-1525316.

  19. Spontaneous oscillations of elastic contractile materials with turnover.

    Science.gov (United States)

    Dierkes, Kai; Sumi, Angughali; Solon, Jérôme; Salbreux, Guillaume

    2014-10-03

    Single and collective cellular oscillations driven by the actomyosin cytoskeleton have been observed in numerous biological systems. Here, we propose that these oscillations can be accounted for by a generic oscillator model of a material turning over and contracting against an elastic element. As an example, we show that during dorsal closure of the Drosophila embryo, experimentally observed changes in actomyosin concentration and oscillatory cell shape changes can, indeed, be captured by the dynamic equations studied here. We also investigate the collective dynamics of an ensemble of such contractile elements and show that the relative contribution of viscous and friction losses yields different regimes of collective oscillations. Taking into account the diffusion of force-producing molecules between contractile elements, our theoretical framework predicts the appearance of traveling waves, resembling the propagation of actomyosin waves observed during morphogenesis.

  20. Effect of Aloe Barbadensis on Rat's Uterine Contractility | Iranloye ...

    African Journals Online (AJOL)

    The present study was undertaken to investigate the effect of the aqueous extract of Aloe barbadensis on the contractility of the uterine stip of a rat. Aqueous extract at final bath concentrations (FBC)1x10-4 mg/ml to 3x101 mg/ml produced a progressive increase in frequency of contraction of the uterine strip. The force of ...

  1. Does phototherapy enhance skeletal muscle contractile function and postexercise recovery? A systematic review.

    Science.gov (United States)

    Borsa, Paul A; Larkin, Kelly A; True, Jerry M

    2013-01-01

    Recently, researchers have shown that phototherapy administered to skeletal muscle immediately before resistance exercise can enhance contractile function, prevent exercise-induced cell damage, and improve postexercise recovery of strength and function. To critically evaluate original research addressing the ability of phototherapeutic devices, such as lasers and light-emitting diodes (LEDs), to enhance skeletal muscle contractile function, reduce exercise-induced muscle fatigue, and facilitate postexercise recovery. We searched the electronic databases PubMed, SPORTDiscus, Web of Science, Scopus, and Rehabilitation & Physical Medicine without date limitations for the following key words: laser therapy, phototherapy, fatigue, exercise, circulation, microcirculation, and photobiomodulation. Eligible studies had to be original research published in English as full papers, involve human participants, and receive a minimum score of 7 out of 10 on the Physiotherapy Evidence Database (PEDro) scale. Data of interest included elapsed time to fatigue, total number of repetitions to fatigue, total work performed, maximal voluntary isometric contraction (strength), electromyographic activity, and postexercise biomarker levels. We recorded the PEDro scores, beam characteristics, and treatment variables and calculated the therapeutic outcomes and effect sizes for the data sets. In total, 12 randomized controlled trials met the inclusion criteria. However, we excluded data from 2 studies, leaving 32 data sets from 10 studies. Twenty-four of the 32 data sets contained differences between active phototherapy and sham (placebo-control) treatment conditions for the various outcome measures. Exposing skeletal muscle to single-diode and multidiode laser or multidiode LED therapy was shown to positively affect physical performance by delaying the onset of fatigue, reducing the fatigue response, improving postexercise recovery, and protecting cells from exercise-induced damage

  2. Intrauterine Telemetry to Measure Mouse Contractile Pressure In Vivo

    Science.gov (United States)

    Rada, Cara C.; Pierce, Stephanie L.; Grotegut, Chad A.; England, Sarah K.

    2015-01-01

    A complex integration of molecular and electrical signals is needed to transform a quiescent uterus into a contractile organ at the end of pregnancy. Despite the discovery of key regulators of uterine contractility, this process is still not fully understood. Transgenic mice provide an ideal model in which to study parturition. Previously, the only method to study uterine contractility in the mouse was ex vivo isometric tension recordings, which are suboptimal for several reasons. The uterus must be removed from its physiological environment, a limited time course of investigation is possible, and the mice must be sacrificed. The recent development of radiometric telemetry has allowed for longitudinal, real-time measurements of in vivo intrauterine pressure in mice. Here, the implantation of an intrauterine telemeter to measure pressure changes in the mouse uterus from mid-pregnancy until delivery is described. By comparing differences in pressures between wild type and transgenic mice, the physiological impact of a gene of interest can be elucidated. This technique should expedite the development of therapeutics used to treat myometrial disorders during pregnancy, including preterm labor. PMID:25867820

  3. Multicellular contractility contributes to the emergence of mesothelioma nodules

    Science.gov (United States)

    Czirok, Andras

    Malignant pleural mesothelioma (MPM) nodules arise from the mesothelial lining of the pleural cavity by a poorly understood mechanism. We demonstrate that macroscopic multicellular aggregates, reminiscent of the MPM nodules found in patients, develop when MPM cell lines are cultured at high cell densities for several weeks. Surprisingly, the nodule-like aggregates do not arise by excessive local cell proliferation, but by myosin II-driven cell contractility. Contractile nodules contain prominent actin cables that can span several cells. Several features of the in vitro MPM nodule development can be explained by a computational model that assumes uniform and steady intercellular contractile forces within a monolayer of cells, and a mechanical load-dependent lifetime of cell-cell contacts. The model behaves as a self-tensioned Maxwell fluid and exhibits an instability that leads to pattern formation. Altogether, our findings suggest that inhibition of the actomyosin system may provide a hitherto not utilized therapeutic approach to affect MPM growth. NIH R01-GM102801.

  4. Small Artery Remodeling: Current Concepts and Questions

    NARCIS (Netherlands)

    van den Akker, Jeroen; Schoorl, Marieke J. C.; Bakker, Erik N. T. P.; VanBavel, Ed

    2010-01-01

    Blood flow regulation by small arteries and arterioles includes adaptation of both vascular tone and structure. It is becoming clear that tone and remodeling of resistance vessels are highly interrelated. Indeed, concepts pointing to continuous resistance artery adaptation and plasticity are

  5. Considerações sobre a medida da pressão arterial em exercícios contra-resistência

    Directory of Open Access Journals (Sweden)

    Polito Marcos Doederlein

    2003-01-01

    Full Text Available A pressão arterial (PA é uma variável cuja quantificação em sessões de treinamento é desejável, já que tem relação com as demandas cardiovasculares no esforço. No caso de exercícios contra-resistência (ECR, porém, os valores obtidos estão sujeitos a erros, dependendo da técnica de medida adotada. Este texto tem por objetivo revisar os métodos de medida da PA no ECR, sugerindo formas de reduzir as discrepâncias das medidas indiretas quando comparadas com o método direto. A medida direta da PA é feita por cateterismo intra-arterial (CI. Este método é tido como padrão-ouro mas, devido a sua natureza invasiva, é um procedimento pouco usual. Além disso, sua aplicação não seria indicada em indivíduos assintomáticos, uma vez associada a riscos de dor, espasmo e oclusão arterial, síncope vasovagal e sangramento. Dentre os métodos indiretos, destacam-se o fotoplestimográfico (Finapres e o auscultatório (MA. Poucos são os estudos comparativos entre esses procedimentos de medida durante ECR, a ênfase sendo maior em atividades aeróbias e no repouso. Dentre os estudos revisados, não foram localizados trabalhos comparando o CI com Finapres durante ECR e apenas três com o método auscultatório. Em suma, o CI parece pouco viável e ético para quantificar a PA em ECR. O Finapres é considerado o melhor procedimento indireto, mas depende de equipamento, cujo custo é elevado e a fabricação, suspensa. O MA pode subestimar o valor real da PA, em função de limitações inerentes à técnica e das características dos exercícios observados. No entanto, alguns procedimentos durante a mensuração podem reduzir essas diferenças, como realizá-la o mais tardiamente possível, antes do término do exercício. Enfim, apesar das discrepâncias referentes aos valores absolutos, as medidas obtidas pelo método auscultatório podem ser sensíveis para identificar tendências do impacto sobre a PA, decorrentes de diferentes

  6. Effects of 6 months of aerobic and resistance exercise training on carotid artery intima media thickness in overweight and obese older women.

    Science.gov (United States)

    Park, Jinkee; Park, Hyuntea

    2017-12-01

    We studied the effects of exercise on carotid intima-media thickness, luminal diameter, and flow velocity in overweight and obese older women, and the associations between carotid parameters changes and other variables. A total of 41 overweight and obese older women (aged 65-77 years, fat mass percent ≥ 32%), who were divided into a control group (n = 20) and a supervised combined exercise group (n = 21). The 24-week combined exercise program (aerobic and resistance exercise) consisted of sessions 40-80 min in length 5 days per week under the supervision of an exercise specialist. Body composition, blood pressure, physical function and carotid variables were assessed. The differences in all variables, and the relative changes between baseline and 24 weeks' follow up were evaluated. Carotid intima-media thickness, systolic carotid luminal diameter, peak systolic flow velocity and end diastolic flow velocity showed a significant group × time interaction. No interaction was observed for diastolic luminal diameter. In the exercise group, the change of carotid intima-media thickness was significantly associated with systolic blood pressure, maximal walking speed, 1-mile walking time and maximal oxygen uptake. Also, the change of peak systolic flow velocity was significantly associated with skeletal muscle mass, diastolic blood pressure and maximum walking speed. Combined exercise can effectively improve carotid intima-media thickness in overweight and obese older women. In addition, exercise training increases the systolic carotid luminal diameter and flow velocity in older women. Therefore, regular combined exercise might help prevent atherosclerotic disease by improving the carotid artery. Geriatr Gerontol Int 2017; 17: 2304-2310. © 2017 Japan Geriatrics Society.

  7. Cardiac output and blood volume parameters using femoral arterial thermodilution.

    Science.gov (United States)

    López-Herce, Jesús; Bustinza, Amaya; Sancho, Luis; Mencía, Santiago; Carrillo, Angel; Moral, Ramón; Bellón, Jose María

    2009-02-01

    The pulse-induced continuous cardiac output (PiCCO) system is a less invasive method than pulmonary thermodilution for the measurement of cardiac output and estimating blood volume parameters. The normal values in children have not been defined. The purpose of the present paper was therefore to evaluate cardiac output and parameters of blood volume using femoral arterial thermodilution in critically ill children. A prospective study was performed in 17 critically ill children aged between 2 months and 14 years. Two measurements were taken for each determination of cardiac output, global end diastolic volume (GEDVI), intrathoracic blood volume index (ITBI), extravascular lung water index (ELWI), systolic volume index (SVI), stroke volume variation (SVV), cardiac function index (CFI), left ventricular contractility (dp/dt max), and the systemic vascular resistance index (SVRI). One hundred and seventeen measurements were performed. The mean cardiac index (CI) was 3.5 +/- 1.3 L/min per m(2). The GEDVI (399.7 +/- 349.1 mL/m(2)), ITBI (574.5 +/- 212.2 mL/m(2)) and dp/dt max (804.6 +/- 372.1 mmHg/s) were lower than reported in adults, whereas ELWI (18.9 +/- 9.3 mL/m2) and CFI (8 +/- 2.5 L/min) where higher. The GEDVI, SVI, dp/dt max and CI increased with the weight of the patients whereas the ELWI values decreased. Femoral arterial thermodilution is a suitable technique for the measurement of cardiac output in critically ill children. The intrathoracic and intracardiac volumes are lower than in adults, whereas extrapulmonary water is higher; these values are related to the weight of the patient.

  8. Differences in histamine H1 and H2 receptor responses in several rabbit arteries

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, C.P.; Maxson, S.

    1982-06-01

    Responses of helically cut segments from six different rabbit arteries to the selective histamine H1 receptor agonist 2-pyridylethylamine (PEA) and, in strips contracted by 10-4 M phenylephrine, to the selective histamine H2 agonist dimaprit have been determined. 10-3 M PEA contracted the renal artery, 96 +/- 2%; mesenteric artery, 92 +/- 2%; coeliac artery, 88 +/- 11% aorta 75 +/- 4%' ear artery 64 +/- 10% and pulmonary artery 48 +/- 5% of the maximal contraction to norepinephrine. 10-3 M dimaprit relaxed the phenylephrine contracted ear artery 48 +/- 8%; renal artery, 43 +/- 8%; coeliac artery 41 +/- 8%; mesenteric artery 36 +/- 5%; aorta 16 +/- 3%; and pulmonary artery 11 +/- 1% of the initial contractile tension. Strips in which histamine H1 receptors are blocked by 7 X 10-6 M mepyramine which are contracted by phenylephrine are partially relaxed by histamine. Cooling these strips markedly enhanced relaxations of the mesenteric and coeliac arteries but not those of the other four vessels. Exposure of the strips to dibenamine potentiated relaxations of all of the arteries except the ear artery and pulmonary artery. Thus there is heterogeneity among the arteries in their responses to histamine H1 and H2 receptor activation.

  9. Altered reactivity of resistance vasculature contributes to hypertension in elastin insufficiency.

    Science.gov (United States)

    Osei-Owusu, Patrick; Knutsen, Russell H; Kozel, Beth A; Dietrich, Hans H; Blumer, Kendall J; Mecham, Robert P

    2014-03-01

    Elastin (Eln) insufficiency in mice and humans is associated with hypertension and altered structure and mechanical properties of large arteries. However, it is not known to what extent functional or structural changes in resistance arteries contribute to the elevated blood pressure that is characteristic of Eln insufficiency. Here, we investigated how Eln insufficiency affects the structure and function of the resistance vasculature. A functional profile of resistance vasculature in Eln(+/-) mice was generated by assessing small mesenteric artery (MA) contractile and vasodilatory responses to vasoactive agents. We found that Eln haploinsufficiency had a modest effect on phenylephrine-induced vasoconstriction, whereas ANG II-evoked vasoconstriction was markedly increased. Blockade of ANG II type 2 receptors with PD-123319 or modulation of Rho kinase activity with the inhibitor Y-27632 attenuated the augmented vasoconstriction, whereas acute Y-27632 administration normalized blood pressure in Eln(+/-) mice. Sodium nitroprusside- and isoproterenol-induced vasodilatation were normal, whereas ACh-induced vasodilatation was severely impaired in Eln(+/-) MAs. Histologically, the number of smooth muscle layers did not change in Eln(+/-) MAs; however, an additional discontinuous layer of Eln appeared between the smooth muscle layers that was absent in wild-type arteries. We conclude that high blood pressure arising from Eln insufficiency is due partly to permanent changes in vascular tone as a result of increased sensitivity of the resistance vasculature to circulating ANG II and to impaired vasodilatory mechanisms arising from endothelial dysfunction characterized by impaired endothelium-dependent vasodilatation. Eln insufficiency causes augmented ANG II-induced vasoconstriction in part through a novel mechanism that facilitates contraction evoked by ANG II type 2 receptors and altered G protein signaling.

  10. Nitrate supplementation enhances the contractile properties of human skeletal muscle.

    Science.gov (United States)

    Haider, Georg; Folland, Jonathan P

    2014-12-01

    Dietary nitrate supplementation positively affects cardiovascular function at rest and energy metabolism during exercise in humans and has recently also been reported to markedly enhance the in vitro contractile properties of mouse fast-twitch muscle. The aim of this study was to investigate the effects of short-term nitrate supplementation on the in vivo contractile properties of the skeletal muscle and voluntary muscle function of humans. In a double-blind, randomized, crossover design, 19 healthy untrained men (21 ± 3 yr) ingested a nitrate-rich concentrated beetroot juice (NIT; nitrate dosage, approximately 9.7 mmol·d) and a placebo (PLA) for seven consecutive days. After the last supplementation dose, force was recorded while participants completed a series of voluntary and involuntary (electrically evoked) unilateral isometric contractions of the knee extensors. NIT enhanced the peak force response to low-frequency electrical stimulation, as follows: maximal twitch (NIT, 149 ± 41 N, vs PLA, 138 ± 37 N; P = 0.008; effect size, r (ES) = 0.56) and submaximal 1- to 20-Hz contractions (5%-10%, ES = 0.53-0.63). Whereas explosive (rising phase) force production during the first 50 ms of evoked maximal twitch and octet contractions (eight electrical impulses at 300 Hz) was also 3%-15% greater after NIT compared with that after PLA (P = 0.023-0.048, ES = 0.52-0.59), explosive voluntary force remained similar (P = 0.510, ES = 0.16). Maximum voluntary force was also unchanged after NIT (P = 0.539, ES = 0.15). These results indicate that 7 d of dietary nitrate supplementation enhanced the in vivo contractile properties of the human skeletal muscle. Specifically, nitrate supplementation improved excitation-contraction coupling at low frequencies of stimulation and enhanced evoked explosive force production but did not affect maximum or explosive voluntary force production in untrained individuals.

  11. Effect of beta-alanine and carnosine supplementation on muscle contractility in mice.

    Science.gov (United States)

    Everaert, Inge; Stegen, Sanne; Vanheel, Bert; Taes, Youri; Derave, Wim

    2013-01-01

    Enhanced carnosine levels have been shown to be ergogenic for high-intensity exercise performances, although the role of carnosine in the control of muscle function is poorly understood. Therefore, the aim of this study was to investigate the effect of long-term supplementation with increasing doses of carnosine and beta-alanine on muscle carnosine, anserine, and taurine levels and on in vitro contractility and fatigue in mice. Male Naval Medical Research Institute mice (n = 66) were control fed or supplemented with either carnosine (0.1%, 0.5%, or 1.8%) or beta-alanine (0.6 or 1.2%) in their drinking water for 8-12 wk. Soleus and extensor digitorum longus (EDL) were tested for in vitro contractile properties, and carnosine, anserine, and taurine content were measured in EDL and tibialis anterior by high-performance liquid chromatography. Only supplementation with 1.8% carnosine and 1.2% beta-alanine resulted in markedly higher carnosine (up to +160%) and anserine levels (up to +46%) compared with control mice. Beta-alanine supplementation (1.2%) resulted in increased fatigue resistance in the beginning of the fatigue protocol in soleus (+2%-4%) and a marked leftward shift of the force-frequency relation in EDL (10%-31% higher relative forces). Comparable with humans, beta-alanine availability seems to be the rate-limiting step for synthesis of muscle histidine-containing dipeptides in mice. Moreover, muscle histidine-containing dipeptides loading in mice moderately and muscle dependently affects excitation-contraction coupling and fatigue.

  12. A feasible method for non-invasive measurement of pulmonary vascular resistance in pulmonary arterial hypertension: Combined use of transthoracic Doppler-echocardiography and cardiac magnetic resonance. Non-invasive estimation of pulmonary vascular resistance.

    Science.gov (United States)

    Yan, Chaowu; Xu, Zhongying; Jin, Jinglin; Lv, Jianhua; Liu, Qiong; Zhu, Zhenhui; Pang, Kunjing; Shi, Yisheng; Fang, Wei; Wang, Yang

    2015-12-07

    Transthoracic Doppler-echocardiography (TTE) can estimate mean pulmonary arterial pressure (MPAP) and pulmonary capillary wedge pressure (PCWP) reliably, and cardiac magnetic resonance (CMR) is the best modality for non-invasive measurement of cardiac output (CO). We speculated that the combined use of TTE and CMR could provide a feasible method for non-invasive measurement of pulmonary vascular resistance (PVR) in pulmonary arterial hypertension (PAH). Right heart catheterization (RHC) was undertaken in 77 patients (17M/60F) with PAH, and simultaneous TTE was carried out to evaluate MPAP, PCWP and CO. Within 2 days, CO was measured again with CMR in similar physiological status. Then, PVR was calculated with the integrated non-invasive method: TTE-derived (MPAP-PCWP)/CMR-derived CO and the isolated TTE method: TTE-derived (MPAP-PCWP)/TTE-derived CO, respectively. The PVR calculated with integrated non-invasive method correlated well with RHC-calculated PVR (r = 0.931, 95% confidence interval 0.893 to 0.956). Between the integrated non-invasive PVR and RHC-calculated PVR, the Bland-Altman analysis showed the satisfactory limits of agreement (mean value: - 0.89 ± 2.59). In comparison, the limits of agreement were less satisfactory between TTE-calculated PVR and RHC-calculated PVR (mean value: - 1.80 ± 3.33). Furthermore, there were excellent intra- and inter-observer correlations for the measurements of TTE and CMR ( P  TTE and CMR provides a clinically reliable method to determine PVR non-invasively. In comparison with RHC, the integrated method shows good accuracy and repeatability, which suggests the potential for the evaluation and serial follow-up in patients with PAH. In PAH, the non-invasive measurement of PVR is very important in clinical practice. Up to now, however, the widely accepted non-invasive method is still unavailable. Since TTE can estimate (MPAP-PCWP) reliably and CMR is the best image modality for the measurement of CO, the combined

  13. Fiber-type-specific sensitivities and phenotypic adaptations to dietary fat overload differentially impact fast- versus slow-twitch muscle contractile function in C57BL/6J mice

    NARCIS (Netherlands)

    Ciapaite, Jolita; van den Berg, Sjoerd A.; Houten, Sander M.; Nicolay, Klaas; van Dijk, Ko Willems; Jeneson, Jeroen A.

    2015-01-01

    High-fat diets (HFDs) have been shown to interfere with skeletal muscle energy metabolism and cause peripheral insulin resistance. However, understanding of HFD impact on skeletal muscle primary function, i.e., contractile performance, is limited. Male C57BL/6J mice were fed HFD containing lard

  14. Fiber-type-specific sensitivities and phenotypic adaptations to dietary fat overload differentially impact fast- versus slow-twitch muscle contractile function in C57BL/6J mice

    NARCIS (Netherlands)

    Ciapaite, Jolita; van den Berg, Sjoerd A.; Houten, Sander M.; Nicolay, Klaas; van Dijk, Ko Willems; Jeneson, Jeroen

    High-fat diets (HFDs) have been shown to interfere with skeletal muscle energy metabolism and cause peripheral insulin resistance. However, understanding of HFD impact on skeletal muscle primary function, i.e., contractile performance, is limited. Male C57BL/6J mice were fed HFD containing lard

  15. Mechanism of overshoot elevation of left ventricular ejection fraction during recovery after exercise in normal subjects and patients with coronary artery disease, assessed by 99mTc exercise radionuclide ventriculography

    International Nuclear Information System (INIS)

    Kubota, Sachio; Iizuka, Toshio; Isobe, Naoki; Nagaoka, Hideki; Imai, Susumu; Suzuki, Tadashi.

    1995-01-01

    An 'overshoot' (OS) elevation of ejection fraction above resting levels has been demonstrated during recovery after exercise. To characterize the hemodynamic changes during recovery after bicycle exercise, we used radionuclide ventriculography under the Swan-Ganz catheter insertion in 16 normal subjects and 15 patients with coronary artery disease (CAD) at rest, during bicycle exercise and after exercise periods. In normal subjects, the ejection fraction increased from resting value during peak exercise, and showed overshoot elevation in the early recovery period. In patients with CAD, the ejection fraction decreased from resting value during peak exercise, then showed overshoot elevation in the early recovery period. In normal subjects, the end-diastolic volume (EDV) and the end-systolic volume (ESV) decreased from resting value during OS. In patients with CAD, the EDV at OS was not different from that at rest, the ESV decreased from resting value during OS. The systemic vascular resistance increased from resting value during OS. The systolic blood pressure/ESV, index for ventricular contractility, increased from resting value during OS in both groups. Thus, the decreased systemic vascular resistance does not playing a major role during recovery after exercise, whereas enhanced contractility is evident in both normal subjects and patients with CAD. (author)

  16. Resolving the role of actoymyosin contractility in cell microrheology.

    Directory of Open Access Journals (Sweden)

    Christopher M Hale

    2009-09-01

    Full Text Available Einstein's original description of Brownian motion established a direct relationship between thermally-excited random forces and the transport properties of a submicron particle in a viscous liquid. Recent work based on reconstituted actin filament networks suggests that nonthermal forces driven by the motor protein myosin II can induce large non-equilibrium fluctuations that dominate the motion of particles in cytoskeletal networks. Here, using high-resolution particle tracking, we find that thermal forces, not myosin-induced fluctuating forces, drive the motion of submicron particles embedded in the cytoskeleton of living cells. These results resolve the roles of myosin II and contractile actomyosin structures in the motion of nanoparticles lodged in the cytoplasm, reveal the biphasic mechanical architecture of adherent cells-stiff contractile stress fibers interdigitating in a network at the cell cortex and a soft actin meshwork in the body of the cell, validate the method of particle tracking-microrheology, and reconcile seemingly disparate atomic force microscopy (AFM and particle-tracking microrheology measurements of living cells.

  17. Lidocaine decreases the xylazine-evoked contractility in pregnant cows.

    Science.gov (United States)

    Piccinno, M; Rizzo, A; Mutinati, M; D'Onghia, G; Sciorsci, R L

    2016-08-01

    The objective of this in vitro study was to evaluate and compare the effects of xylazine on basal uterine contractility of bovine pregnant uterine strips and that of lidocaine on xylazine-sensitized bovine pregnant uterine strips, at different stages of pregnancy. Basal contractility was evaluated in an isolated organ bath and the functionality of the strips throughout the experiment was evaluated using a dose of carbachol (10(-5)M). Uterine motility, expressed with amplitude, frequency of contractions as well as the area under the curve, was recorded in different stages of pregnancy and data were collected at 15-min intervals (5-min before and 5-min after xylazine administration and 5-min after lidocaine addition on the plateau contraction induced by xylazine). Uterine motility increased in all the stages of pregnancy after xylazine addition and gradually decreased after treatment with lidocaine. These data suggest that lidocaine might decrease the tonic effect induced by xylazine on bovine pregnant uteri. Copyright © 2016. Published by Elsevier Ltd.

  18. Fiber plucking: large emergent contractility in stiff biopolymer networks

    Science.gov (United States)

    Ronceray, Pierre; Broedersz, Chase; Lenz, Martin

    The mechanical properties of the cell depend crucially on the tension of its cytoskeleton. Contractile stresses in this fiber network originate from the forces exerted by active motor proteins. Importantly, experimentally observed cell-scale stresses are much larger than would be expected from linear elastic transmission of the molecular forces. We have recently proposed a mechanism for this nonlinear stress amplification, involving extended filament buckling in the network. We propose here an alternate mechanism: when active forces are exerted transversely on a filament, they induce a nonlinear tension in the plucked fiber. The resulting contractile response in the far-field can overwhelm dramatically the linear stress prediction. Importantly, such a plucking force amplification relies on the surrounding network to be stiff and only moderately stressed. These conditions compete with those required to observe amplification due to fiber buckling. Fiber networks thus provide several distinct pathways for living systems to amplify their molecular forces. Their relative importance in biological relevant situations could be assessed using experimentally testable scaling laws.

  19. Pelvic floor muscle contractility: digital assessment vs transperineal ultrasound.

    Science.gov (United States)

    van Delft, K; Thakar, R; Sultan, A H

    2015-02-01

    A significant reduction in hiatal area and anteroposterior diameter can be induced by pelvic floor muscle contraction, and this has been demonstrated using three-dimensional/four-dimensional (3D/4D) transperineal ultrasound (TPS) in a small group of women. Our objective was to correlate pelvic floor muscle contractility using digital assessment with the change in TPS hiatus measurements during maximum pelvic floor muscle contraction. Nulliparous pregnant women were recruited from the antenatal clinic. Pelvic floor muscle contractility was assessed by digital palpation using the validated Modified Oxford Scale (MOS). Subsequently, women underwent 3D/4D TPS. Measurements of the hiatal area and anteroposterior diameter were taken from the rendered ultrasound images at rest and at maximum contraction, and differences in measurements were expressed as percentages. Spearman's rank (ρ) was used to assess the correlation. Four hundred and fifty-nine assessments were performed, of which 268 were from women at around 36 weeks' gestation, and 191 were from women following delivery at 3 months postpartum. The overall correlation between MOS and TPS was found to be ρ = 0.47 for hiatal area (P biofeedback when training patients in pelvic floor muscle exercises. As TPS is non-intrusive, it may be the method of choice for some women. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

  20. Effect of serotonin on small intestinal contractility in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, M.B.; Arif, F.; Gregersen, H.

    2008-01-01

    The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contrac......The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro......-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase In frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile...

  1. Human Engineered Heart Tissue: Analysis of Contractile Force.

    Science.gov (United States)

    Mannhardt, Ingra; Breckwoldt, Kaja; Letuffe-Brenière, David; Schaaf, Sebastian; Schulz, Herbert; Neuber, Christiane; Benzin, Anika; Werner, Tessa; Eder, Alexandra; Schulze, Thomas; Klampe, Birgit; Christ, Torsten; Hirt, Marc N; Huebner, Norbert; Moretti, Alessandra; Eschenhagen, Thomas; Hansen, Arne

    2016-07-12

    Analyzing contractile force, the most important and best understood function of cardiomyocytes in vivo is not established in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). This study describes the generation of 3D, strip-format, force-generating engineered heart tissues (EHT) from hiPSC-CM and their physiological and pharmacological properties. CM were differentiated from hiPSC by a growth factor-based three-stage protocol. EHTs were generated and analyzed histologically and functionally. HiPSC-CM in EHTs showed well-developed sarcomeric organization and alignment, and frequent mitochondria. Systematic contractility analysis (26 concentration-response curves) reveals that EHTs replicated canonical response to physiological and pharmacological regulators of inotropy, membrane- and calcium-clock mediators of pacemaking, modulators of ion-channel currents, and proarrhythmic compounds with unprecedented precision. The analysis demonstrates a high degree of similarity between hiPSC-CM in EHT format and native human heart tissue, indicating that human EHTs are useful for preclinical drug testing and disease modeling. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. The effects of housing conditions on baseline cardiovascular parameters and the sensitivity to detect changes in contractility in telemetry-implanted dogs.

    Science.gov (United States)

    Sadekova, Nataliya; Boudreau, Ghislaine; Jalbert, Benoit; Norton, Kevin

    2016-01-01

    There is a growing weight of evidence to suggest that myocardial contractility is an important parameter to assess as part of IND enabling studies in addition to standard assessments as per the ICH S7A and S7B guidelines. Historically, assessments of contractility have been limited to snap-shot echocardiography or single housed telemetry assessments of left ventricular pressure. There is a growing number of studies showing that social housing conditions in large animals are beneficial, do not impact the integrity of the data collected and improve animal welfare. With current advances in cardiovascular technology it is now feasible to conduct cardiovascular assessments under group housing conditions. Therefore, the purpose of this study was to evaluate baseline hemodynamic parameters, within a group housed environment, and to demonstrate that the model retains the sensitivity of the traditional assessments. Four animals were instrumented with DSI HD-L21 implants for continuous 24-hour assessment of systemic arterial pressures, left ventricular pressures, heart rate and electrocardiogram intervals in group housed conditions. The animals were administered either Atenolol (0.3, 1 and 3mg/kg), a known negative inotrope, or Pimobendan (0.1, 0.3 and 1mg/kg), a known positive inotrope. The results showed that group housing had no influence on baseline hemodynamic assessments as compared to historical data from single housed animals. The administration of Atenolol and Pimobendan induced the expected changes in cardiovascular parameters. The baseline hemodynamic parameters remained within physiological ranges and were not influenced by group housing conditions. The model retained sensitivity to detect the expected changes in contractility in line with known effects of Atenolol and Pimobendan in dogs. In conclusion, the use of social housing conditions in dogs provides an enriched environment, compliant with animal welfare recommendations, and is in line with the ICH S7A

  3. Liver cirrhosis and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2006-01-01

    blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development......Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release...... of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most...

  4. The effects of hibernation on the contractile and biochemical properties of skeletal muscles in the thirteen-lined ground squirrel, Ictidomys tridecemlineatus.

    Science.gov (United States)

    James, Rob S; Staples, James F; Brown, Jason C L; Tessier, Shannon N; Storey, Kenneth B

    2013-07-15

    Hibernation is a crucial strategy of winter survival used by many mammals. During hibernation, thirteen-lined ground squirrels, Ictidomys tridecemlineatus, cycle through a series of torpor bouts, each lasting more than a week, during which the animals are largely immobile. Previous hibernation studies have demonstrated that such natural models of skeletal muscle disuse cause limited or no change in either skeletal muscle size or contractile performance. However, work loop analysis of skeletal muscle, which provides a realistic assessment of in vivo power output, has not previously been undertaken in mammals that undergo prolonged torpor during hibernation. In the present study, our aim was to assess the effects of 3 months of hibernation on contractile performance (using the work loop technique) and several biochemical properties that may affect performance. There was no significant difference in soleus muscle power output-cycle frequency curves between winter (torpid) and summer (active) animals. Total antioxidant capacity of gastrocnemius muscle was 156% higher in torpid than in summer animals, suggesting one potential mechanism for maintenance of acute muscle performance. Soleus muscle fatigue resistance was significantly lower in torpid than in summer animals. Gastrocnemius muscle glycogen content was unchanged. However, state 3 and state 4 mitochondrial respiration rates were significantly suppressed, by 59% and 44%, respectively, in mixed hindlimb skeletal muscle from torpid animals compared with summer controls. These findings in hindlimb skeletal muscles suggest that, although maximal contractile power output is maintained in torpor, there is both suppression of ATP production capacity and reduced fatigue resistance.

  5. Reliability of contractile properties of the knee extensor muscles in individuals with post-polio syndrome

    NARCIS (Netherlands)

    Voorn, Eric L.; Brehm, Merel A.; Beelen, Anita; de Haan, Arnold; Nollet, Frans; Gerrits, Karin H. L.

    2014-01-01

    To assess the reliability of contractile properties of the knee extensor muscles in 23 individuals with post-polio syndrome (PPS) and 18 age-matched healthy individuals. Contractile properties of the knee extensors were assessed from repeated electrically evoked contractions on 2 separate days, with

  6. Magnetically Bioprinted Human Myometrial 3D Cell Rings as A Model for Uterine Contractility.

    Science.gov (United States)

    Souza, Glauco R; Tseng, Hubert; Gage, Jacob A; Mani, Arunmani; Desai, Pujan; Leonard, Fransisca; Liao, Angela; Longo, Monica; Refuerzo, Jerrie S; Godin, Biana

    2017-03-23

    Deregulation in uterine contractility can cause common pathological disorders of the female reproductive system, including preterm labor, infertility, inappropriate implantation, and irregular menstrual cycle. A better understanding of human myometrium contractility is essential to designing and testing interventions for these important clinical problems. Robust studies on the physiology of human uterine contractions require in vitro models, utilizing a human source. Importantly, uterine contractility is a three-dimensionally (3D)-coordinated phenomenon and should be studied in a 3D environment. Here, we propose and assess for the first time a 3D in vitro model for the evaluation of human uterine contractility. Magnetic 3D bioprinting is applied to pattern human myometrium cells into rings, which are then monitored for contractility over time and as a function of various clinically relevant agents. Commercially available and patient-derived myometrium cells were magnetically bioprinted into rings in 384-well formats for throughput uterine contractility analysis. The bioprinted uterine rings from various cell origins and patients show different patterns of contractility and respond differently to clinically relevant uterine contractility inhibitors, indomethacin and nifedipine. We believe that the novel system will serve as a useful tool to evaluate the physiology of human parturition while enabling high-throughput testing of multiple agents and conditions.

  7. Free radicals in hypoxic rat diaphragm contractility: no role for xanthine oxidase.

    NARCIS (Netherlands)

    Heunks, L.M.A.; Machiels, H.A.; Abreu, R.A. de; Zhu, X.; Heijden, E. van der; Dekhuijzen, P.N.R.

    2001-01-01

    Recent evidence indicates that hypoxia enhances the generation of oxidants. Little is known about the role of free radicals in contractility of the rat diaphragm during hypoxia. We hypothesized that antioxidants improve contractility of the hypoxic rat diaphragm and that xanthine oxidase (XO) is an

  8. Effects of lengthening contraction on calcium kinetics and skeletal muscle contractility in humans

    DEFF Research Database (Denmark)

    Nielsen, J S; Madsen, K; Jørgensen, L V

    2005-01-01

    We have tested the hypothesis that the altered muscle contractility after lengthening contractions (LC) is caused by altered calcium (Ca2+) kinetics.......We have tested the hypothesis that the altered muscle contractility after lengthening contractions (LC) is caused by altered calcium (Ca2+) kinetics....

  9. Contractility of the guinea pig bladder measured in situ and in vitro

    NARCIS (Netherlands)

    J.M. Groen (Jan); R. van Mastrigt (Ron); J.L.H.R. Bosch (Ruud)

    1994-01-01

    textabstractTo study the relative importance of neurogenic factors in detrusor contractility and to relate a total bladder in vitro contractility model to a previously described bladder wall strip model, active intravesical pressure values were compared in situ and in vitro in eight male guinea

  10. Arterial stick

    Science.gov (United States)

    ... to breathing problems or problems with the body's metabolism . Sometimes arterial sticks are done to get blood ... and the A.D.A.M. Editorial team. Bacterial Infections Read more Blood Read more Blood Disorders ...

  11. Hepatic artery resistive index (HARI) and non-alcoholic fatty liver disease (NAFLD) fibrosis score in NAFLD patients: cut-off suggestive of non-alcoholic steatohepatitis (NASH) evolution.

    Science.gov (United States)

    Tana, Claudio; Tana, Marco; Rossi, Stefano; Silingardi, Mauro; Schiavone, Cosima

    2016-09-01

    Conventional ultrasound (US) is reliable to reveal the presence of non-alcoholic fatty liver disease (NAFLD), but it is neither sensitive nor specific to reveal fibrosis clues, except in advanced stages where signs of cirrhosis are evident. NALFD fibrosis score is a non-invasive parameter that predicts well the presence of significant fibrosis, but correlations with US parameters are lacking. The aim of this study was, therefore, to compare resistive index of hepatic artery (HARI) of NAFLD patients with different severity degrees of diffuse fatty liver disease vs HARI of controls, and to compare HARI of NAFLD patients with different NAFLD fibrosis scores vs HARI of controls. This was a spontaneous, no-profit observational study conducted in our US department between December 2013 and July 2014. Patients with NAFLD with different severity of disease and healthy controls were included. Echogenicity and size of liver and spleen, maximum portal vein velocity, RI, peak systolic velocity (PSV), and end diastolic velocity (EDV) of splenic artery, PSV, EDV, and RI of hepatic artery, and NAFLD fibrosis score were acquired and compared between groups. HARI was significantly lower in NAFLD patients than controls (p steatosis, might suggest the execution of biopsy to predict the risk of progression to steatohepatitis and fibrous tissue accumulation. Low values of HARI may be expression of lower risk, which does not necessitate any biopsy.

  12. The benefit of enhanced contractility in the infarct borderzone: A virtual experiment.

    Directory of Open Access Journals (Sweden)

    Zhihong eZhang

    2012-04-01

    Full Text Available A. Objectives Contractile function in the normally perfused infarct borderzone (BZ is depressed. However, the impact of reduced BZ contractility on left ventricular (LV pump function is unknown. As a consequence, there have been no therapies specifically designed to improve BZ contractility. We tested the hypothesis that an improvement in borderzone contractility will improve LV pump function.B. Methods From a previously reported study, magnetic resonance (MRI images with non-invasive tags were used to calculate 3D myocardial strain in five sheep 16 weeks after anteroapical myocardial infarction. Animal specific finite element (FE models were created using MRI data and LV pressure obtained at early diastolic filling. Analysis of borderzone function using those FE models has been previously reported. Chamber stiffness, pump function (Starling’s law and stress in the fiber, cross fiber and circumferential directions were calculated. Animal-specific FE models were performed for three cases: a impaired BZ contractility (INJURED; b BZ contractility fully restored (100% BZ IMPROVEMENT; or c BZ contractility partially restored (50% BZ IMPROVEMENT.C. Results 100% BZ IMPROVEMENT and 50% BZ IMPROVEMENT both caused an upward shift in the Starling relationship, resulting in a large (36% and 26% increase in stroke volume at LVPED = 20 mm Hg (8.0 ml, p<0.001. Moreover, there were a leftward shift in the end systolic pressure volume relationship, resulting in a 7% and 5% increase in LVPES at 110 mm Hg (7.7 ml, p<0.005. It showed that even 50% BZ IMPROVEMENT was sufficient to drive much of the calculated increase in function. D. Conclusions. Improved borderzone contractility has a beneficial effect on LV pump function. Partial improvement of borderzone contractility was sufficient to drive much of the calculated increase in function. Therapies specifically designed to improve borderzone contractility should be developed.

  13. Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

    Directory of Open Access Journals (Sweden)

    Ravi Goyal

    Full Text Available In response to hypoxia and other stress, the sympathetic (adrenergic nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1 - adrenergic receptor (AR subtypes (α1A-, α1B-, and α1D-AR. Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH, contractility of middle cerebral arteries (MCA is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m and those exposed to LTH (110 days at 3801 m. Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05 in the maximum tension achieved by 10-5 M phenylephrine (PHE. LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05 inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05 α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

  14. Cardiac contractility, central haemodynamics and blood pressure regulation during semistarvation

    DEFF Research Database (Denmark)

    Stokholm, K H; Breum, L; Astrup, A

    1991-01-01

    and equilibrium technique by [99Tcm]red blood cells). Cardiac output decreased concomitantly with the reduction in oxygen uptake as the calculated systemic arteriovenous difference of oxygen was unaltered. There were no significant decreases in left ventricular contractility indices, i.e. the ejection fraction......Eight obese patients were studied before and after 2 weeks of treatment by a very-low-calorie diet (VLCD). Cardiac output and central blood volume (pulmonary blood volume and left atrial volume) were determined by indicator dilution (125I-albumin) and radionuclide angiocardiography (first pass......, the peak ejection rate and changes in end-systolic volume. Also the diastolic function evaluated by the peak filling rate remained normal. Furthermore, no sign of backward failure could be demonstrated since the central blood volume was not significantly increased. Both systolic and diastolic blood...

  15. Contractile reaction of isolated frog aorta after X-irradiation

    International Nuclear Information System (INIS)

    Michailov, M.C.; Prechter, I.; Greimel, H.; Welscher, U.E.

    1983-01-01

    The action of X-rays (50 kV, filtered by 0.3 mm Al) on helical strip of frog aorta (rana esculenta) has been investigated. The isolated preparations have a stable basal tone and are radio-sensitive to X-rays which induce reversible, dose-dependent, contractile responses. After repeated irradiational tachyphylaxis appears. The threshold doses are about 250 R at 3 to 6 kR/min, antiadrenergic (phentolamine, propranolol), anticholinergic (atropin), antihistaminic (Neo-Bridal) and serotoninergic (Deseril) drugs have no visible influence on the X-ray induced reaction, i.e. these action mechanisms of the irradiation-induced contraction do not seem probable. Theophylline and cAMP inhibit the X-ray contraction probably non-specifically. Indometacin also inhibits the X-ray contraction: this suggests participation of prostaglandin-mechanism on the contraction of frog aorta after irradiation. (orig.) [de

  16. Intensidades de treinamento resistido e pressão arterial de idosas hipertensas - um estudo piloto Resistance training intensities and blood pressure of hypertensive older women - a pilot study

    Directory of Open Access Journals (Sweden)

    Eline Silva da Cunha

    2012-12-01

    Full Text Available INTRODUÇÃO: Observa-se que a literatura apresenta uma lacuna acerca da intensidade ideal de treinamento resistido para idosos hipertensos, os poucos estudos existentes utilizam treinamentos com diferentes intensidades. OBJETIVO: Verificar o efeito de duas intensidades de treinamento resistido sobre a pressão arterial de idosas hipertensas controladas. Métodos: Dezesseis idosas hipertensas, controladas por medicação anti-hipertensiva, foram divididas em dois grupos através de sorteio. Nove pacientes foram submetidas a treinamento resistido moderado (G1 e sete, a treinamento resistido leve (G2. As pacientes realizaram oito semanas de treinamento resistido, com frequência de três vezes por semana em dias alternados, no período vespertino. Os exercícios realizados foram respectivamente: leg press, supino reto, extensão de joelhos, puxada frontal, flexão de joelhos, abdução de ombro, abdução unilateral de quadril com cross over e rosca direta com barra. RESULTADOS: As pacientes do G1 apresentaram redução tanto nos valores de repouso da pressão arterial diastólica (PAD p BACKGROUND: The optimum intensity of resistance training for hypertensive elderly has not been studied yet and the few studies in the literature used training with distinct intensities. Objective: To verify the effect of two resistance training intensities on blood pressure (BP of elderly women with controlled hypertension. METHODS: Sixteen older women with hypertension controlled by anti-hypertensive drug were randomly divided into two groups. Nine patients were submitted to moderate resistance training (G1 and seven patients were submitted to mild resistance training (G2. The patients underwent eight weeks of resistance training, with frequency of three times per week on alternate days in the afternoon. The exercises performed were: leg press, bench press, knee extension, lat pull-down, knee flexion, shoulder abduction, standing cable hip abduction and biceps

  17. Redox regulation in skeletal muscle during contractile activity and aging.

    Science.gov (United States)

    Palomero, J; Jackson, M J

    2010-04-01

    Skeletal muscle has the ability to adapt and remodel after functional, mechanical, and metabolic stresses by activation of different adaptation mechanisms that induce gene expression, biochemical changes, and structural remodeling. Skeletal muscle cells continuously generate reactive oxygen and nitrogen species (RONS), which can act as mediators in cellular signaling pathways that regulate the adaptation mechanisms. There is strong evidence that indicates that RONS are generated in skeletal muscle cells during contractile activity and this induces the activation of transcription factors which modulate gene expression of antioxidant and protective proteins. Thus, it has been proposed that RONS act as signals that modulate the adaptation mechanisms in skeletal muscle and other cells. Structural and functional changes occur in skeletal muscle during aging and are characterized by a reduction of muscle mass and force (sarcopenia). The causes are known, however, there is considerable support for an involvement of RONS in the process of aging and sarcopenia. Several studies indicate that adaptive responses of skeletal muscle that are activated and regulated by RONS are disrupted during aging. This reduction of skeletal muscle adaptation to contractile activity during aging might be responsible for the loss of muscle mass and function and the progressive deterioration of this organ. In summary, there is sufficient evidence that indicates that cellular redox regulation in skeletal muscle is crucial in the physiology and pathology of skeletal muscle. However, new methodologies and experimental models are required for understanding the complex biology of RONS in the cell. This will provide future interventions that mitigate pathologies and aging of skeletal muscle.

  18. Effects of resistance training combined with moderate-intensity endurance or low-volume high-intensity interval exercise on cardiovascular risk factors in patients with coronary artery disease.

    Science.gov (United States)

    Currie, Katharine D; Bailey, Kaitlyn J; Jung, Mary E; McKelvie, Robert S; MacDonald, Maureen J

    2015-11-01

    To determine the effects of resistance training combined with either moderate-intensity endurance or low-volume high-intensity interval training on cardiovascular risk profiles in patients with coronary artery disease. Factorial repeated-measures study design. Nineteen patients were randomized into moderate-intensity endurance (n = 10) or high-intensity interval (n = 9) groups, and attended 2 supervised exercise sessions a week for 6-months. The first 3-months involved exclusive moderate-intensity endurance or high-intensity interval exercise, after which progressive resistance training was added to both groups for the remaining 3-months. Fitness (VO(2)peak), blood pressure and heart rate, lipid profiles and health related quality of life assessments were performed at pretraining, 3 and 6-months training. VO(2)peak increased from pretraining to 3-months in both groups (moderate-intensity endurance: 19.8 ± 7.3 vs. 23.2 ± 7.4 ml kg(-1)min(-1); high-intensity interval: 21.1 ± 3.3 vs. 26.4 ± 5.2 ml kg(-1)min(-1), pexercise, while all remaining indices were unchanged. Low-volume high-intensity interval exercise did not elicit improvements in lipids or health related quality of life. Blood pressures and heart rates were unchanged with training in both groups. Findings from our pilot study suggest improvements in fitness occur within the first few months of training in patients with coronary artery disease, after which the addition of resistance training to moderate-intensity endurance and high-intensity interval exercise elicited no further improvements. Given the importance of resistance training in cardiac rehabilitation, additional research is required to determine its effectiveness when combined with high-intensity interval exercise. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  19. Calcium-induced contraction and contractile protein of gallbladder smooth muscle after high-cholesterol feeding of prairie dogs

    NARCIS (Netherlands)

    Li, Y. F.; Weisbrodt, N. W.; Moody, F. G.; Coelho, J. C.; Gouma, D. J.

    1987-01-01

    Feeding a high-cholesterol diet to prairie dogs causes a reduction in contractile responses of gallbladder smooth muscle from these animals. In this study, the influence of cholesterol feeding on the contractile response to calcium and on the concentration of the contractile proteins actin and

  20. Redução da pressão arterial e do duplo produto de repouso após treinamento resistido em idosas hipertensas Reduction of arterial pressure and double product at rest after resistance exercise training in elderly hypertensive women

    Directory of Open Access Journals (Sweden)

    Denize Faria Terra

    2008-11-01

    Full Text Available FUNDAMENTO: Em razão das controvérsias existentes na literatura quanto aos possíveis benefícios do treinamento resistido (TR sobre a pressão arterial de repouso (PA e por causa da escassez de estudos com indivíduos idosos e hipertensos, o TR é pouco recomendado como forma de tratamento não-farmacológico da hipertensão arterial. OBJETIVO: Verificar os efeitos do TR progressivo sobre a pressão arterial de repouso (PA, a freqüência cardíaca (FC e o duplo produto (DP em idosas hipertensas controladas. MÉTODOS: Vinte mulheres idosas (66,8 ± 5,6 anos de idade sedentárias, controladas com medicação anti-hipertensiva, realizaram 12 semanas de TR, compondo o grupo do treinamento resistido (GTR. Vinte e seis idosas (65,3 ± 3,4 anos de idade hipertensas controladas não realizaram exercícios físicos durante a pesquisa, constituindo o grupo-controle. RESULTADOS: Houve redução significativa nos valores de repouso da pressão arterial sistólica (PAS, da pressão arterial média (PAM e do DP após o TR. Não foram encontradas reduções significativas na pressão arterial diastólica (PAD e na FC de repouso após o TR em ambos os grupos. A magnitude da queda no GTR foi de 10,5 mmHg, 6,2 mmHg e 2.218,6 mmHg x bpm para a PAS, PAM e o DP, respectivamente. CONCLUSÃO: O TR progressivo reduziu a PAS, PAM e o DP de repouso de idosas hipertensas, controladas com medicação anti-hipertensiva.BACKGROUND: Due to the existing controversies in literature about the potential benefits of resistance exercise training (RT on arterial blood pressure (BP at rest, and the lack of studies conducted with elderly hypertensive individuals, RT is seldom recommended as a non-pharmacological treatment for arterial hypertension. OBJECTIVE: To verify the effect of progressive RT on BP, HR, and RPP in elderly women with controlled hypertension. METHODS: 20 elderly women (66.8 ± 5.6 years of age, with a sedentary lifestyle, monitored with anti

  1. Arterial stiffness

    Directory of Open Access Journals (Sweden)

    Ursula Quinn

    2012-09-01

    Full Text Available Measurements of biomechanical properties of arteries have become an important surrogate outcome used in epidemiological and interventional cardiovascular research. Structural and functional differences of vessels in the arterial tree result in a dampening of pulsatility and smoothing of blood flow as it progresses to capillary level. A loss of arterial elastic properties results a range of linked pathophysiological changes within the circulation including increased pulse pressure, left ventricular hypertrophy, subendocardial ischaemia, vessel endothelial dysfunction and cardiac fibrosis. With increased arterial stiffness, the microvasculature of brain and kidneys are exposed to wider pressure fluctuations and may lead to increased risk of stroke and renal failure. Stiffening of the aorta, as measured by the gold-standard technique of aortic Pulse Wave Velocity (aPWV, is independently associated with adverse cardiovascular outcomes across many different patient groups and in the general population. Therefore, use of aPWV has been proposed for early detection of vascular damage and individual cardiovascular risk evaluation and it seems certain that measurement of arterial stiffness will become increasingly important in future clinical care. In this review we will consider some of the pathophysiological processes that result from arterial stiffening, how it is measured and factors that may drive it as well as potential avenues for therapy. In the face of an ageing population where mortality from atheromatous cardiovascular disease is falling, pathology associated with arterial stiffening will assume ever greater importance. Therefore, understanding these concepts for all clinicians involved in care of patients with cardiovascular disease will become vital.

  2. Broad-range TRP channel inhibitors (2-APB, flufenamic acid, SKF-96365) affect differently contraction of resistance and conduit femoral arteries of rat

    Czech Academy of Sciences Publication Activity Database

    Bencze, Michal; Behuliak, Michal; Vavřínová, Anna; Zicha, Josef

    2015-01-01

    Roč. 765, Oct 15 (2015), s. 533-540 ISSN 0014-2999 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : femoral artery * TRP channel * 2-APB * flufenamic acid * SKF-96365 * vascular contraction Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.730, year: 2015

  3. Carotid artery surgery

    Science.gov (United States)

    Carotid endarterectomy; CAS surgery; Carotid artery stenosis - surgery; Endarterectomy - carotid artery ... through the catheter around the blocked area during surgery. Your carotid artery is opened. The surgeon removes ...

  4. Role of Rho-associated protein kinase in tone and calcium sensitivity of cannulated rat mesenteric small arteries

    NARCIS (Netherlands)

    VanBavel, E.; van der Meulen, E. T.; Spaan, J. A.

    2001-01-01

    The regulation of vascular tone includes modulation of contractile element calcium sensitivity. We tested the involvement of the Rho-associated protein kinase p160ROCK in tone and calcium sensitivity of cannulated rat mesenteric small arteries. These vessels developed basal tone and showed myogenic

  5. Role of protein kinase C in myogenic calcium-contraction coupling of rat cannulated mesenteric small arteries

    NARCIS (Netherlands)

    Wesselman, J. P.; Spaan, J. A.; van der Meulen, E. T.; VanBavel, E.

    2001-01-01

    1. The present study was designed to determine the role of protein kinase C (PKC) in the myogenic response of small arteries. In particular, we tested whether inhibition of PKC reverses the previously found pressure-induced elevation of contractile element calcium sensitivity. 2. Rat mesenteric

  6. Peritubular Contractile Cells in Testis and Epididymis of the Dog, Canis lupus familiaris

    Directory of Open Access Journals (Sweden)

    Gunter F. Egger

    2009-01-01

    Full Text Available Contractile cells surrounding the tubular system of the mammalian testis and epididymis are supposed to contribute to the initial transport of spermatozoa from the testis to epididymis. Testicular peritubular smooth muscle cells have been characterised in detail especially in rodents and humans. The aim of our study was to assess the distribution of peritubular contractile cells of the canine tubuli seminiferi, rete testis channels, ductuli efferentes, and ductus epididymidis by immunohistochemistry and transmission electron microscopy and to classify these cells with respect to their possible physiological function. The entire tubular system of the canine testis and epididymis is surrounded by contractile cells expressing smooth muscle actin, smooth muscle myosin and desmin, which are enveloped, at least partly, by a basal lamina. Some contractile cells of the tubuli seminiferi, rete channels, and efferent ducts and sometimes also single peritubular cells of the ductus epididymidis express vimentin. Contractile cells of seminiferous tubules and efferent ducts represent an intermediate cell type exhibiting characteristics of both smooth muscle cells (SMC and myofibroblasts, those of rete channels stellate myofibroblasts, and those of the ductus epididymidis SMC. Differences in structure and arrangement of the contractile cells between seminiferous tubules, rete channels, efferent ducts, and ductus epididymidis suggest different functions. Myofibroblasts and contractile cells similar to them could be mainly responsible for the maintenance of an appropriate tissue turgor, whereas contraction of SMC of the ductus epididymidis might cause propulsion of spermatozoa by peristaltic waves.

  7. Jackhammer esophagus: Assessing the balance between prepeak and postpeak contractile integral.

    Science.gov (United States)

    Xiao, Y; Carlson, D A; Lin, Z; Alhalel, N; Pandolfino, J E

    2017-11-29

    We hypothesized that symptoms in Jackhammer esophagus (JH) are associated with an imbalance between the prepeak and postpeak phases of contraction. Thus, we developed a method to distinguish the contractile integral components of prepeak and postpeak phase contractile activity to determine the contribution of each phase and their association with dysphagia. Patients diagnosed with JH were enrolled and compared to controls. The first five intact swallows during manometry were analyzed. A single swallow was divided into a prepeak and postpeak phase. The contractile integral of each phase and its corresponding time-controlled integral were computed. All metrics were compared between controls and JH patients subcategorized by the impaction dysphagia question (IDQ) score with cut-off of 6. Thirty eight JH patients and 71 controls were included. Twelve JH patients had IDQ ≤ 6 and 26 with IDQ > 6. JH patients had higher contractile integral in both phases, and a higher ratio between postpeak to prepeak contractile integral independent of duration. Similarly, JH patients with an IDQ > 6 had higher contractile metrics than those with IDQ ≤ 6. There was a correlation between the IDQ score and the ratio within the postpeak to prepeak contractile integral (r = .375). Abnormalities in contractile integral of the postpeak phase are more significant in JH with higher dysphagia scores Although the total postpeak contractile integral was higher in symptomatic patients, this was associated with longer duration of postpeak activity suggesting that dysphagia patients with JH have a defect in the postpeak phase of peristalsis. © 2017 John Wiley & Sons Ltd.

  8. Vascular smooth cell proliferation in perfusion culture of porcine carotid arteries

    International Nuclear Information System (INIS)

    Liao, Dan; Lin, Peter H.; Yao Qizhi; Chen Changyi

    2008-01-01

    Objective of this study was to develop a novel in vitro artery culture system to study vascular smooth muscle cell (SMC) proliferation of porcine carotid arteries in response to injury, basic fibroblast growth factor (FGF2), and FGF2 conjugated with cytotoxin saporin (SAP). Perfusion-cultured porcine carotid arteries remained contractile in response to norepinephrine and relaxant to acetylcholine for up to 96 h. SMC proliferation of cultured arteries was detected by bromodeoxyuridine incorporation in both non-injured and balloon-injured arteries. In the inner layer of the vessel wall near the lumen, SMC proliferation were less than 10% in uninjured vessels, 66% in injured vessels, 80% in injured vessels with FGF2 treatment, and 5% in injured vessels with treatment of FGF2-SAP. Thus, the cultured porcine carotid arteries were viable; and the injury stimulated SMC proliferation, which was significantly enhanced by FGF2 and inhibited by FGF2-SAP

  9. Catecholamines and myocardial contractile function during hypodynamia and with an altered thyroid hormone balance

    Science.gov (United States)

    Pruss, G. M.; Kuznetsov, V. I.; Zhilinskaya, A. A.

    1980-01-01

    The dynamics of catecholamine content and myocardial contractile function during hypodynamia were studied in 109 white rats whose motor activity was severely restricted for up to 30 days. During the first five days myocardial catecholamine content, contractile function, and physical load tolerance decreased. Small doses of thyroidin counteracted this tendency. After 15 days, noradrenalin content and other indices approached normal levels and, after 30 days, were the same as control levels, although cardiac functional reserve was decreased. Thyroidin administration after 15 days had no noticeable effect. A detailed table shows changes in 17 indices of myocardial contractile function during hypodynamia.

  10. Controlled chaos: three-dimensional kinematics, fiber histochemistry, and muscle contractile dynamics of autotomized lizard tails.

    Science.gov (United States)

    Higham, Timothy E; Lipsett, Kathryn R; Syme, Douglas A; Russell, Anthony P

    2013-01-01

    greater resistance to fatigue, followed by the regenerate tail and then the fast iliofibularis fibers. These results suggest that the relatively slow and oxidative fibers found within the tail musculature have a significant impact on contractile function, which translates into a trade-off between longevity of performance and power after autotomy.

  11. Short-term incubation of equine laminar veins with cortisol and insulin alters contractility in vitro: possible implications for the pathogenesis of equine laminitis.

    Science.gov (United States)

    Keen, J A; McGorum, B C; Hillier, C; Nally, J E

    2013-08-01

    This study investigated the effects of cortisol and insulin, hormones that affect both glycaemic status and vascular function, on the in vitro contractility of isolated healthy equine small laminar veins. Small veins (150-500 μm) draining the digital laminae from healthy horses or ponies were investigated by wire myography. Concentration response curves were constructed for noradrenaline (NA), phenylephrine (PE), endothelin-1 (ET-1) and 5-hydroxytryptamine (5-HT) in the presence of either cortisol (10(-6 ) m) or insulin (1000 μIU/mL). Cortisol significantly increased the maximum contractility of laminar veins to the vasoconstrictors NA and 5-HT but decreased the maximal contraction to ET-1. Insulin decreased the contractility of vessels to PE and ET-1. It is possible that short-term cortisol excess could enhance venoconstrictor responses to 5-HT and NA in laminar veins in vivo, thereby predisposing to laminitis. Additionally, a reduction in the ability of insulin to counteract alpha-adrenoreceptor and ET-1-mediated contraction, likely to occur in subjects with insulin resistance, may further exacerbate venoconstriction in animals prone to laminitis. These mechanisms may also predispose horses with disorders such as equine Cushing's disease and equine metabolic syndrome to laminitis. © 2012 John Wiley & Sons Ltd.

  12. Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries.

    Directory of Open Access Journals (Sweden)

    Hilda Ahnstedt

    Full Text Available BACKGROUND AND PURPOSE: Male-female differences may significantly impact stroke prevention and treatment in men and women, however underlying mechanisms for sexual dimorphism in stroke are not understood. We previously found in males that cerebral ischemia upregulates contractile receptors in cerebral arteries, which is associated with lower blood flow. The present study investigates if cerebral arteries from men and women differ in cerebrovascular receptor upregulation. EXPERIMENTAL APPROACH: Freshly obtained human cerebral arteries were placed in organ culture, an established model for studying receptor upregulation. 5-hydroxtryptamine type 1B (5-HT1B, angiotensin II type 1 (AT1 and endothelin-1 type A and B (ETA and ETB receptors were evaluated using wire myograph for contractile responses, real-time PCR for mRNA and immunohistochemistry for receptor expression. KEY RESULTS: Vascular sensitivity to angiotensin II and endothelin-1 was markedly lower in cultured cerebral arteries from women as compared to men. ETB receptor-mediated contraction occurred in male but not female arteries. Interestingly, there were similar upregulation in mRNA and expression of 5-HT1B, AT1, and ETB receptors and in local expression of Ang II after organ culture. CONCLUSIONS AND IMPLICATIONS: In spite of receptor upregulation after organ culture in both sexes, cerebral arteries from women were significantly less responsive to vasoconstrictors angiotensin II and endothelin-1 as compared to arteries from men. This suggests receptor coupling and/or signal transduction mechanisms involved in cerebrovascular contractility may be suppressed in females. This is the first study to demonstrate sex differences in the vascular function of human brain arteries.

  13. Umbilical artery tone in maternal obesity

    Directory of Open Access Journals (Sweden)

    Glavey Siobhan V

    2009-01-01

    Full Text Available Abstract Background The increasing prevalence of obesity constitutes a major health problem in obstetrics with implications for feto-maternal growth and wellbeing. This study investigated and compared the contractile properties of umbilical arteries excised from obese women, with those excised from women with a normal body mass index (BMI. Methods Sections of umbilical artery were obtained from umbilical cord samples immediately after delivery and mounted for isometric recording in organ tissue baths under physiological conditions. Cumulative additions of 5-Hydroxytryptamine (5-HT and Prostaglandin F-2alpha (PgF2alpha were added in the concentration range of 1 nmol/L to 10 micromol/L. Control vessels were exposed to Krebs physiological salt solution (PSS only. The resultant effects of each drug addition were measured using the Powerlab hardware unit. Results 5-HT exerted a significant effect on human umbilical artery tone at concentrations of 100 nmol/L, 1 micromol/L, and 10 micromol/L in normal (n = 5; P 0.05. Conclusion These findings support the hypothesis that endogenous regulation of umbilical artery tone is altered in association with maternal obesity. This may be linked to the cardiovascular effects of secretory products of adipose tissue, with implications for the feto-maternal circulation.

  14. Effect of training on contractile and metabolic properties of wrist extensors in spinal cord-injured individuals

    DEFF Research Database (Denmark)

    Hartkopp, Andreas; Harridge, Stephen D R; Mizuno, Masao

    2003-01-01

    Paretic human muscle rapidly loses strength and oxidative endurance, and electrical stimulation training may partly reverse this. We evaluated the effects of two training protocols on the contractile and metabolic properties of the wrist extensor in 12 C-5/6 tetraplegic individuals. The wrist...... by (31)P nuclear magnetic resonance spectroscopy ((31)P-NMRS) during and following a continuous 40-s 10-HZ contraction. In the Hr group the cost of contraction decreased by 38% (P ... induced stimulation of the wrist extensor muscles in spinal cord injury (SCI) increases fatigue resistance independent of training pattern. However, only the Hr protocol increased muscle strength and was shown to improve muscle aerobic metabolism after training. Muscle Nerve 27: 72-80, 2003...

  15. Contractility, differential tension and membrane removal lead zebrafish epiboly biomechanics.

    Science.gov (United States)

    Marsal, Maria; Hernández-Vega, Amayra; Martin-Blanco, Enrique

    2017-07-18

    Precise tissue remodeling during development is essential for shaping embryos and optimal organ function. Epiboly is an early gastrulation event by which the blastoderm expands around the yolk to engulf it. Three different layers are involved in this process, an epithelial layer (the enveloping layer, EVL), the embryo proper, constituted by the deep cells (DCs), and the yolk cell. Although teleost epiboly has been studied for many years, a clear understanding of its mechanics was still missing. Here we present new information on the cellular, molecular and mechanical elements involved in epiboly that, together with some other recent data and upon comparison with previous biomechanical models, lets conclude that the expansion of the epithelia is passive and driven by active cortical contraction and membrane removal in the adjacent layer, the External Yolk Syncytial Layer (E-YSL). The isotropic actomyosin contraction of the E-YSL cortex generates an anisotropic stress pattern and a directional net movement consequence of the differences in the deformation response of the 2 opposites adjacent domains (EVL and the Yolk Cytoplasmic Layer - YCL). Contractility is accompanied by the local formation of membrane folds and its removal by Rab5ab dependent macropinocytosis. The increase in area of the epithelia during the expansion is achieved by cell-shape changes (flattening) responding to spherical geometrical cues. The counterbalance between the geometry of the embryo and forces dissipation among different elements is therefore essential for epiboly global coordination.

  16. Mechanism of action of ethanol on heart contractility

    International Nuclear Information System (INIS)

    Oquendo-Muriente, I.; De Mello, W.C.

    1986-01-01

    Ethanol depresses heart contractility. To investigate the mechanism of the negative inotropic action of ethanol, rat ventricular strips were dissected and mounted vertically in a transparent chamber. The preparation was superfused initially with normal oxygenated Tyrode solution (32.5 0 C) and electrically stimulated (1 Hz). After 1 hour of equilibration, contractures were elicited by exposing the muscle strips to high K + (100 mM) solution. Studies on the influence of (Ca 2+ ) 0 on K + contractures showed that the first rapid component of the contracture (58 mg/sec - S.E. +/- 8; n = 8) was greatly dependent upon (Ca 2+ ) 0 while the second slow component (20 mg/sec - S.E. +/- 5; n = 8) was slightly altered. The addition of ethanol (400 mg/100 ml) to high K solution abolished the fast component and reduced the amplitude of the second phase of K contractures. Similar results were obtained with verapamil (10 -5 M). These results, as well as studies on the effect of the drug on 45 Ca fluxes support the view that ethanol decreases the permeability of the heart cell membrane to Ca

  17. Mechanism of action of ethanol on heart contractility

    Energy Technology Data Exchange (ETDEWEB)

    Oquendo-Muriente, I.; De Mello, W.C.

    1986-03-05

    Ethanol depresses heart contractility. To investigate the mechanism of the negative inotropic action of ethanol, rat ventricular strips were dissected and mounted vertically in a transparent chamber. The preparation was superfused initially with normal oxygenated Tyrode solution (32.5/sup 0/C) and electrically stimulated (1 Hz). After 1 hour of equilibration, contractures were elicited by exposing the muscle strips to high K/sup +/ (100 mM) solution. Studies on the influence of (Ca/sup 2 +/)/sub 0/ on K/sup +/ contractures showed that the first rapid component of the contracture (58 mg/sec - S.E. +/- 8; n = 8) was greatly dependent upon (Ca/sup 2 +/)/sub 0/ while the second slow component (20 mg/sec - S.E. +/- 5; n = 8) was slightly altered. The addition of ethanol (400 mg/100 ml) to high K solution abolished the fast component and reduced the amplitude of the second phase of K contractures. Similar results were obtained with verapamil (10/sup -5/ M). These results, as well as studies on the effect of the drug on /sup 45/Ca fluxes support the view that ethanol decreases the permeability of the heart cell membrane to Ca.

  18. Deactivation rate and shortening velocity as determinants of contractile frequency.

    Science.gov (United States)

    Marsh, R L

    1990-08-01

    The kinetic properties of muscle that could influence locomotor frequency include rate of activation, rate of cross-bridge "attachment", intrinsic shortening velocity, and rate of deactivation. The latter two mechanisms are examined using examples from high-speed running in lizards and escape swimming in scallops. During running, inertial loading and elastic energy storage probably mitigate the effects of thermal alterations in intrinsic muscle shortening velocity. The result is a rather low thermal dependence of stride frequency over a 15-20 degree C temperature range. However, at lower temperatures, the longer times required for deactivation cause the thermal dependence of frequency to increase greatly. Scallops use a single muscle to swim by jet propulsion. In vivo shortening velocity in these animals also shows a low thermal dependence. As with high-speed running, the mechanics of jet propulsion may limit the effects of thermally induced changes in intrinsic shortening velocity. The largest thermal effect during swimming is on the initial phase of valve opening. The effects of temperature on the rate of deactivation of the adductor muscle could play an important role in limiting reextension of the muscle, which is dependent on elastic energy storage in the hinge ligament. These examples illustrate that the relative importance of various intrinsic contractile properties in controlling locomotor performance depends on the mechanics of the movements.

  19. Reduced calcium responsiveness characterizes contractile dysfunction following coronary microembolization.

    Science.gov (United States)

    Skyschally, Andreas; Gres, Petra; van Caster, Patrick; van de Sand, Anita; Boengler, Kerstin; Schulz, Rainer; Heusch, Gerd

    2008-11-01

    We addressed calcium responsiveness in microembolized myocardium at 6 h after coronary microembolization (ME). In anesthetized pigs calcium responsiveness was determined as the increase of a myocardial work index (WI; LV pressure development vs. wall thickening) in response to a graded intracoronary infusion of CaCl(2) at baseline and at 6 h after ME or placebo, respectively. At baseline, CaCl(2 )infusion increased WI in both groups (ME: 296 +/- 22 to 468 +/- 47 mmHg*mm; placebo: 324 +/- 24 to 485 +/- 38 mmHg*mm; mean +/- SEM). At 6 h after ME, WI was decreased by 159 +/- 16 mmHg*mm (P < 0.05 vs. baseline) and remained reduced at any calcium concentration, whereas it was unchanged with placebo. The calcium concentration in coronary blood necessary to achieve the half maximal increase in WI remained unchanged from baseline to 6 h and did not differ between placebo and ME. The ME-induced myocardial dysfunction is not related to an altered calcium sensitivity, but is characterized by a reduced maximal contractile force.

  20. The contractility of elongated microvilli in early sea urchin embryos.

    Science.gov (United States)

    Spiegel, Evelyn; Howard, Louisa; Spiegel, Melvin

    1990-04-01

    Elongated microvilli attach the early sea urchin embryo to the fertilization envelope and support it in a concentric position within the perivitelline space. The contractility of the elongated microvilli was demonstrated in several ways. (1) During normal cleavage, these microvilli change their length to adapt to the change in shape and numbers of blastomeres. (2) When treated with calcium-free sea water, embryos become eccentrically located and the microvilli extend further than normal on one side; when returned to normal sea water, the embryos become centered again. (3) Several agents cause the fertilization envelope to become higher and thinner than normal and the elongated microvilli to extend correspondingly if treated within ten min after fertilization. In some cases, both elongated microvilli and fertilization envelope return to normal size when returned to normal sea water. (4) Fertilization in a papain solution causes the elongated microvilli and the fertilization envelope to contract to the surface of the embryo. (5) Refertilization after the papain-induced contraction can bring about the elongation of these microvilli and the elevation of the fertilization envelope a second time. It was also shown that elongated microvilli are extended immediately upon fertilization, at the same time as the short microvilli. The firm adherence of the tips of elongated microvilli to the fertilization envelope by means of extracellular matrix fibers is shown in a high voltage electron microscope stereoimage. This allows us to understand why it is that when the elongated microvilli extend or contract, the fertilization envelope also extends and contracts accordingly.

  1. In vitro myometrial contractility reflects indication for caesarean section.

    Science.gov (United States)

    Quenby, S; Matthew, A; Zhang, J; Dawood, F; Wray, S

    2011-11-01

    To assess the extent to which in vitro measurements of myometrial contractility reflect the clinical indication for caesarean section. A prospective, observational hypothesis-generating study. Women were recruited from Liverpool Women's NHS Foundation Trust and experiments were performed in the Physiology Department at the University of Liverpool. Myometrial samples were taken from women undergoing a caesarean section during labour (n = 50) or from women having a repeat nonlabouring caesarean section (n = 70). The demographic characteristics of the women and indications for current and previous caesarean sections were recorded. The force, frequency and duration of spontaneous contractions of myometrial strips, and changes in the intracellular calcium concentration of the strips, were measured. Kruskall-Wallis and post hoc tests were used to assess the significance of differences between groups. Samples from women whose caesarean section was for fetal distress/acidosis (scalp pH force than those from women whose caesarean section was for delay in the first stage of labour (P force than did samples from women whose first caesarean section was for delay in the first stage of labour (P = 0.03). These findings suggest that the myometrium contracts with greater force in women who have a caesarean section for fetal distress. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

  2. Considerations for Contractile Electroactive Polymeric Materials and Actuators

    International Nuclear Information System (INIS)

    Rasmussen, L.; Erickson, Carl J.; Meixler, Lewis D.; Ascione, G.; Gentile, Charles A.; Tilson, C.; Bernasek, Stephen L.; Abelev, E.

    2009-01-01

    Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface

  3. Considerations for Contractile Electroactive Polymeric Materials and Actuators

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Lenore; Erickson, Carl J.; Meixler, Lewis D.; Ascione, George; Gentile, Charles A.; Tilson, Charles; Bernasek, Stephen L.; Abelev, Esta

    2009-06-16

    Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface.

  4. Mechanism of cytokinetic contractile ring constriction in fission yeast.

    Science.gov (United States)

    Stachowiak, Matthew R; Laplante, Caroline; Chin, Harvey F; Guirao, Boris; Karatekin, Erdem; Pollard, Thomas D; O'Shaughnessy, Ben

    2014-06-09

    Cytokinesis involves constriction of a contractile actomyosin ring. The mechanisms generating ring tension and setting the constriction rate remain unknown because the organization of the ring is poorly characterized, its tension was rarely measured, and constriction is coupled to other processes. To isolate ring mechanisms, we studied fission yeast protoplasts, in which constriction occurs without the cell wall. Exploiting the absence of cell wall and actin cortex, we measured ring tension and imaged ring organization, which was dynamic and disordered. Computer simulations based on the amounts and biochemical properties of the key proteins showed that they spontaneously self-organize into a tension-generating bundle. Together with rapid component turnover, the self-organization mechanism continuously reassembles and remodels the constricting ring. Ring constriction depended on cell shape, revealing that the ring operates close to conditions of isometric tension. Thus, the fission yeast ring sets its own tension, but other processes set the constriction rate. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Adipose-derived stem cells inhibit the contractile myofibroblast in Dupuytren's disease.

    NARCIS (Netherlands)

    Verhoekx, J.S.; Mudera, V.; Walbeehm, E.T.; Hovius, S.E.

    2013-01-01

    BACKGROUND: In an attempt to provide minimally invasive treatment for Dupuytren's disease, percutaneous disruption of the affected tissue followed by lipografting is being tested. Contractile myofibroblasts drive this fibroproliferative disorder, whereas stem cells have recently been implicated in

  6. High Intensity Exercise in Multiple Sclerosis: Effects on Muscle Contractile Characteristics and Exercise Capacity, a Randomised Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Inez Wens

    Full Text Available Low-to-moderate intensity exercise improves muscle contractile properties and endurance capacity in multiple sclerosis (MS. The impact of high intensity exercise remains unknown.Thirty-four MS patients were randomized into a sedentary control group (SED, n = 11 and 2 exercise groups that performed 12 weeks of a high intensity interval (HITR, n = 12 or high intensity continuous cardiovascular training (HCTR, n = 11, both in combination with resistance training. M.vastus lateralis fiber cross sectional area (CSA and proportion, knee-flexor/extensor strength, body composition, maximal endurance capacity and self-reported physical activity levels were assessed before and after 12 weeks.Compared to SED, 12 weeks of high intensity exercise increased mean fiber CSA (HITR: +21 ± 7%, HCTR: +23 ± 5%. Furthermore, fiber type I CSA increased in HCTR (+29 ± 6%, whereas type II (+23 ± 7% and IIa (+23 ± 6%, CSA increased in HITR. Muscle strength improved in HITR and HCTR (between +13 ± 7% and +45 ± 20% and body fat percentage tended to decrease (HITR: -3.9 ± 2.0% and HCTR: -2.5 ± 1.2%. Furthermore, endurance capacity (Wmax +21 ± 4%, time to exhaustion +24 ± 5%, VO2max +17 ± 5% and lean tissue mass (+1.4 ± 0.5% only increased in HITR. Finally self-reported physical activity levels increased 73 ± 19% and 86 ± 27% in HCTR and HITR, respectively.High intensity cardiovascular exercise combined with resistance training was safe, well tolerated and improved muscle contractile characteristics and endurance capacity in MS.ClinicalTrials.gov NCT01845896.

  7. Platelets as Contractile Nanomachines for Targeting Drug Delivery in Hemostasis and Thrombosis

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-13-1-0495 TITLE: Platelets as Contractile Nanomachines for Targeting Drug Delivery in Hemostasis and Thrombosis PRINCIPAL...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Platelets as Contractile Nanomachines for Targeting Drug Delivery in Hemostasis and Thrombosis 5b. GRANT...controlled nanocarriers as a novel and potentially paradigm-shifting strategy for targeted drug delivery to achieve hemostasis during bleeding. We have

  8. A study of ventricular contractility and other parameters possibly related to vasodepressor syncope

    Science.gov (United States)

    Hyatt, K. H.; Sullivan, R. W.; Spears, W. R.; Vetter, W. R.

    1973-01-01

    The effects of diminished orthostatic and exercise tolerance resulting from prolonged bedrest were studied by noninvasion methods to determine if alterations in myocardial contractility were induced by bedrest. These methods were apexcardiography, systolic time intervals, and echocardiography. It is concluded that bedrest causes detrimental alterations in the contractile state of the myocardium which accounts for the decreases in maximal oxygen uptaken during exercise after bedrest. Tabulated test data are included.

  9. Escherichia coli-mediated impairment of ureteric contractility is uropathogenic E. coli specific.

    Science.gov (United States)

    Floyd, Rachel V; Upton, Mathew; Hultgren, Scott J; Wray, Susan; Burdyga, Theodor V; Winstanley, Craig

    2012-11-15

    Ureters are fundamental for keeping kidneys free from uropathogenic Escherichia coli (UPEC), but we have shown that 2 strains (J96 and 536) can subvert this role and reduce ureteric contractility. To determine whether this is (1) a widespread feature of UPEC, (2) exhibited only by UPEC, and (3) dependent upon type 1 fimbriae, we analyzed strains representing epidemiologically important multilocus sequence types ST131, ST73, and ST95 and non-UPEC E. coli. Contractility and calcium transients in intact rat ureters were compared between strains. Mannose and fim mutants were used to investigate the role of type 1 fimbriae. Non-UPEC had no significant effect on contractility, with a mean decrease after 8 hours of 8.8%, compared with 8.8% in controls. UPEC effects on contractility were strain specific, with decreases from 9.47% to 96.7%. Mannose inhibited the effects of the most potent strains (CFT073 and UTI89) but had variable effects among other UPEC strains. Mutation and complementation studies showed that the effects of the UTI89 cystitis isolate were fimH dependent. We find that (1) non-UPEC do not affect ureteric contractility, (2) impairment of contractility is a common feature of UPEC, and (3) the mechanism varies between strains, but for the most potent UPEC type 1 fimbriae are involved.

  10. A comparative study of contractility of the heart ventricle in some ectothermic vertebrates

    Directory of Open Access Journals (Sweden)

    Sergey Kharin

    2009-07-01

    Full Text Available The purpose of this study was to analyze contractility of the heart ventricle in selected reptilian and amphibian species having the same ventricular excitation pattern. Systolic time intervals and indices of contractility of the heart ventricle were measured in anaesthetized frogs, snakes, and tortoises by use of polycardiography. The electromechanical delay was significantly shorter in tortoises compared with the other two species. The isovolumetric contraction time in frogs was approximately twofold longer than in reptiles. The pre-ejection period was the longest in frogs and the shortest in tortoises, whereas snakes were intermediate. The ejection time was slightly longer in tortoises compared with the other two species. The greatest isovolumetric contraction index and the smallest myocardial tension index corresponded to the frog and tortoise heart ventricle, respectively. The intrasystolic index in tortoises was significantly greater than in frogs, whereas quite similar to that in snakes. The frog ventricle had lower contractility compared with the reptilian one. Although ventricular contractility tended to be lower in snakes compared with tortoises, this difference was not statistically significant. Possible causes for these differences are discussed. We suppose a large variety in ventricular contractility among amphibian and reptilian species having the same ventricular activation pattern. This variety may be conditioned by heart anatomy, intracardiac shunting, lifestyles, and habitats. It can only be hypothesized that on the average, ventricular contractility is higher in reptiles compared with amphibians and in chelonians compared with snakes.

  11. [The cardioprotective action of the anticonvulsant preparation sodium valproate in disorders of cardiac contractile function caused by acute myocardial infarct in rats].

    Science.gov (United States)

    Belkina, L M; Korchazhkina, N B; Kamskova, Iu G; Fomin, N A

    1997-01-01

    The preventive and therapeutical effects of sodium valproate (SV), 200 mg/kg, on cardiac contractile disorders (developed pressure, rate-pressure products, dp/dt) were studied in rats having 2-day myocardial infarction (MI). The postinfarction rather than preinfarction use of SV substantially restricted the depressed resting left ventricular function. Given by two regimens, SV increased cardiac resistance to the maximum isometric load induced by 60-sec ligation of the ascending aorta. The cardioprotective effect of the drug was shown due to its positive chronotropic action rather than its inotropic one. Thus, SV may be used as an effective drug for the prevention and treatment of postinfarct cardiac dysfunctions.

  12. Endothelin-1 shifts the mediator of bradykinin-induced relaxation from NO to H2 O2 in resistance arteries from patients with cardiovascular disease

    DEFF Research Database (Denmark)

    Leurgans, Thomas M; Bloksgaard, Maria; Brewer, Jonathan R

    2016-01-01

    -activated K(+) -channels, but markedly blunted by catalase during ET-1-induced contraction. This catalase-sensitive relaxation was not modified by inhibitors of NADPH oxidases or allopurinol. Exogenous H2 O2 caused significantly larger relaxation of ET-1- than K(+) - or U46619-induced contraction...... arteries exposed to ET-1, involvement of nitric oxide (NO) in responses to an endothelium-dependent vasodilator is replaced by H2 O2 without notable contribution of NADPH oxidases, xanthine oxidase or NO synthases. This might have consequences for endothelial dysfunction in conditions where intra...

  13. ANTIPLATELET DRUGS RESISTANCE IN PATIENTS WITH ISCHEMIC HEART DISEASE AND OBLITERATIVE ATHEROSCLEROSIS OF LOWER LIMB ARTERIES ASSOCIATED WITH DIABETES MELLITUS TYPE 2

    Directory of Open Access Journals (Sweden)

    E. V. Gorjacheva

    2016-01-01

    Full Text Available Aim. To study a rate of resistance to acetylsalicylic acid (ASA and clopidogrel and clinical outcomes in patients with atherosclerosis and diabetes mellitus type 2 (DM2.Material and methods. 154 patients were involved in the study and split into two groups. 100 patients (47 men, 53 women; aged 66,4±7,8 y.o. with ischemic heart disease (IHD (which was presented by angina pectoris, class I-III, or myocardial infarction history were included into the first group (G1. Other 54 patients (38 men, 16 women; aged 64,1±10,2 y.o. with IHD associated with obliterative atherosclerosis of lower limb were included into the 2nd group (G2. Platelet aggregation was evaluated by Born's method (inducers of platelet aggregation were arachidonic acid and ADP. Reduction of platelet aggregation ≥20% after arachidonic acid induction was considered as criterion of resistance to ASA. Patients were considered as resistant, partly resistant and sensitive to clopidogrel if platelet aggregation reduced on <10%, 10-29%, and ≥30% respectively.Results. Rate of ASA and clopidogrel resistance in patients with DM2 was significantly higher than these in patients without DM2 (48% vs 16% respectively, р=0,003 in G1; 42% vs 7% respectively, р=0,007 in G2.Conclusion. Resistance to antiplatelet drugs is observed more often in patients with DM2 and can result in increased risk of cardiovascular complications.

  14. ANTIPLATELET DRUGS RESISTANCE IN PATIENTS WITH ISCHEMIC HEART DISEASE AND OBLITERATIVE ATHEROSCLEROSIS OF LOWER LIMB ARTERIES ASSOCIATED WITH DIABETES MELLITUS TYPE 2

    Directory of Open Access Journals (Sweden)

    E. V. Gorjacheva

    2009-01-01

    Full Text Available Aim. To study a rate of resistance to acetylsalicylic acid (ASA and clopidogrel and clinical outcomes in patients with atherosclerosis and diabetes mellitus type 2 (DM2.Material and methods. 154 patients were involved in the study and split into two groups. 100 patients (47 men, 53 women; aged 66,4±7,8 y.o. with ischemic heart disease (IHD (which was presented by angina pectoris, class I-III, or myocardial infarction history were included into the first group (G1. Other 54 patients (38 men, 16 women; aged 64,1±10,2 y.o. with IHD associated with obliterative atherosclerosis of lower limb were included into the 2nd group (G2. Platelet aggregation was evaluated by Born's method (inducers of platelet aggregation were arachidonic acid and ADP. Reduction of platelet aggregation ≥20% after arachidonic acid induction was considered as criterion of resistance to ASA. Patients were considered as resistant, partly resistant and sensitive to clopidogrel if platelet aggregation reduced on <10%, 10-29%, and ≥30% respectively.Results. Rate of ASA and clopidogrel resistance in patients with DM2 was significantly higher than these in patients without DM2 (48% vs 16% respectively, р=0,003 in G1; 42% vs 7% respectively, р=0,007 in G2.Conclusion. Resistance to antiplatelet drugs is observed more often in patients with DM2 and can result in increased risk of cardiovascular complications.

  15. Accuracy of arterial spin labeling magnetic resonance imaging (MRI) perfusion in detecting the epileptogenic zone in patients with drug-resistant neocortical epilepsy: comparison with electrophysiological data, structural MRI, SISCOM and FDG-PET.

    Science.gov (United States)

    Sierra-Marcos, A; Carreño, M; Setoain, X; López-Rueda, A; Aparicio, J; Donaire, A; Bargalló, N

    2016-01-01

    Locating the epileptogenic zone (EZ) in patients with neocortical epilepsy presents major challenges. Our aim was to assess the accuracy of arterial spin labeling (ASL), an emerging non-invasive magnetic resonance imaging (MRI) perfusion technique, to locate the EZ in patients with drug-resistant neocortical epilepsy. Twenty-five consecutive patients with neocortical epilepsy referred to our epilepsy unit for pre-surgical evaluation underwent a standardized assessment including video-electroencephalography (EEG) monitoring, structural MRI, subtraction ictal single-photon emission computed tomography co-registered to MRI (SISCOM) and fluorodeoxyglucose positron emission tomography (FDG-PET) studies. An ASL sequence was included in the MRI studies. Areas of hypoperfusion or hyperperfusion on ASL were classified into 15 anatomic-functional cortical regions; these regional cerebral blood flow maps were compared with the EZ determined by the other tests and the strength of concordance was assessed with the kappa coefficient. Of the 25 patients [16 (64%) women; mean age 32.4 (±13.8) years], 18 (72%) had lesions on structural MRI. ASL abnormalities were seen in 15 (60%) patients (nine hypoperfusion, six hyperperfusion). ASL had a very good concordance with FDG-PET (k = 0.84), a good concordance with structural MRI (k = 0.76), a moderate concordance with video-EEG monitoring (k = 0.53) and a fair concordance with SISCOM (k = 0.28). Arterial spin labeling might help to confirm the location and extent of the EZ in the pre-surgical workup of patients with drug-resistant neocortical epilepsy. © 2015 EAN.

  16. Atherosclerotic Renal Artery Stenosis.

    Science.gov (United States)

    Schoepe, Robert; McQuillan, Stephen; Valsan, Debbie; Teehan, Geoffrey

    2017-01-01

    Atherosclerotic Renal Artery Stenosis is a form or peripheral arterial disease that tends to affect older subjects with hyperlipidemia, history of tobacco use, and who have other coexistent forms of vascular insufficiency. An abdominal bruit on physical exam can be a helpful clue. Slowly progressive, it can lead to critical narrowing of the renal arteries which creates a cascade of events such as renin-angiotensin-aldosterone activation (RAAS), hypertension, acute pulmonary edema, and renal fibrosis. The hypertension is considered a secondary form and can even be resistant to multiple antihypertensives. The diagnosis can be made with imaging (duplex ultrasound CT scans, MRA, or angiography). Because of the unique circulation to the kidney, stenting and angioplasty are rarely curative. This was confirmed in three recent large clinical trials. Therapy consists of lipid and blood pressure control, and dual anti-platelet agents. Because the disease activates the RAAS system, ace inhibitors and angiotensin receptor blockers can be useful agents but carry the risk of ischemic nephropathy, a form of acute kidney injury related to reduced renal blood flow after challenge with these agents. As such these agents are used with caution. Little is known about optimal blood pressure agents or the effect of lifestyle modification.

  17. Muscle fatigue in frog semitendinosus: alterations in contractile function

    Science.gov (United States)

    Thompson, L. V.; Balog, E. M.; Riley, D. A.; Fitts, R. H.

    1992-01-01

    The purpose of this study was to characterize the contractile properties of the frog semitendinosus (ST) muscle before and during recovery from fatigue, to relate the observed functional changes to alterations in specific steps in the crossbridge model of muscle contraction, and to determine how fatigue affects the force-frequency relationship. The frog ST (22 degrees C) was fatigued by direct electrical stimulation with 100-ms 150-Hz trains at 1/s for 5 min. The fatigue protocol reduced peak twitch (Pt) and tetanic (Po) force to 32 and 8.5% of initial force, respectively. The decline in Pt was less than Po, in part due to a prolongation in the isometric contraction time (CT), which increased to 300% of the initial value. The isometric twitch duration was greatly prolonged as reflected by the lengthened CT and the 800% increase in the one-half relaxation time (1/2RT). Both Pt and Po showed a biphasic recovery, a rapid initial phase (2 min) followed by a slower (40 min) return to the prefatigue force. CT and 1/2RT also recovered in two phases, returning to 160 and 265% of control in the first 5 min. CT returned to the prefatigue value between 35 and 40 min, whereas even at 60 min 1/2RT was 133% of control. The maximal velocity of shortening, determined by the slack test, was significantly reduced [from 6.7 +/- 0.5 to 2.5 +/- 0.4 optimal muscle length/s] at fatigue. The force-frequency relationship was shifted to the left, so that optimal frequency for generating Po was reduced.(ABSTRACT TRUNCATED AT 250 WORDS).

  18. LPS and cytokines inhibit rat cardiomyocyte contractility in vitro

    Science.gov (United States)

    Hobai, Ion A.; Morse, Justin C.; Siwik, Deborah A.; Colucci, Wilson S.

    2014-01-01

    Background Sepsis-induced cardiomyopathy (SIC) is thought to be the result of detrimental effects of inflammatory mediators on cardiac muscle. Here we studied the effects of prolonged (24 ± 4 h) exposure of adult rat ventricular myocytes (ARVM) to bacterial lipopolysaccharide (LPS) and inflammatory cytokines tumor necrosis factor (TNF) and interleukins-1 (IL-1) and -6 (IL-6). Materials and methods We measured sarcomere shortening (SS) and cellular calcium (Ca2+) transients (ΔCai, with fura-2AM) in isolated cardiomyocytes externally paced at 5Hz at 37 °C. Results SS decreased after incubation with LPS (100 µg/ml), IL-1 (100 ng/ml) and IL-6 (30 ng/ml), but not with lesser doses of these mediators, or TNF (10 –100 ng/ml). A combination of LPS (100 µg/ml), TNF, IL-1 and IL-6 (each 100 ng/ml; i.e. “Cytomix-100”) induced a maximal decrease in SS and ΔCai. Sarcoplasmic reticulum (SR) Ca2+ load (CaSR, measured with caffeine) was unchanged by Cytomix-100, however, SR fractional release (ΔCai/CaSR) was decreased. Underlying these effects, Ca2+ influx into the cell (via L-type Ca2+ channels) and Ca2+ extrusion via Na+/Ca2+ exchange were decreased by Cytomix-100. SR Ca2+ pump (SERCA) was not affected. Conclusions Prolonged exposure of ARVM to a mixture of LPS and inflammatory cytokines inhibits cell contractility. The effect is mediated by the inhibition of Ca2+ influx via LTCC, and partially opposed by the inhibition of Na+/Ca2+ exchange. Since both mechanisms are commonly seen in animal models of SIC, we conclude that prolonged challenge with Cytomix-100 of ARVM may represent an accurate in vitro model for SIC. PMID:25439505

  19. Lipopolysaccharide and cytokines inhibit rat cardiomyocyte contractility in vitro.

    Science.gov (United States)

    Hobai, Ion A; Morse, Justin C; Siwik, Deborah A; Colucci, Wilson S

    2015-02-01

    Sepsis-induced cardiomyopathy (SIC) is thought to be the result of detrimental effects of inflammatory mediators on the cardiac muscle. Here we studied the effects of prolonged (24 ± 4 h) exposure of adult rat ventricular myocytes (ARVM) to bacterial lipopolysaccharide (LPS) and inflammatory cytokines tumor necrosis factor (TNF) and interleukins-1 (IL-1) and IL-6. We measured sarcomere shortening (SS) and cellular calcium (Ca(2+)) transients (ΔCai, with fura-2 AM) in isolated cardiomyocytes externally paced at 5 Hz at 37°C. SS decreased after incubation with LPS (100 μg/mL), IL-1 (100 ng/mL), and IL-6 (30 ng/mL), but not with lesser doses of these mediators, or TNF (10-100 ng/mL). A combination of LPS (100 μg/mL), TNF, IL-1, and IL-6 (each 100 ng/mL; i.e., "Cytomix-100") induced a maximal decrease in SS and ΔCai. Sarcoplasmic reticulum (SR) Ca(2+) load (CaSR, measured with caffeine) was unchanged by Cytomix-100; however, SR fractional release (ΔCai/CaSR) was decreased. Underlying these effects, Ca(2+) influx into the cell (via L-type Ca(2+) channels, LTCC) and Ca(2+) extrusion via Na(+)/Ca(2+) exchange were decreased by Cytomix-100. SR Ca(2+) pump (SERCA) (SR Ca(2+) ATPase) was not affected. Prolonged exposure of ARVM to a mixture of LPS and inflammatory cytokines inhibits cell contractility. The effect is mediated by the inhibition of Ca(2+) influx via LTCC, and partially opposed by the inhibition of Na(+)/Ca(2+) exchange. Because both mechanisms are commonly seen in animal models of SIC, we conclude that prolonged challenge with Cytomix-100 of ARVM may represent an accurate in vitro model for SIC. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Características fenotípicas da hipertensão arterial resistente na população brasileira Phenotypic characteristics of resistant hypertension in the Brazilian population

    Directory of Open Access Journals (Sweden)

    Ana Paula Cabral de Faria

    2013-01-01

    Full Text Available Hipertensão resistente (HAR é definida como a pressão arterial que permanece acima da meta pressórica, apesar do uso de três classes de anti-hipertensivos em doses otimizadas, sendo um deles um diurético. Além disso, são considerados também hipertensos resistentes os pacientes que usam quatro ou mais classes e possuem suas pressões controladas. Embora essa definição seja útil na categorização de um maior grupo de resistentes, visto esses dois subgrupos compartilharem alto risco cardiovascular, algumas importantes particularidades clínicas e fisiopatológicas necessitam ser mais bem avaliadas antes de resistentes controlados e não controlados pertencerem ao mesmo grupo. Foram comparadas algumas características cardiovasculares nesses dois subgrupos de hipertensos resistentes. Embora algumas semelhanças, o subgrupo HRNC apresenta fenótipos cardiovasculares com pior prognóstico como maior rigidez vascular e hipertrofia ventricular esquerda, além de função endotelial mais prejudicada e menor queda de pressão arterial no período noturno, entre outras. Frente às diferenças, o subgrupo HRNC está associado à maior risco cardiovascular, podendo ser considerado mais resistente ao tratamento anti-hipertensivo. Além da importância de melhor prevenção e tratamento da HAR com medidas de identificar precocemente os fatores de risco e otimizar a terapia farmacológica, algumas implicações clínicas devem ser consideradas na abordagem de pacientes controlados e não controlados como semelhantes ao grupo de resistentes.Resistant hypertension (RH is defined as blood pressure that remains above target in spite of the concurrent use of three or more classes of antihypertensive drugs at optimized doses (UCRH, with one of them being a diuretic. Moreover, patients whose blood pressure is controlled while using four or more antihypertensive medications are also considered controlled resistant hypertensive (CRH subjects. Although this

  1. Double profunda brachii artery

    Directory of Open Access Journals (Sweden)

    Gavishiddappa A Hadimani

    2016-01-01

    Full Text Available Brachial artery (BA is a continuation of the axillary artery at the lower border of teres major. In the cubital fossa, BA divides into radial artery and ulnar artery as terminal branches. Large branch given from the BA in the upper part is profunda brachii artery. In the present case, we noticed double profunda brachii that arises from the BA. They are profunda brachii artery 1 and profunda brachii artery 2. Profunda brachii artery 1 arises in the proximal part of the BA and profunda brachii artery 2 arises distal to the profunda brachii artery 1. Both the arteries run inferolaterally in the spiral groove along with radial nerve. Variations of profunda brachii artery are important during harvesting of the lateral arm flaps and may lead to inadvertent injury during percutaneous arterial catheterization or injection of drugs.

  2. In vivo experimental stroke and in vitro organ culture induce similar changes in vasoconstrictor receptors and intracellular calcium handling in rat cerebral arteries

    DEFF Research Database (Denmark)

    Povlsen, Gro Klitgaard; Waldsee, Roya; Ahnstedt, Hilda

    2012-01-01

    Cerebral arteries subjected to different types of experimental stroke upregulate their expression of certain G-protein-coupled vasoconstrictor receptors, a phenomenon that worsens the ischemic brain damage. Upregulation of contractile endothelin B (ET(B)) and 5-hydroxytryptamine 1B (5-HT(1B)) rec...

  3. Comparative effects of N-acetyl-L-cysteine and ramipril on arterial hypertension, insulin resistance, and oxidative stress in chronically glucose-fed rats.

    Science.gov (United States)

    El Midaoui, Adil; Ismael, Mahmoud Ali; Lu, Huogen; Fantus, I George; de Champlain, Jacques; Couture, Réjean

    2008-11-01

    Beneficial effects of an antioxidant (N-acetyl-L-cysteine, NAC) and an angiotensin I-converting enzyme (ACE) inhibitor (ramipril) were assessed in a rat model of insulin resistance induced by 10% glucose feeding for 20 weeks. Treatments with NAC (2 g/kg per day) and ramipril (1 mg/kg per day) were initiated at 16 weeks in the drinking fluid. Systolic blood pressure, plasma levels of insulin and glucose, and insulin resistance were significantly higher in rats treated with glucose for 20 weeks. This was associated with a higher production of superoxide anion and NADPH oxidase activity in aorta and liver and with a marked reduction in protein expression of skeletal muscle insulin receptor substrate-1 (IRS-1) in the gastrocnemius muscle. NAC prevented all these alterations. Although ramipril also reversed high blood pressure, it had a lesser effect on insulin resistance (including IRS-1) and blocked superoxide anion production only in aorta. Ramipril, in contrast to NAC, did not reduce NADPH oxidase activity in aorta and liver or plasma levels of 4-hydroxynonenal and malondialdehyde. Results suggest that the inhibition of the oxidative stress in hypertensive and insulin-resistant states contributes to the therapeutic effects of NAC and ramipril. Whereas NAC exerts effective antioxidant activity in multiple tissues, ramipril appears to preferentially target the vasculature.

  4. The influence of steroids on noradrenaline-mediated contractile reactivity of the superficial nasal and facial veins in cycling gilts.

    Science.gov (United States)

    Grzegorzewski, W J; Muszak, J; Wasowska, B; Jan, B; Stefańczyk-Krzymowska, S

    2012-01-01

    The nasal venous blood may be directed through the facial vein into the systemic circulation or through the frontal vein into the venous cavernous sinus of the perihypophyseal vascular complex, where hormones and pheromones permeate from the venous blood into the arterial blood supplying the brain and hypophysis. The present study was designed to determine the effect of noradrenaline (NA) on the tension of the nasal, frontal and facial veins of cycling gilts, and influence of ovarian steroid hormones on NA-mediated contractile reactivity. Additionally, the enzyme dopamine-beta-hydroxylase catalysing the conversion of dopamine to noradrenaline (DbetaH) was immunolocalized in these vessels. Among three studied veins, the frontal proximal vein, that fulfill a key role in the supply of the nasal venous blood into the venous cavernous sinus, reacted to NA most strongly (P tension of the frontal proximal vein during the periestrous period (P superficial nasal and facial veins of gilts in both studied stages of the estrous cycle. We suggest that the reactivity of the superficial veins of the nose and face to NA combined with the previously demonstrated reactivity of these veins to steroid ovarian hormones and male steroid pheromones may regulate the access of priming pheromone androstenol (resorebed in the nasal cavity) to the brain of gilts during periestrous period via humoral local destination transfer.

  5. Characterisation of the contractile dynamics of the resting ex vivo urinary bladder of the pig.

    Science.gov (United States)

    Lentle, Roger G; Reynolds, Gordon W; Janssen, Patrick W M; Hulls, Corrin M; King, Quinten M; Chambers, John Paul

    2015-12-01

    To characterise the area and movements of ongoing spontaneous localised contractions in the resting porcine urinary bladder and relate these to ambient intravesical pressure (Pves ), to further our understanding of their genesis and role in accommodating incoming urine. We used image analysis to quantify the areas and movements of discrete propagating patches of contraction (PPCs) on the anterior, anterolateral and posterior surfaces of the urinary bladders of six pigs maintained ex vivo with small incremental increases in volume. We then correlated the magnitude of Pves and cyclic changes in Pves with parameters derived from spatiotemporal maps. Contractile movements in the resting bladder consisted only of PPCs that covered around a fifth of the surface of the bladder, commenced at various sites, and were of ≈6 s in duration. They propagated at around 6 mm/s, mainly across the anterior and lateral surface of the bladder by various, sometimes circular, routes in a quasi-stable rhythm, and did not traverse the trigone. The frequencies of these rhythms were low (3.15 cycles/min) and broadly similar to those of cyclic changes in Pves (3.55 cycles/min). Each PPC was associated with a region of stretching (positive strain rate) and these events occurred in a background of more constant strain. The amplitudes of cycles in Pves and the areas undergoing PPCs increased after a sudden increase in Pves but the frequency of cycles of Pves and of origin of PPCs did not change. Peaks in Pves cycles occurred when PPCs were traversing the upper half of the bladder, which was more compliant. The velocity of propagation of PPCs was similar to that of transverse propagation of action potentials in bladder myocytes and significantly greater than that reported in interstitial cells. The size of PPCs, their frequency and their rate of propagation were not affected by intra-arterial dosage with tetrodotoxin or lidocaine. The origin and duration of PPCs influence both Pves and cyclic

  6. Pharmacological radionuclide ventriculography for detection of myocardial contractile reserve in patients after myocardial infarction: head-to-head comparison of low dose dobutamine and low dose dypiridamole

    International Nuclear Information System (INIS)

    Petrasinovic, Z.; Ostojic, M.; Beleslin, B.; Stojkovic, S.; Nedeljkovic, M.; Stankovic, G.; Dikic, A.; Pavlovic, S.; Sobic, D.

    2002-01-01

    Background. Low dose pharmacological stress echocardiography with either dobutamine or dipyridamole infusion has been proposed for recognition of myocardial viability. However, dependence on adequate acoustic window, observer experience, and the mild degree of wall motion changes make the viability assessment by stress echocardiography especially bothersome. The objective of the study was to evaluate the ability of low dose dobutamine and low dose dipyridamole radionuclide ventriculography to detect contractile reserve in patients after myocardial infarction and functional recovery after coronary angioplasty. Methods. The study group consisted of 20 consecutive patients (52±10 years, 17 male) with previous myocardial infarction and resting regional dyssynergy, in whom diagnostic cardiac catheterization revealed significant one-vessel coronary artery stenosis suitable for angioplasty. Each patient underwent equilibrium 99m-Tc radionuclide ventriculography which was performed at rest and during low dose dipyridamole (0.28 mg/kg over 2 minutes) and low dose dobutamine infusion (up to 10 mcg/kg/min). Left ventricular global and regional ejection fractions were determined. Increase of regional ejection fraction for >5% (inferoapical and posterolateral regions) or >10% (anteroseptal regions) during low dose dobutamine and dipyridamole in infarcted regions, as well as in the follow up period, was considered as index of contractile reserve. After 8 weeks of successful angioplasty, resting radionuclide ventriculography was repeated in all patients in order to identify functional recovery of the infarct zone. Results. Out of the 180 analyzed segments (20x9), 90 regional ejection fractions have shown depressed contractility. The mean of the regional ejection fractions showing depressed contractility increased from the resting value of 34±12% to 42±14% in the follow-up period (p=0.06). Of the 90 with baseline dyssynergy, 46 were responders during low-dose dobutamine (51

  7. The role of voltage-gated potassium channels in the regulation of mouse uterine contractility

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    Abel Peter W

    2007-11-01

    Full Text Available Abstract Background Uterine smooth muscle cells exhibit ionic currents that appear to be important in the control of uterine contractility, but how these currents might produce the changes in contractile activity seen in pregnant myometrium has not been established. There are conflicting reports concerning the role of voltage-gated potassium (Kv channels and large-conductance, calcium-activated potassium (BK channels in the regulation of uterine contractility. In this study we provide molecular and functional evidence for a role for Kv channels in the regulation of spontaneous contractile activity in mouse myometrium, and also demonstrate a change in Kv channel regulation of contractility in pregnant mouse myometrium. Methods Functional assays which evaluated the effects of channel blockers and various contractile agonists were accomplished by quantifying contractility of isolated uterine smooth muscle obtained from nonpregnant mice as well as mice at various stages of pregnancy. Expression of Kv channel proteins in isolated uterine smooth muscle was evaluated by Western blots. Results The Kv channel blocker 4-aminopyridine (4-AP caused contractions in nonpregnant mouse myometrium (EC50 = 54 micromolar, maximal effect at 300 micromolar but this effect disappeared in pregnant mice; similarly, the Kv4.2/Kv4.3 blocker phrixotoxin-2 caused contractions in nonpregnant, but not pregnant, myometrium. Contractile responses to 4-AP were not dependent upon nerves, as neither tetrodotoxin nor storage of tissues at room temperature significantly altered these responses, nor were responses dependent upon the presence of the endometrium. Spontaneous contractions and contractions in response to 4-AP did not appear to be mediated by BK, as the BK channel-selective blockers iberiotoxin, verruculogen, or tetraethylammonium failed to affect either spontaneous contractions or 4-AP-elicited responses. A number of different Kv channel alpha subunit proteins were

  8. 17 alpha-hydroxyprogesterone caproate vehicle, castor oil, enhances the contractile effect of oxytocin in human myometrium in pregnancy.

    Science.gov (United States)

    O'Sullivan, Michael D; Hehir, Mark P; O'Brien, Yvonne M; Morrison, John J

    2010-05-01

    The possibility exists that the vehicle for 17-alpha-hydroxyprogesterone caproate, castor oil, exerts an effect on human uterine contractility. The aim of this study was to evaluate its effects on contractility of myometrial preparations that were obtained during pregnancy. Myometrial strips were suspended under isometric conditions. Contractility was induced with oxytocin. Strips were incubated in castor oil or physiologic salt solution and suspended for a further oxytocin challenge. Contractile integrals were compared between both groups. Strips that were exposed to castor oil demonstrated increased contractile activity that was elicited by oxytocin (mean contractility value, 165.53%+/-17.03%; n=8; P=.004), compared with control strips (mean contractility value, 72.57%+/-7.48%; n=8; P=.003). There was a significant increase in contractile activity of the castor oil-exposed strips, compared with those that were exposed to physiologic salt solution (n=8; Pcastor oil results in enhanced oxytocin-induced contractility. Copyright (c) 2010 Mosby, Inc. All rights reserved.

  9. Magnitude-dependent proliferation and contractility modulation of human bladder smooth muscle cells under physiological stretch.

    Science.gov (United States)

    Luo, De-Yi; Wazir, Romel; Du, Caigan; Tian, Ye; Yue, Xuan; Wei, Tang-Qiang; Wang, Kun-Jie

    2015-11-01

    The purpose of this study was to describe and test a kind of stretch pattern which is based on modified BOSE BioDynamic system to produce optimum physiological stretch during bladder cycle. Moreover, we aimed to emphasize the effects of physiological stretch's amplitude upon proliferation and contractility of human bladder smooth muscle cells (HBSMCs). HBSMCs were seeded onto silicone membrane and subjected to stretch simulating bladder cycle at the range of stretches and time according to customized software on modified BOSE BioDynamic bioreactor. Morphological changes were assessed using immunofluorescence and confocal laser scanning microscope. Cell proliferation and cell viability were determined by BrdU incorporation assay and Cell Counting Kit-8, respectively. Contractility of the cells was determined using collagen gel contraction assay. RT-PCR was used to assess phenotypic and contractility markers. HBSMCs were found to show morphologically spindle-shaped and orientation at various elongations in the modified bioreactor. Stretch-induced proliferation and viability depended on the magnitude of stretch, and stretches also regulate contractility and contraction markers in a magnitude-dependent manner. We described and tested a kind of stretch pattern which delivers physiological stretch implemented during bladder cycle. The findings also showed that mechanical stretch can promote magnitude-dependent morphological, proliferative and contractile modulation of HBSMCs in vitro.

  10. Inhibition of isolated human myometrium contractility by minoxidil and reversal by glibenclamide.

    Science.gov (United States)

    Prabhakaran, S S; Dhanasekar, K R; Thomas, E; Jose, R; Peedicayil, J; Samuel, P

    2010-03-01

    This study investigated the ability of the antihypertensive drug minoxidil to inhibit potassium chloride (KCl)-induced contractility of the isolated human myometrium. Twelve strips of myometrium obtained from 12 patients who underwent hysterectomy were triggered to contract with 55 mM KCl before and after incubation with 3 concentrations (1, 3 and 10 microM) of minoxidil. The percent inhibition by minoxidil on the extent of contraction, and the area under the contractile curve of KCl-induced contraction of the myometrial strips was determined. Furthermore, the effect of 10 microM glibenclamide on the inhibition generated by 3 microM minoxidil on KCl-induced contractility was studied. It was found that minoxidil produced a concentration-dependent inhibition of KCl-induced contractility of the myometrium and that glibenclamide reversed this inhibitory effect. These results suggest that the inhibitory effect of minoxidil on isolated human myometrium contractility may prove useful in clinical conditions requiring relaxation of the myometrium. 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

  11. Quantitative determination of arterial wall mechanics with pulse oximetric finger plethysmography.

    Science.gov (United States)

    Kato, R; Sato, J; Iuchi, T; Higuchi, Y

    1999-10-30

    The plethysmographic wave of pulse oximetry reflects arterial pulsation at the fingertip. Since arterial pressure and the pulsatile component of the arterial cross section represent the input and output of the fingertip arterial system, respectively, arterial wall mechanics may be delineated from their relationship. We aimed to construct a mathematical model of the fingertip arterial wall from the relationship between the plethysmographic wave and arterial pressure. The pulse oximetric plethysmographic signal at the forefinger and pressure at the ipsilateral radial artery were measured. Employing the data, simple mathematical models with one to four mechanical elements were tested in terms of the goodness of fit and the physiological implications. The determined model was applied to the data obtained during administration of vasoactive agents in anesthetized patients. The mathematical model suited for describing arterial wall mechanics was a four-element, two-compartment model. The two compartments represent passive mechanical and active contractile properties, respectively. In the application of the model to the anesthetized patients, the vasoactive agents produced changes in the model parameters that implied mechanical alterations in the arterial wall. These findings suggest the benefit of the four-element, two-compartment model in analyzing peripheral vascular wall mechanics influenced by various stimuli in intensive care and anesthesia.

  12. Coronary artery disease (image)

    Science.gov (United States)

    ... through these arteries is critical for the heart. Coronary artery disease usually results from the build-up of fatty material and plaque, a condition called atherosclerosis. As the coronary arteries narrow, the flow of blood to the ...

  13. Carotid Artery Disease

    Science.gov (United States)

    ... head with blood. If you have carotid artery disease, the arteries become narrow or blocked, usually because ... other substances found in the blood. Carotid artery disease is serious because it can block the blood ...

  14. Arterial function of carotid and brachial arteries in postmenopausal vegetarians

    Directory of Open Access Journals (Sweden)

    Su T

    2011-08-01

    Full Text Available Ta-Chen Su1, Pao-Ling Torng2, Jiann-Shing Jeng3, Ming-Fong Chen1, Chiau-Suong Liau1,41Division of Cardiology, Department of Internal Medicine, 2Department of Obstetrics and Gynecology, 3Department of Neurology, National Taiwan University Hospital, National Taiwan University College of Medicine, 4Cardiovascular Center, Taipei Buddist Tzu-Chi Hospital, Hsin-Dian, Taipei, TaiwanBackground: Vegetarianism is associated with a lower risk of cardiovascular disease. However, studies of arterial function in vegetarians are limited.Methods: This study investigated arterial function in vegetarianism by comparing 49 healthy postmenopausal vegetarians with 41 age-matched omnivores. The arterial function of the common carotid artery was assessed by carotid duplex, while the pulse dynamics method was used to measure brachial artery distensibility (BAD, compliance (BAC, and resistance (BAR. Fasting blood levels of glucose, lipids, lipoprotein (a, high-sensitivity C-reactive protein, homocysteine, and vitamin B12 were also measured.Results: Vegetarians had significantly lower serum cholesterol, high-density and low-density lipoprotein, and glucose compared with omnivores. They also had lower vitamin B12 but higher homocysteine levels. Serum levels of lipoprotein (a and high-sensitivity C-reactive protein were no different between the two groups. There were no significant differences in carotid beta stiffness index, BAC, and BAD between the two groups even after adjustment for associated covariates. However, BAR was significantly lower in vegetarians than in omnivores. Multiple linear regression analysis revealed that age and pulse pressure were two important determinants of carotid beta stiffness index and BAD. Vegetarianism is not associated with better arterial elasticity.Conclusion: Apparently healthy postmenopausal vegetarians are not significantly better in terms of carotid beta stiffness index, BAC, and BAD, but have significantly decreased BAR than

  15. Mechanisms of vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34 in rat bone resistance arteries.

    Science.gov (United States)

    Benson, T; Menezes, T; Campbell, J; Bice, A; Hood, B; Prisby, R

    2016-05-01

    Parathyroid hormone (PTH) augments bone metabolism and bone mass when given intermittently. Enhanced blood flow is requisite to support high tissue metabolism. The bone arteries are responsive to all three PTH analogs, which may serve to augment skeletal blood flow during intermittent PTH administration. PTH augments bone metabolism. Yet, mechanisms by which PTH regulates bone blood vessels are unknown. We deciphered (1) endothelium-dependent and endothelium-independent vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34, (2) the signaling pathways (i.e., endothelial nitric oxide synthase [eNOS], cyclooxygenase [COX], protein kinase C [PKC], and protein kinase A [PKA]), and (3) receptor activation. Femoral principal nutrient arteries (PNAs) were given cumulative doses (10(-13)-10(-8) M) of PTH 1-84, PTH 1-34, and PTHrP 1-34 with and without signaling pathway blockade. Vasodilation was also determined following endothelial cell removal (i.e., denudation), PTH 1 receptor (PTH1R) inhibition and to sodium nitroprusside (SNP; a nitric oxide [NO] donor). Vasodilation was lowest to PTH 1-34, and maximal dilation was highest to PTHrP 1-34. Inhibition of eNOS reduced vasodilation to PTH 1-84 (-80 %), PTH 1-34 (-66 %), and PTHrP 1-34 (-48 %), evidencing the contribution of NO. Vasodilation following denudation was eliminated (PTH 1-84 and PTHrP 1-34) and impaired (PTH 1-34, 17 % of maximum), highlighting the importance of endothelial cells for PTH signaling. Denuded and intact PNAs responded similarly to SNP. Both PKA and PKC inhibition diminished vasodilation in all three analogs to varying degrees. PTH1R blockade reduced vasodilation to 1, 12, and 12 % to PTH 1-84, PTH 1-34, and PTHrP 1-34, respectively. Vasodilation of femoral PNAs to the PTH analogs occurred via activation of the endothelial cell PTH1R for NO-mediated events. PTH 1-84 and PTHrP 1-34 primarily stimulated PKA signaling, and PTH 1-34 equally stimulated PKA and PKC signaling.

  16. Relationship between carotid artery stenosis and ischemic ocular diseases

    Directory of Open Access Journals (Sweden)

    Qian Chen

    2015-01-01

    Full Text Available AIM: To investigate the relationship between carotid artery stenosis and ischemic ocular diseases.METHODS: The clinical data of 30 cases(37 eyesof patients with ischemic eye diseases were collected from November 2010 to May 2014, and they were accepted the fundus fluorescein angiography(FFA, transcranial Doppler(TCDultrasonic blood vessels of the eye, neck vascular color Doppler flow imaging(CDFI, the neck CT angiography(CTAand carotid artery digital subtraction angiography(DSAexamination, and then the ischemic eye disease patients with ocular symptoms were analyzed. The peak systolic velocity(PSVand resistance index(RIof ophthalmic artery and central retinal artery were compared. Correlation between the internal carotid artery intima-media thickness(IMTand ophthalmic artery, central retinal artery PSV and RI correlation risk; ipsilateral internal carotid artery plaque and ophthalmic artery PSV and RI; PSV and RI associated ipsilateral internal carotid artery plaque and central retinal artery were analyzed. RESULTS: Eye symptoms: a black dim, reduced vision, the eyes flash, and around the eye pain were 75.7%, 83.8%, 51.4% and 32.4%; The eye signs: the dilatation of retinal vein, retinal hemorrhage, arterial stenosis and cotton spot and the contralateral side were regarded as main signs. Ophthalmic artery PSV and RI value of the differences were statistically significant(PPP>0.05; The ipsilateral internal carotid artery plaque and ophthalmic artery PSV had no correlation with RI values(P>0.05; PSV and RI and the ipsilateral internal carotid artery plaque and central retinal artery had no correlation(P>0.05.CONCLUSION: The incidence of ischemic eye diseases and internal carotid artery stenosis is associated with very close, the clinical can regard the degree of internal carotid artery stenosis as an important basis for diagnosis and treatment of eye diseases.

  17. Peripheral artery disease - legs

    Science.gov (United States)

    Peripheral vascular disease; PVD; PAD; Arteriosclerosis obliterans; Blockage of leg arteries; Claudication; Intermittent claudication; Vaso-occlusive disease of the legs; Arterial insufficiency of ...

  18. Plasticity of TOM complex assembly in skeletal muscle mitochondria in response to chronic contractile activity.

    Science.gov (United States)

    Joseph, Anna-Maria; Hood, David A

    2012-03-01

    We investigated the assembly of the TOM complex within skeletal muscle under conditions of chronic contractile activity-induced mitochondrial biogenesis. Tom40 import into mitochondria was increased by chronic contractile activity, as was its time-dependent assembly into the TOM complex. These changes coincided with contractile activity-induced augmentations in the expression of key protein import machinery components Tim17, Tim23, and Tom22, as well as the cytosolic chaperone Hsp90. These data indicate the adaptability of the TOM protein import complex and suggest a regulatory role for the assembly of this complex in exercise-induced mitochondrial biogenesis. Copyright © 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved. All rights reserved.

  19. Contractile properties are disrupted in Becker muscular dystrophy, but not in limb girdle type 2I

    DEFF Research Database (Denmark)

    Løkken, Nicoline; Hedermann, Gitte; Thomsen, Carsten

    2016-01-01

    We investigated whether a linear relationship between muscle strength and cross-sectional area (CSA) is preserved in calf muscles of patients with Becker muscular dystrophy (BMD, n = 14) and limb-girdle type 2I muscular dystrophy (LGMD2I, n = 11), before and after correcting for muscle fat...... infiltration. The Dixon magnetic resonance imaging technique was used to quantify fat and calculate a fat-free contractile CSA. Strength was assessed by dynamometry. Muscle strength/CSA relationships were significantly lower in patients versus controls. The strength/contractile-CSA relationship was still...... severely lowered in BMD, but was almost normalized in LGMD2I. Our findings suggest close to intact contractile properties in LGMD2I, which are severely disrupted in BMD. Ann Neurol 2016;80:466-471....

  20. Expression of the Receptor for Advanced Glycation End Products in Epicardial Fat: Link with Tissue Thickness and Local Insulin Resistance in Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Elena Dozio

    2016-01-01

    Full Text Available Increased expression of receptor for advanced glycation end products (RAGE in adipose tissue has been associated with inflammation, adipocyte hypertrophy, and impaired insulin signal. Epicardial adipose tissue (EAT, a visceral fat surrounding the myocardium, is potentially involved in the onset/progression of coronary artery disease (CAD. To date, the role of RAGE in EAT has not been explored much. We examined whether the RAGE expression in EAT was associated with EAT adiposity and metabolic dysfunctions normally found in CAD patients. EAT samples were obtained from 33 patients undergoing open-heart surgery. EAT expression of RAGE, GLUT4, adiponenctin, GLO1, HMGB1, TLR-4, and MyD88 was analyzed by microarray. EAT thickness was quantified by echocardiography. Anthropometric measures and clinical parameters were taken. BMI, HOMA-IR, and LAP indices were calculated. With increasing RAGE expression in EAT we observed increases in EAT thickness, reduced expression of GLUT4, adiponectin, and GLO1, and elevations of HMGB1, TLR-4, and MyD88. There were significant correlations between RAGE and EAT thickness and between RAGE and the genes. LAP was higher in patients with increased RAGE expression. Our data suggest that in CAD patients RAGE may be involved in promoting EAT adiposity and metabolic dysfunction, such as impaired insulin signaling.

  1. MAPK signaling pathway regulates cerebrovascular receptor expression in human cerebral arteries

    DEFF Research Database (Denmark)

    Ansar, Saema; Eftekhari, Sajedeh; Waldsee, Roya

    2013-01-01

    if the upregulation of contractile cerebrovascular receptors after 48 h of organ culture of human cerebral arteries involves MAPK pathways and if it can be prevented by a MEK1/2 inhibitor. Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into ring...... segments and incubated for 48 h in the presence or absence of the specific MEK1/2 inhibitor U0126. The vessels were then examined by using in vitro pharmacological methods and protein immunohistochemistry....

  2. Arterial hypertension and chronic liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, S

    2005-01-01

    This review looks at the alterations in the systemic haemodynamics of patients with chronic liver disease (cirrhosis) in relation to essential hypertension and arterial hypertension of renal origin. Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic...... vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counterregulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin......, calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during...

  3. The Effects of Histamine H3 Receptors on Contractile Responses on Rat Gastric Fundus

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    Aşkın Hekimoğlu

    2006-01-01

    Full Text Available The aim of this study is to determine the effects of histamine receptors on the gastrointestinal system smooth muscle contractions and the role of histamine H3 receptors on these effects. İsolated rat gastric fundus preparations were hanged on isolated organ bath and histamine receptor agonist and anthagonists were added to the bath solution and the electrical field stimulation-induced contractile responses were evaluated. In our study groups after blocking one of the histamine receptors H1, H2,H3; contractile responses were observed. Then, other two receptors were blocked one by one or combination of them to observe the changes on the contractile responses given to the electrical stimulation .To blocke histamine receptors pyrilamine (10-6м as H1 receptor blocker, famotidine (10-6м as H2 receptor blocker and thioperamide (10-5м as H3 receptor blocker and various combination of them were used. All groups were treated with H3 receptor anthagonist thioperamide (10-5м and agonist (R-α-methylhistamine (RMHA on 10-8, 10-7, 10-6 ve 10-5 molar concentrations cumulatively to observe its mediator effects on contractile responses. We suggested that (R-α-methylhistamine mediates the inhibition on the contractile effects of rat gastric fundus. This conclusion was supported by these findings: a the selective agonists (RMHA caused a dumping of the contractile effect of acetylcholine; b the effect of (RMHA was prevented by the selective H3 receptor antagonist thioperamide.

  4. Accessory left atrial diverticulae: contractile properties depicted with 64-slice cine-cardiac CT.

    LENUS (Irish Health Repository)

    Killeen, Ronan P

    2012-02-01

    To assess the contractility of accessory left atrial appendages (LAAs) using multiphasic cardiac CT. We retrospectively analyzed the presence, location, size and contractile properties of accessory LAAs using multiphasic cardiac 64-slice CT in 102 consecutive patients (63 males, 39 females, mean age 57). Multiplanar reformats were used to create image planes in axial oblique, sagittal oblique and coronal oblique planes. For all appendages with an orifice diameter >or= 10 mm, axial and sagittal diameters and appendage volumes were recorded in atrial diastole and systole. Regression analysis was performed to assess which imaging appearances best predicted accessory appendage contractility. Twenty-three (23%) patients demonstrated an accessory LAA, all identified along the anterior LA wall. Dimensions for axial oblique (AOD) and sagittal oblique (SOD) diameters and sagittal oblique length (SOL) were 6.3-19, 3.4-20 and 5-21 mm, respectively. All appendages (>or=10 mm) demonstrated significant contraction during atrial systole (greatest diameter reduction was AOD [3.8 mm, 27%]). Significant correlations were noted between AOD-contraction and AOD (R = 0.57, P < 0.05) and SOD-contraction and AOD, SOD and SOL (R = 0.6, P < 0.05). Mean diverticulum volume in atrial diastole was 468.4 +\\/- 493 mm(3) and in systole was 171.2 +\\/- 122 mm(3), indicating a mean change in volume of 297.2 +\\/- 390 mm(3), P < 0.0001. Stepwise multiple regression analysis revealed SOL to be the strongest independent predictor of appendage contractility (R(2) = 0.86, P < 0.0001) followed by SOD (R(2) = 0.91, P < 0.0001). Accessory LAAs show significant contractile properties on cardiac CT. Those accessory LAAs with a large sagittal height or depth should be evaluated for contractile properties, and if present should be examined for ectopic activity during electrophysiological studies.

  5. Store-operated Ca2+ entry supports contractile function in hearts of hibernators.

    Directory of Open Access Journals (Sweden)

    Olga V Nakipova

    Full Text Available Hibernators have a distinctive ability to adapt to seasonal changes of body temperature in a range between 37°C and near freezing, exhibiting, among other features, a unique reversibility of cardiac contractility. The adaptation of myocardial contractility in hibernation state relies on alterations of excitation contraction coupling, which becomes less-dependent from extracellular Ca2+ entry and is predominantly controlled by Ca2+ release from sarcoplasmic reticulum, replenished by the Ca2+-ATPase (SERCA. We found that the specific SERCA inhibitor cyclopiazonic acid (CPA, in contrast to its effect in papillary muscles (PM from rat hearts, did not reduce but rather potentiated contractility of PM from hibernating ground squirrels (GS. In GS ventricles we identified drastically elevated, compared to rats, expression of Orai1, Stim1 and Trpc1/3/4/5/6/7 mRNAs, putative components of store operated Ca2+ channels (SOC. Trpc3 protein levels were found increased in winter compared to summer GS, yet levels of Trpc5, Trpc6 or Trpc7 remained unchanged. Under suppressed voltage-dependent K+, Na+ and Ca2+ currents, the SOC inhibitor 2-aminoethyl diphenylborinate (2-APB diminished whole-cell membrane currents in isolated cardiomyocytes from hibernating GS, but not from rats. During cooling-reheating cycles (30°C-7°C-30°C of ground squirrel PM, 2-APB did not affect typical CPA-sensitive elevation of contractile force at low temperatures, but precluded the contractility at 30°C before and after the cooling. Wash-out of 2-APB reversed PM contractility to control values. Thus, we suggest that SOC play a pivotal role in governing the ability of hibernator hearts to maintain their function during the transition in and out of hibernating states.

  6. Tropomyosin isoforms differentially affect muscle contractility in the head and body regions in the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Barnes, Dawn E; Watabe, Eichi; Ono, Kanako; Kwak, Euiyoung; Kuroyanagi, Hidehito; Ono, Shoichiro

    2018-03-01

    Tropomyosin, one of major actin-filament binding proteins, regulates actin-myosin interaction and actin filament stability. Multicellular organisms express a number of tropomyosin isoforms, but understanding of isoform-specific tropomyosin functions is incomplete. The nematode Caenorhabditis elegans has a single tropomyosin gene, lev-11 , which has been reported to express four isoforms by using two separate promoters and alternative splicing. Here, we report a fifth tropomyosin isoform, LEV-11O, which is produced by alternative splicing which includes a newly identified seventh exon, exon 7a. By visualizing specific splicing events in vivo , we find that exon 7a is predominantly selected in a subset of the body wall muscles in the head, while exon 7b, which is alternative to exon 7a, is utilized in the rest of the body. Point mutations in exon 7a and exon 7b cause resistance to levamisole-induced muscle contraction specifically in the head and the main body, respectively. Overexpression of LEV-11O, but not LEV-11A, in the main body results in weak levamisole resistance. These results demonstrate that specific tropomyosin isoforms are expressed in the head and body regions of the muscles and differentially contribute to the regulation of muscle contractility. © 2018 by The American Society for Cell Biology.

  7. Effects of transcutaneous electrical nerve stimulation (TENS) on arterial stiffness and blood pressure in resistant hypertensive individuals: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Vilela-Martin, José Fernando; Giollo-Junior, Luiz Tadeu; Chiappa, Gaspar Rogério; Cipriano-Junior, Gerson; Vieira, Paulo José Cardoso; dos Santos Ricardi, Fábio; Paz-Landim, Manoel Ildefonso; de Andrade, Days Oliveira; Cestário, Elizabeth do Espírito Santo; Cosenso-Martin, Luciana Neves; Yugar-Toledo, Juan Carlos; Cipullo, José Paulo

    2016-03-29

    Resistant hypertension (RH) treatment requires an adequate and intense therapeutic approach. However, the results are not always satisfactory despite intensive treatment. Of the different pathophysiological mechanisms involved in the pathogenesis of RH, sympathetic overstimulation and therapies that block the sympathetic system have been widely studied. These approaches, however, are invasive and expensive. Another possible approach is by transcutaneous electrical nerve stimulation (TENS), a noninvasive method that modulates activity by using low-frequency transcutaneous electrical stimulation to inhibit primary afferent pathways. Thus, the current study will evaluate the effect of applying TENS in the cervicothoracic region of subjects with RH and will seek to develop a new low-cost and readily available therapy to treat this group of hypertensive individuals. This is a randomized, single blind (subject), parallel-assignment study controlled with a sham group and including participants aged 40 to 70 years with resistant hypertension. The trial has two arms: the treatment and control (sham group). The treatment group will be submitted to the stimulation procedure (TENS). The sham group will not be submitted to stimulation. The primary outcomes will be a reduction in the peripheral blood pressure and adverse events. The secondary outcomes will be a reduction the central blood pressure. The study will last 30 days. The sample size was calculated assuming an alpha error of 5 % to reject the null hypothesis with a statistical power of 80 %, thereby resulting in 28 participants per group (intervention versus sham). In recent decades, RH has become very common and costly. Adequate control requires several drugs, and in many cases, treatment is not successful. Sympathetic nervous system inhibition by renal denervation and central inhibition have significant effects in reducing BP; however, these treatments are costly and invasive. Another type of sympathetic nervous

  8. Validation of an in vitro contractility assay using canine ventricular myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Harmer, A.R., E-mail: alex.harmer@astrazeneca.com; Abi-Gerges, N.; Morton, M.J.; Pullen, G.F.; Valentin, J.P.; Pollard, C.E.

    2012-04-15

    Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscope at ∼ 36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration–effect curves were constructed for each compound in 4–30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6–8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds. -- Highlights: ► Cardiac contractility is an important physiological function of the heart. ► Assessment of contractility is a logical part of pre-clinical drug safety testing. ► There are limited validated assays that predict effects of compounds on contractility. ► Using dog myocytes, we have developed an in vitro cardiac contractility assay. ► The assay predicted the in vivo contractility with a good level of accuracy.

  9. Spontaneous and α-adrenoceptor-induced contractility in human collecting lymphatic vessels require chloride

    DEFF Research Database (Denmark)

    Mohanakumar, Sheyanth; Majgaard, Jens; Telinius, Niklas

    2018-01-01

    - with the impermeant anion aspartate and inhibition of Cl- transport and channels with the clinical diuretics furosemide and bendroflumethiazide, as well as DIDS and NPPB. The molecular expression of calcium-activated chloride channels was investigated by RT-PCR and proteins localized using immunoreactivity....... Spontaneous and norepinephrine-induced contractility in human lymphatic vessels was highly abrogated after Cl- substitution with aspartate. 100‒300µM DIDS or NPPB inhibited spontaneous contractile behavior. Norepinephrine-stimulated tone was furthermore markedly abrogated by 200µM DIDS. Furosemide lowered...

  10. Effects of ageing on single muscle fibre contractile function following short-term immobilisation

    DEFF Research Database (Denmark)

    Hvid, Lars G; Ørtenblad, Niels; Aagaard, Per

    2011-01-01

    Very little attention has been given to the combined effect of healthy ageing and short-term disuse on the contractile function of human single muscle fibres. Therefore, the present study investigated the effects of 2 weeks of lower limb cast immobilisation (i.e. disuse) on selected contractile...... properties of single muscle fibres (n=378) from vastus lateralis of 9 young (24 ± 1 years) and 8 old (67 ± 2 years) healthy men with comparable levels of physical activity. Prior to immobilisation, MHC IIa fibres produced higher maximum Ca2+-activated force (approx. 32%) and specific force (approx. 33......%) and had lower Ca2+ sensitivity than MHC I fibres (p...

  11. Do knowledge of uterine artery resistance in the second trimester and targeted surveillance improve maternal and perinatal outcome? UTOPIA study: a randomized controlled trial.

    Science.gov (United States)

    García, B; Llurba, E; Valle, L; Gómez-Roig, M D; Juan, M; Pérez-Matos, C; Fernández, M; García-Hernández, J A; Alijotas-Reig, J; Higueras, M T; Calero, I; Goya, M; Pérez-Hoyos, S; Carreras, E; Cabero, L

    2016-06-01

    To ascertain whether screening for pre-eclampsia (PE) and intrauterine growth restriction (IUGR) by uterine artery (UtA) Doppler in the second trimester of pregnancy and targeted surveillance improve maternal and perinatal outcomes in an unselected population. This was a multicenter randomized open-label controlled trial. At the routine second-trimester anomaly scan, women were assigned randomly to UtA Doppler or non-Doppler groups. Women with abnormal UtA Doppler were offered intensive surveillance at high-risk clinics of the participating centers with visits every 4 weeks that included measurement of maternal blood pressure, dipstick proteinuria, fetal growth and Doppler examination. The primary outcome was a composite score for perinatal complications, defined as the presence of any of the following: PE, IUGR, spontaneous labor 90(th) percentile was able to detect 59% of early-onset PE and 60% of early-onset IUGR with a false-positive rate of 11.1%. When perinatal and maternal data according to assigned group (UtA Doppler vs non-Doppler) were compared, no differences were found in perinatal or maternal complications. However, screened patients had more medical interventions, such as corticosteroid administration (relative risk (RR), 1.79 (95% CI, 1.4-2.3)) and induction of labor for IUGR (RR, 1.36 (95% CI, 1.07-1.72)). In women developing PE or IUGR, there was a trend towards fewer maternal complications (RR, 0.46 (95% CI, 0.19-1.11)). Routine second-trimester UtA Doppler ultrasound in an unselected population identifies approximately 60% of women at risk for placental complications; however, application of this screening test failed to improve short-term maternal and neonatal morbidity and mortality. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

  12. Effects of 24-Week Aerobic and Resistance Training on Carotid Artery Intima-Media Thickness and Flow Velocity in Elderly Women with Sarcopenic Obesity.

    Science.gov (United States)

    Park, Jinkee; Kwon, Yoochan; Park, Hyuntea

    2017-11-01

    Sarcopenic obesity (SO) is closely associated with cardiovascular disease (CVD) in elderly women. Increases in body fat and decreases in muscle mass are closely associated with increased carotid intima-media thickness (CIMT). The aim of this study was to examine the influence of a 24-week aerobic and resistance training program on carotid parameters in SO. Fifty elderly women (74.1±6.1 years) with SO were randomly divided into an exercise group and a control group. The exercise group performed combined exercise over 24 weeks, consisting of resistance and aerobic training for 50-80 min, 5 times a week. Carotid variables were measured using B-mode ultrasound. The differences in the carotid variables and the relative changes between baseline and after 24 weeks were evaluated. In the analysis of variance (ANOVA) results, CIMT (p=0.013), systolic flow velocity (p=0.007), diastolic flow velocity (p=0.006), and wall shear rate (p=0.010) showed significant interactions. In paired t-test results of the exercise group, CIMT significantly decreased (p<0.01) and systolic flow velocity (p<0.01), diastolic flow velocity (p<0.001), and wall shear rate (p<0.05) significantly increased after 24 weeks. The 24-week combined exercise effectively decreased CIMT and increased carotid flow velocity and wall shear ratio. Therefore, combined exercise is thought to contribute to the improvement of the risk of CVD in elderly women with SO.

  13. Índices de resistência e pulsatilidade das artérias uterinas no primeiro e segundo trimestres de gestações normais Uterine arteries resistance and pulsatility indices at the first and second trimesters of normal pregnancies

    Directory of Open Access Journals (Sweden)

    Antonio Gadelha da Costa

    2010-06-01

    Full Text Available OBJETIVO: Determinar os índices de resistência (IR e pulsatilidade (IP nas artérias uterinas durante o primeiro e segundo trimestres de gestação. MATERIAIS E MÉTODOS: Realizamos estudo prospectivo longitudinal em 44 mulheres normais, da 8ª a 12ª e na 22ª semanas de gestação. A dopplervelocimetria foi realizada em ambas as artérias uterinas por meio do IR e do IP. Utilizamos volume de amostra de 1 a 2 mm, filtro de 50 a 70 Hz e ângulo de insonação abaixo de 60°. RESULTADOS: O IR e o IP da artéria uterina no primeiro trimestre foram maiores da 8ª a 12ª do que na 22ª semana de gestação. O IR e o IP da artéria uterina, no primeiro trimestre, com incisura foram de 0,83 ± 0,07 e 2,32 ± 0,79, e sem incisura, de 0,71 ± 0,16 e 1,61 ± 0,78, respectivamente. No segundo trimestre, o IR e o IP da artéria uterina com incisura foram de 0,59 ± 0,09 e 1,03 ± 0,32, e sem incisura, de 0,44 ± 0,09 e 0,63 ± 0,19, respectivamente. CONCLUSÃO: Estabelecemos os valores de referência do IR e do IP das artérias uterinas de gestantes normais no primeiro e segundo trimestres de gestação.OBJECTIVE: To determine uterine artery resistance index (RI and pulsatility index (PI during the first and second trimesters of pregnancy. MATERIALS AND METHODS: The authors developed a prospective longitudinal study with 44 healthy women at their 8th-12th and 22nd gestational weeks. Doppler velocimetry was utilized for evaluating RI and PI of both uterine arteries, with a sample volume of 1 to 2 mm, a 50-70 Hz filter, and an insonation angle < 60°. RESULTS: At 8th-12th gestational weeks, the uterine artery RI and PI were higher than at the 22nd gestational week. At the first trimester uterine artery RI and PI were, respectively, 0.83 ± 0.07 and 2.32 ± 0.79 with a notch, and 0.71 ± 0.16 and 1.61 ± 0.78, without a notch. At the second trimester, uterine artery RI and PI were, respectively, 0.59 ± 0.09 and 1.03 ± 0.32 with a notch, and 0.44 ± 0

  14. [Management of arterial hypertension].

    Science.gov (United States)

    Groha, P; Schunkert, H

    2015-09-01

    Arterial hypertension is one of the most frequent diseases in the western world and is one of the three most important risk factors for heart diseases. The 2013 guidelines of the European Societies of Hypertension and Cardiology (ESH/ESC) provide a clear action plan for evidence-based diagnostics and therapeutic measures in hypertensive subjects and simplify target blood pressures across various patient groups. Non-pharmacological options play a central role in the treatment of arterial hypertension. The indications for drug therapy arise from three criteria including the level of hypertension, risk profile of the patient, as well as response to non-pharmacological therapy. For the first choice monotherapy five substance groups are available: diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin (AT) 1 receptor antagonists and calcium antagonists. By combination therapy, the responder rate can be significantly increased with respect to a normalization of blood pressure. A true treatment resistance, in which the therapeutic goal is not reached in spite of a triple combination with maximum dosage, is extremely rare. Further treatment options are combinations of four drug classes and changes of medication. Hypertensive emergencies require a rapid intervention; nevertheless, the magnitude of blood pressure lowering can greatly vary depending on the individual clinical picture.

  15. Role of oxidative stress in angiotensin-II mediated contraction of human conduit arteries in patients with cardiovascular disease.

    Science.gov (United States)

    Püntmann, Valentina O; Hussain, Monira B; Mayr, Manuel; Xu, Qingbo; Singer, Donald R J

    2005-10-01

    Angiotensin II is a powerful vasoconstrictor involved in the development of high blood pressure and in the regulation of cardiovascular growth. Recent reports have suggested that in addition to the classical pathways involved in transducing responses to receptor activation, formation of reactive oxygen species by angiotensin II may also be involved. We investigated the importance of oxidative stress in angiotensin II induced contraction in human conduit arteries from patients with cardiovascular disease. Isometric contraction studies using human radial arteries entailed probes modulating the redox-dependent reactions to define the oxidative pathways involved in angiotensin II contraction. In situ oxidative fluorescence was employed to detect immediate superoxide tissue production in radial and internal mammary arteries. Treatment with TEMPOL, human superoxide dismutase, diphenyleneiodonium, oxypurinol, NG-monomethyl L-arginine considerably decreased contractile response to angiotensin II in radial arteries. Similarly, angiotensin II-stimulated arterial superoxide production was reduced in the presence of the above inhibitors. On the contrary, used as controls, norepinephrine vasoconstriction was not associated with increase of superoxide and neither ciprofloxacin nor aminophylline altered basal or angiotensin II induced superoxide generation. Our findings provide evidence for the role of oxidative pathways in contractile response of human conduit arteries to angiotensin II. Angiotensin II induced superoxide anion production may be mediated by multiple inter-dependent rate-limiting enzymes in both types of artery. Our studies may have important implication for future therapeutic approaches involving inhibition of angiotensin II mediated superoxide generation in hypertension and prevention of cardiovascular disease. We studied the role of oxidant species in contraction responses to angiotensin II in human conduit arteries. Treating radial artery segments with the

  16. Bestrophin is important for the rhythmic but not the tonic contraction in rat mesenteric small arteries

    DEFF Research Database (Denmark)

    Broegger, Torbjoern; Jacobsen, Jens Christian Brings; Secher Dam, Vibeke

    2011-01-01

    aimed to test this hypothesis by transfecting rat mesenteric small arteries in vivo with siRNA specifically targeting bestrophin-3. Methods and results The arteries were tested 3 days after transfection in vitro for isometric force development and for intracellular Ca2+ in SMCs. Bestrophin-3 expression...... was significantly reduced compared with arteries transfected with mutated siRNA. mRNA levels for bestrophin-1 and -2 were also significantly reduced by bestrophin-3 down-regulation. This is suggested to be secondary to specific bestrophin-3 down-regulation since siRNAs targeting different exons of the bestrophin-3...... gene had identical effects on bestrophin-1 and -2 expression. The transfection affected neither the maximal contractile response nor the sensitivity to norepinephrine and arginine-vasopressin. The amplitude of agonist-induced vasomotion was significantly reduced in arteries down...

  17. Bestrophin-3 associated Ca2+-activated Cl- conductance is important for synchronization in the arterial wall

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn; Aalkjær, Christian; Matchkov, Vladimir

    2009-01-01

    of bestrophin proteins family - Best-3. We have aimed here to explore the importance of Best-3 for vascular wall function.   Segments of the mesenteric small arteries were transfected in vivo in anaesthetized rats with siRNA against Best-3 and siRNA with mismatching nucleotides (mutated siRNA) as a control....... The efficiency of transfection at molecular level was evaluated 3 days after transfection. Contractility, vasomotion and [Ca2+]i dynamic were tested in isometric myograph and using confocal microscope.   The specific Best-3 siRNA significantly reduced Best-3 expression in comparison to the control. Arteries from......-cGMP to the endothelium-denuded vessels restored vasomotion but did not change the difference between groups. SMCs in control endothelium-intact arteries were completely synchronized whereas in the siRNA-transfected arteries only partial synchronization was observed.   Our data suggest that the Best-3-associated Ic...

  18. Regulatory mechanism of endothelin receptor B in the cerebral arteries after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Thigarajah, Rushani; Edvinsson, Lars

    2014-01-01

    drug targets to restore normal cerebral artery contractile function as part of successful neuroprotective therapy. METHODS: We have employed in vitro methods on human and rat cerebral arteries to study the regulatory mechanisms and the efficacy of target selective inhibitor, Mithramycin A (MitA...... arteries. RESULTS: Increased expression of specificity protein (Sp1) was observed in human and rat cerebral arteries after organ culture, strongly correlating with the ETBR upregulation. Similar observations were made in MCAO rats. Treatment with MitA, a Sp1 specific inhibitor, significantly downregulated...... vasoconstriction in focal cerebral ischemia via MEK-ERK signaling, which is also conserved in humans. The results show that MitA can effectively be used to block ETBR mediated vasoconstriction as a supplement to an existing ischemic stroke therapy....

  19. Long-term estradiol treatment improves VIP-mediated vasodilation in atherosclerotic proximal coronary arteries

    DEFF Research Database (Denmark)

    Dalsgaard, T.; Mortensen, Alicja; Larsen, C. R.

    2003-01-01

    arteries. Female ovariectomized homozygous Watanabe heritable hyperlipidemic rabbits were randomized to 16 weeks treatment with 17beta-estradiol or placebo. The diet was semisynthetic, thereby avoiding the influence of phytoestrogens. Artery ring segments were mounted for isometric tension recordings...... in myographs. Following precontraction, the dose-response relationships for VIP and PACAP were evaluated. Treatment with 17beta-estradiol significantly improved the maximum VIP-mediated vasodilation (E-max, percentage of precontraction) in proximal coronary arteries (45.8 +/- 9.6% vs. 24.1 +/- 3.7%, p ....05). In the same artery segment, 17β-estradiol induced a significant decrease in the relative ratio between the repeated contractile response to potassium 30 and 120 mM (100 +/- 7% vs. 132 +/- 11%, p

  20. New phenotypic aspects of the decidual spiral artery wall during early post-implantation mouse pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Elia, Artemis; Charalambous, Fotini [Department of Biological Sciences, University of Cyprus, University Campus, P.O. Box 20537, 1678 Nicosia (Cyprus); Georgiades, Pantelis, E-mail: pgeor@ucy.ac.cy [Department of Biological Sciences, University of Cyprus, University Campus, P.O. Box 20537, 1678 Nicosia (Cyprus)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Spiral artery (SA) wall remodeling (SAR) is ill-defined and clinically important. Black-Right-Pointing-Pointer SA muscular phenotype prior to and during SAR in mice is underexplored. Black-Right-Pointing-Pointer SA muscular wall consists of contractile and non-contractile components. Black-Right-Pointing-Pointer SA wall non-contractile component may be synthetic smooth muscle. Black-Right-Pointing-Pointer Timing and extent of SA wall contractile component loss is revealed. -- Abstract: During pregnancy the walls of decidual spiral arteries (SAs) undergo clinically important structural modifications crucial for embryo survival/growth and maternal health. However, the mechanisms of SA remodeling (SAR) are poorly understood. Although an important prerequisite to this understanding is knowledge about the phenotype of SA muscular wall prior to and during the beginning of mouse SAR, this remains largely unexplored and was the main aim of this work. Using histological and immunohistochemical techniques, this study shows for the first time that during early mouse gestation, from embryonic day 7.5 (E7.5) to E10.5, the decidual SA muscular coat is not a homogeneous structure, but consists of two concentric layers. The first is a largely one cell-thick sub-endothelial layer of contractile mural cells (positive for {alpha}-smooth muscle actin, calponin and SM22{alpha}) with pericyte characteristics (NG2 positive). The second layer is thicker, and evidence is presented that it may be of the synthetic/proliferative smooth muscle phenotype, based on absence ({alpha}-smooth muscle actin and calponin) or weak (SM22{alpha}) expression of contractile mural cell markers, and presence of synthetic smooth muscle characteristics (expression of non-muscle Myosin heavy chain-IIA and of the cell proliferation marker PCNA). Importantly, immunohistochemistry and morphometrics showed that the contractile mural cell layer although prominent at E7.5-E8

  1. Early Onset Inflammation in Pre-Insulin-Resistant Diet-Induced Obese Rats Does Not Affect the Vasoreactivity of Isolated Small Mesenteric Arteries

    DEFF Research Database (Denmark)

    Blædel, Martin; Raun, Kirsten; Boonen, Harrie C M

    2012-01-01

    Background: Obesity is an increasing burden affecting developed and emerging societies since it is associated with an increased risk of diabetes and consequent cardiovascular complications. Increasing evidence points towards a pivotal role of inflammation in the etiology of vascular dysfunction....... Our study aimed to investigate signs of inflammation and their relation to vascular dysfunction in rats receiving a high fat diet. Methods: Diet-induced obese (DIO) rats were used as a model since these rats exhibit a human pre-diabetic pathology. Oral glucose and insulin tolerance tests were...... concomitant vascular dysfunction. The results show that inflammation and obesity are tightly associated, and that inflammation is manifested prior to significant insulin resistance and vascular dysfunction....

  2. Vertebral Artery Stump Syndrome.

    Science.gov (United States)

    Suzuki, Masato; Dembo, Tomohisa; Hara, Wataru; Tajima, Takashi; Yamashita, Minako; Oji, Satoru; Nomura, Kyoichi

    2018-03-01

    Carotid stump syndrome is a well-documented embolic source for ischemic stroke. However, few cases have been reported of a similar condition - termed vertebral artery stump syndrome - which affects the posterior circulation after vertebral artery origin occlusion. We herein report a case of infarction of the right superior cerebellar artery and left posterior inferior cerebellar artery territories due to vertebral artery stump syndrome. In this interesting case, a turbulent flow at the distal side of the vertebral artery occlusion was captured on ultrasonography, and was identified as the probable mechanism of vertebral artery stump syndrome.

  3. A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics.

    Science.gov (United States)

    Coccarelli, Alberto; Edwards, David Hughes; Aggarwal, Ankush; Nithiarasu, Perumal; Parthimos, Dimitris

    2018-02-01

    Arterial wall dynamics arise from the synergy of passive mechano-elastic properties of the vascular tissue and the active contractile behaviour of smooth muscle cells (SMCs) that form the media layer of vessels. We have developed a computational framework that incorporates both these components to account for vascular responses to mechanical and pharmacological stimuli. To validate the proposed framework and demonstrate its potential for testing hypotheses on the pathogenesis of vascular disease, we have employed a number of pharmacological probes that modulate the arterial wall contractile machinery by selectively inhibiting a range of intracellular signalling pathways. Experimental probes used on ring segments from the rabbit central ear artery are: phenylephrine, a selective α 1-adrenergic receptor agonist that induces vasoconstriction; cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase; and ryanodine, a diterpenoid that modulates Ca 2+ release from the sarcoplasmic reticulum. These interventions were able to delineate the role of membrane versus intracellular signalling, previously identified as main factors in smooth muscle contraction and the generation of vessel tone. Each SMC was modelled by a system of nonlinear differential equations that account for intracellular ionic signalling, and in particular Ca 2+ dynamics. Cytosolic Ca 2+ concentrations formed the catalytic input to a cross-bridge kinetics model. Contractile output from these cellular components forms the input to the finite-element model of the arterial rings under isometric conditions that reproduces the experimental conditions. The model does not account for the role of the endothelium, as the nitric oxide production was suppressed by the action of L-NAME, and also due to the absence of shear stress on the arterial ring, as the experimental set-up did not involve flow. Simulations generated by the integrated model closely matched experimental

  4. The run-off resistance (ROR) assessed on MR angiograms may serve as a valid scoring system in patients with symptomatic peripheral arterial disease (PAD) and correlates with the ankle-brachial pressure index (ABI).

    Science.gov (United States)

    Gorny, O; Santner, W; Fraedrich, G; Jaschke, W; Greiner, A; Schocke, M F

    2012-06-01

    To investigate the correlation between the hemodynamic parameter ankle-brachial pressure index (ABI) and the run-off resistance (ROR) assessed on MR angiograms (MRA) in patients with peripheral arterial disease (PAD) Fontaine Stage I and II and its potential as reliable reporting system in clinical routine. Contrast-enhanced MRA was performed in 321 PAD patients using a 1.5T MR scanner with moving bed technique. The ROR and resting ABI were determined in each patient's leg and correlation analysis was performed using the Pearson test. A significant negative correlation (r = -.513; pROR (mean 11.03±5.42) and resting ABI (mean .81±.26) was identified. An even more pronounced correlation was found in patients younger than median age who had higher ABI values (r = -.608; pROR scoring system evaluated in this series correlates better with the ABI than previously published scoring systems and could be suggested as reporting system for routine MRA evaluation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. The run-off resistance (ROR) assessed on MR angiograms may serve as a valid scoring system in patients with symptomatic peripheral arterial disease (PAD) and correlates with the ankle-brachial pressure index (ABI)

    International Nuclear Information System (INIS)

    Gorny, O.; Santner, W.; Fraedrich, G.; Jaschke, W.; Greiner, A.; Schocke, M.F.

    2012-01-01

    Objective: To investigate the correlation between the hemodynamic parameter ankle-brachial pressure index (ABI) and the run-off resistance (ROR) assessed on MR angiograms (MRA) in patients with peripheral arterial disease (PAD) Fontaine Stage I and II and its potential as reliable reporting system in clinical routine. Methods: Contrast-enhanced MRA was performed in 321 PAD patients using a 1.5 T MR scanner with moving bed technique. The ROR and resting ABI were determined in each patient's leg and correlation analysis was performed using the Pearson test. Results: A significant negative correlation (r = −.513; p < .001) between ROR (mean 11.03 ± 5.42) and resting ABI (mean .81 ± .26) was identified. An even more pronounced correlation was found in patients younger than median age who had higher ABI values (r = −.608; p < .001). Conclusion: The ROR scoring system evaluated in this series correlates better with the ABI than previously published scoring systems and could be suggested as reporting system for routine MRA evaluation.

  6. Altered Daytime Fluctuation Pattern of Plasminogen Activator Inhibitor 1 in Type 2 Diabetes Patients with Coronary Artery Disease: A Strong Association with Persistently Elevated Plasma Insulin, Increased Insulin Resistance, and Abdominal Obesity

    Directory of Open Access Journals (Sweden)

    Katarina Lalić

    2015-01-01

    Full Text Available This study was aimed at investigating daily fluctuation of PAI-1 levels in relation to insulin resistance (IR and daily profile of plasma insulin and glucose levels in 26 type 2 diabetic (T2D patients with coronary artery disease (CAD (group A, 10 T2D patients without CAD (group B, 12 nondiabetics with CAD (group C, and 12 healthy controls (group D. The percentage of PAI-1 decrease was lower in group A versus group B (4.4 ± 2.7 versus 35.0 ± 5.4%; P<0.05 and in C versus D (14.0 ± 5.8 versus 44.7 ± 3.1%; P<0.001. HOMA-IR was higher in group A versus group B (P<0.05 and in C versus D (P<0.01. Simultaneously, AUCs of PAI-1 and insulin were higher in group A versus group B (P<0.05 and in C versus D (P<0.01, while AUC of glucose did not differ between groups. In multiple regression analysis waist-to-hip ratio and AUC of insulin were independent determinants of decrease in PAI-1. The altered diurnal fluctuation of PAI-1, especially in T2D with CAD, might be strongly influenced by a prolonged exposure to hyperinsulinemia in the settings of increased IR and abdominal obesity, facilitating altogether an accelerated atherosclerosis.

  7. A device for rapid and quantitative measurement of cardiac myocyte contractility

    Science.gov (United States)

    Gaitas, Angelo; Malhotra, Ricky; Li, Tao; Herron, Todd; Jalife, José

    2015-03-01

    Cardiac contractility is the hallmark of cardiac function and is a predictor of healthy or diseased cardiac muscle. Despite advancements over the last two decades, the techniques and tools available to cardiovascular scientists are limited in their utility to accurately and reliably measure the amplitude and frequency of cardiomyocyte contractions. Isometric force measurements in the past have entailed cumbersome attachment of isolated and permeabilized cardiomyocytes to a force transducer followed by measurements of sarcomere lengths under conditions of submaximal and maximal Ca2+ activation. These techniques have the inherent disadvantages of being labor intensive and costly. We have engineered a micro-machined cantilever sensor with an embedded deflection-sensing element that, in preliminary experiments, has demonstrated to reliably measure cardiac cell contractions in real-time. Here, we describe this new bioengineering tool with applicability in the cardiovascular research field to effectively and reliably measure cardiac cell contractility in a quantitative manner. We measured contractility in both primary neonatal rat heart cardiomyocyte monolayers that demonstrated a beat frequency of 3 Hz as well as human embryonic stem cell-derived cardiomyocytes with a contractile frequency of about 1 Hz. We also employed the β-adrenergic agonist isoproterenol (100 nmol l-1) and observed that our cantilever demonstrated high sensitivity in detecting subtle changes in both chronotropic and inotropic responses of monolayers. This report describes the utility of our micro-device in both basic cardiovascular research as well as in small molecule drug discovery to monitor cardiac cell contractions.

  8. Hydrogen ion changes and contractile behavior in the perfused rat heart

    NARCIS (Netherlands)

    Cingolani, H.E.; Maas, A.H.J.; Zimmerman, A.N.E.; Meijler, F.L.

    1975-01-01

    The effect of acid-base alterations was analyzed using isolated rat hearts perfused at constant coronary perfusion pressure, and stimulated to contract at constant rate. The amount of shortening in the major axis and its derivative were measured to assess myocardial contractility. Both the

  9. Clinical comparison of bladder contractility parameters calculated from isometric contractions and pressure-flow studies

    NARCIS (Netherlands)

    R. van Mastrigt (Ron); D.J. Griffiths (Derek)

    1987-01-01

    textabstractParameters describing the contractility of the urinary bladder can be calculated from both isometric contractions and pressure-flow studies. The first method has the advantage of making very little demand either on the patient or on the urodynamicist, and the disadvantage of yielding a

  10. Transforming growth factor-beta 1 specifically induce proteins involved in the myofibroblast contractile apparatus

    DEFF Research Database (Denmark)

    Malmström, Johan; Lindberg, Henrik Have; Lindberg, Claes

    2004-01-01

    is to participate in the depolymerization and stabilization of the microfilaments. These results show that TGF-beta(1) induces not only alpha-SMA but a whole set of actin-associated proteins that may contribute to the increased contractile properties of the myofibroblast. These proteins accompany the induced...

  11. Contractile speed and fatigue of adductor pollicis muscle in multiple sclerosis.

    NARCIS (Netherlands)

    Ruiter, C.J. de; Jongen, P.J.H.; Woude, L.H.V. van der; Haan, A. de

    2001-01-01

    The purpose of the study was to investigate differences in contractile speed, force, and fatigability of the adductor pollicis muscle between 12 patients with multiple sclerosis (MS) and 8 sedentary control subjects matched for age and gender. There were no differences between the patients with MS

  12. Contractile speed and fatigue of adductor pollicis muscle in multiple sclerosis

    NARCIS (Netherlands)

    de Ruiter, C.J.; Jongen, P.J.H.; van der Woude, L.H.V.; de Haan, A.

    2001-01-01

    The purpose of the study was to investigate differences in contractile speed, force, and fatigability of the adductor pollicis muscle between 12 patients with multiple sclerosis (MS) and 8 sedentary control subjects matched for age and gender. There were no differences between the patients with MS

  13. Analysis of Contractility and Invasion Potential of Two Canine Mammary Tumor Cell Lines

    Directory of Open Access Journals (Sweden)

    Kaisa Rajakylä

    2017-09-01

    Full Text Available Cancer cells are surrounded by a mechanically and biochemically distinct microenvironment that undergoes dynamic changes throughout the neoplastic progression. During this progression, some cancer cells acquire abnormal characteristics that potentiate their escape from the primary tumor site, to establish secondary tumors in distant organs. Recent studies with several human cancer cell lines have shown that the altered physical properties of tumor cells, such as their ability to apply high traction forces to the surroundings, are directly linked with their potential to invade and metastasize. To test the hypothetical interconnection between actomyosin-mediated traction forces and invasion potential within 3D-microenvironment, we utilized two canine mammary tumor cell lines with different contractile properties. These cell lines, canine mammary tumor (CMT-U27 and CMT-U309, were found to have distinct expression patterns of lineage-specific markers and organization of actin-based structures. In particular, CMT-U309 carcinoma cells were typified by thick contractile actomyosin bundles that exerted high forces to their environment, as measured by traction force microscopy. These high contractile forces also correlated with the prominent invasiveness of the CMT-U309 cell line. Furthermore, we found high contractility and 3D-invasion potential to be dependent on the activity of 5′AMP-activated protein kinase (AMPK, as blocking AMPK signaling was found to reverse both of these features. Taken together, our findings implicate that actomyosin forces correlate with the invasion potential of the studied cell lines.

  14. Effects of Myocardial Contractility on Microemboli Production by Mechanical Heart Valves in a Bovine Model

    OpenAIRE

    Deklunder, Ghislaine; Lecroart, Jean-Louis; Conger, Jeff L.; Lapeyre, Didier; Gregoric, Igor; Rose, Harris; Tamez, Daniel; Frazier, O. H.

    2000-01-01

    Microemboli caused by mechanical heart valves have the potential to cause cerebrovascular events. We investigated the effects of myocardial contractility and heart rate on microemboli production in association with conventional and experimental mechanical heart valves implanted in the mitral position in a bovine model.

  15. Four days of muscle disuse impairs single fiber contractile function in young and old healthy men

    DEFF Research Database (Denmark)

    Hvid, Lars G; Suetta, Charlotte; Aagaard, Per

    2013-01-01

    The purpose of the study was to investigate the effects of 4days of disuse (knee brace) on contractile function of isolated vastus lateralis fibers (n=486) from 11 young (24.3±0.9yrs) and 11 old (67.2±1.0yrs) healthy men having comparable levels of physical activity. Prior to disuse single fiber...

  16. Transient impairments in single muscle fibre contractile function after prolonged cycling in elite endurance athletes

    DEFF Research Database (Denmark)

    Hvid, L G; Gejl, Kasper Degn; Bech, R D

    2013-01-01

    Prolonged muscle activity impairs whole-muscle performance and function. However, little is known about the effects of prolonged muscle activity on the contractile function of human single muscle fibres. The purpose of this study was to investigate the effects of prolonged exercise and subsequent...

  17. Chronic clenbuterol treatment compromises force production without directly altering skeletal muscle contractile machinery.

    Science.gov (United States)

    Py, G; Ramonatxo, C; Sirvent, P; Sanchez, A M J; Philippe, A G; Douillard, A; Galbès, O; Lionne, C; Bonnieu, A; Chopard, A; Cazorla, O; Lacampagne, A; Candau, R B

    2015-04-15

    Clenbuterol is a β2 -adrenergic receptor agonist known to induce skeletal muscle hypertrophy and a slow-to-fast phenotypic shift. The aim of the present study was to test the effects of chronic clenbuterol treatment on contractile efficiency and explore the underlying mechanisms, i.e. the muscle contractile machinery and calcium-handling ability. Forty-three 6-week-old male Wistar rats were randomly allocated to one of six groups that were treated with either subcutaneous equimolar doses of clenbuterol (4 mg kg(-1) day(-1) ) or saline solution for 9, 14 or 21 days. In addition to the muscle hypertrophy, although an 89% increase in absolute maximal tetanic force (Po ) was noted, specific maximal tetanic force (sPo) was unchanged or even depressed in the slow twitch muscle of the clenbuterol-treated rats (P clenbuterol treatment significantly reduced the rate constant of force development and the slow and fast rate constants of relaxation in extensor digitorum longus muscle (P clenbuterol-treated animals demonstrated decreased amplitude after 14 days (-19%, P clenbuterol treatment reduces contractile efficiency, with altered contraction and relaxation kinetics, but without directly altering the contractile machinery. Lower Ca(2+) release during contraction could partially explain these deleterious effects. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  18. In vitro contractile effects of agents used in the clinical management of postpartum haemorrhage.

    Science.gov (United States)

    Morrison, John J; Crosby, David A; Crankshaw, Denis J

    2016-10-15

    Uterine atony is a major cause of postpartum haemorrhage and maternal mortality. However, the comparative pharmacology of agents used to treat this condition is poorly understood. This study evaluates, using human pregnant myometrium in vitro, a range of contractile parameters for agents used in the clinical treatment of atonic postpartum haemorrhage. The effects of oxytocin, carbetocin, ergometrine, carboprost, syntometrine and misoprostol were investigated in 146 myometrial strips from 19 donors. The potency and maximal response values were obtained, and compared, using both maximal amplitude and mean contractile force as indices of contraction. Single, EC50 concentrations of the agents were administered and both force and contraction peak parameters were compared during a 15-min exposure. Differences were considered significant when Poxytocin and carbetocin being the most potent. The most important difference between the agents was in their ability to increase the mean contractile force, with oxytocin superior to all agents except syntometrine. In single dose experiments, mean contractile force was the parameter that separated the agents. In this respect, oxytocin was not statistically different from carboprost or syntometrine, but was superior to all other agents. These findings support a clear role for oxytocin as the first line agent for treatment of postpartum haemorrhage and raise doubts about the potential clinical usefulness of misoprostol. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Changes in muscle size and MHC composition in response to resistance exercise with heavy and light loading intensity

    DEFF Research Database (Denmark)

    Holm, L.; Reitelseder, S.; Pedersen, T.G.

    2008-01-01

    Muscle mass accretion is accomplished by heavy-load resistance training. The effect of light-load resistance exercise has been far more sparsely investigated with regard to potential effect on muscle size and contractile strength. We applied a resistance exercise protocol in which the same indivi...

  20. Dynamic MR cholangiography after fatty meal loading. Cystic contractility and dynamic evaluation of biliary stasis

    International Nuclear Information System (INIS)

    Omata, Takayuki; Saito, Kazuhiro; Kotake, Fumio; Mizokami, Yuji; Matsuoka, Takeshi; Abe, Kimihiko

    2002-01-01

    Dynamic MR cholangiography was conducted on patients with cholelithiasis or choledocholithiasis who had consumed a fatty test meal (Molyork) and the cystic contractility and dynamics of biliary stasis was evaluated. The subjects were 25 with intracystic cholelithiasis, 10 with choledocholithiasis and 10 normal controls. For an imaging sequence, the rapid acquisition with relaxation enhancement (RARE) method was employed and imaging was conducted for 40 min (every 30 s following Molyork administration) without breath-holding. The gallbladder contraction ratio was computed and the contractile ratio for the common bile duct was calculated. To determine the bile flow to the duodenum, the high-intensity signal, indicating the flow from the lower common bile duct, and perfusion of the duodenum were observed in dynamic mode on the monitor with the naked eye and interpreted as positive bile flow. The frequency of this flow was visually monitored. The gallbladder contractile ratio was significantly reduced in patients with cholelithiasis or choledocholithiasis compared with the controls. In a comparison with the normal controls, no sequential changes were noted in the mean contractile ratio of the common bile duct of the patients with cholelithiasis or choledocholithiasis. The mean frequency of bile flow observed for each 40 min period was 13±2.4, 6±2.2, and 4±1.3 times for the controls, those with intracystic cholelithiasis, and those with choledocholithiasis, respectively. Compared with the controls, the latter two patient groups showed evident reductions in the frequency of bile flow to the duodenum (p<0.001). Dynamic MRC combined with Molyork loading makes it possible to compute cystic contractile ratios and perform a dynamic examination of bile flow under non-invasive, near-physiological conditions. (author)

  1. Esophagogastric junction contractile integral (EGJ-CI) quantifies changes in EGJ barrier function with surgical intervention.

    Science.gov (United States)

    Wang, D; Patel, A; Mello, M; Shriver, A; Gyawali, C P

    2016-05-01

    Esophagogastric junction contractile integral (EGJ-CI) assesses EGJ barrier function on esophageal high resolution manometry (HRM). We assessed EGJ-CI values in achalasia and gastroesophageal reflux disease (GERD) to determine if postoperative EGJ-CI changes reflected surgical intervention. Twenty-one achalasia patients (42.8 ± 3.2 years, 62% F) with HRM before and after Heller myotomy (HM) and 68 GERD patients (53.9 ± 1.8 years, 66% F) undergoing antireflux surgery (ARS) were compared to 21 healthy controls (27.6 ± 0.6 years, 52% F). Esophagogastric junction contractile integral (mmHg.cm) was calculated using the distal contractile integral measurement across the EGJ, measured above the gastric baseline and corrected for respiration. Pre and postsurgical EGJ-CI and conventional lower esophageal sphincter pressure (LESP) metrics were compared within and between these groups using non-parametric tests. Correlation between EGJ-CI and conventional LESP metrics was assessed. Baseline EGJ-CI was higher in achalasia compared to GERD (p integral declined by 59.2% after HM in achalasia (p = 0.001), and increased by 26.3% after ARS in GERD (p = 0.005). End-expiratory and basal LESP decreased by 74.5% and 64.5% with HM, but increased by only 17.8% and 4.3% with ARS. Differences were noted between Dor vs Toupet fundoplication in achalasia (p = 0.007), and partial vs complete ARS in GERD (p = 0.03). Esophagogastric junction contractile integral correlated modestly with both end-expiratory and basal LESP (Pearson's r of 0.8 for all), but was less robust in GERD (0.7). Esophagogastric junction contractile integral has clinical utility in assessing EGJ barrier function at baseline and after surgical intervention to the EGJ, and could complement conventional EGJ metrics. © 2016 John Wiley & Sons Ltd.

  2. Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

    Energy Technology Data Exchange (ETDEWEB)

    Morton, M.J., E-mail: michael.morton@astrazeneca.com [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Armstrong, D.; Abi Gerges, N. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Bridgland-Taylor, M. [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Pollard, C.E.; Bowes, J.; Valentin, J.-P. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom)

    2014-09-01

    Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility.

  3. Dynamic MR cholangiography after fatty meal loading. Cystic contractility and dynamic evaluation of biliary stasis

    Energy Technology Data Exchange (ETDEWEB)

    Omata, Takayuki; Saito, Kazuhiro; Kotake, Fumio; Mizokami, Yuji; Matsuoka, Takeshi; Abe, Kimihiko [Tokyo Medical Coll., Ami, Ibaraki (Japan). Kasumigaura Hospital

    2002-07-01

    Dynamic MR cholangiography was conducted on patients with cholelithiasis or choledocholithiasis who had consumed a fatty test meal (Molyork) and the cystic contractility and dynamics of biliary stasis was evaluated. The subjects were 25 with intracystic cholelithiasis, 10 with choledocholithiasis and 10 normal controls. For an imaging sequence, the rapid acquisition with relaxation enhancement (RARE) method was employed and imaging was conducted for 40 min (every 30 s following Molyork administration) without breath-holding. The gallbladder contraction ratio was computed and the contractile ratio for the common bile duct was calculated. To determine the bile flow to the duodenum, the high-intensity signal, indicating the flow from the lower common bile duct, and perfusion of the duodenum were observed in dynamic mode on the monitor with the naked eye and interpreted as positive bile flow. The frequency of this flow was visually monitored. The gallbladder contractile ratio was significantly reduced in patients with cholelithiasis or choledocholithiasis compared with the controls. In a comparison with the normal controls, no sequential changes were noted in the mean contractile ratio of the common bile duct of the patients with cholelithiasis or choledocholithiasis. The mean frequency of bile flow observed for each 40 min period was 13{+-}2.4, 6{+-}2.2, and 4{+-}1.3 times for the controls, those with intracystic cholelithiasis, and those with choledocholithiasis, respectively. Compared with the controls, the latter two patient groups showed evident reductions in the frequency of bile flow to the duodenum (p<0.001). Dynamic MRC combined with Molyork loading makes it possible to compute cystic contractile ratios and perform a dynamic examination of bile flow under non-invasive, near-physiological conditions. (author)

  4. PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic signaling

    Science.gov (United States)

    Yang, Jason H.; Polanowska-Grabowska, Renata K.; Smith, Jeffrey S.; Shields, Charles W.; Saucerman, Jeffrey J.

    2014-01-01

    β-adrenergic signaling is spatiotemporally heterogeneous in the cardiac myocyte, conferring exquisite control to sympathetic stimulation. Such heterogeneity drives the formation of protein kinase A (PKA) signaling microdomains, which regulate Ca2+ handling and contractility. Here, we test the hypothesis that the nucleus independently comprises a PKA signaling microdomain regulating myocyte hypertrophy. Spatially-targeted FRET reporters for PKA activity identified slower PKA activation and lower isoproterenol sensitivity in the nucleus (t50 = 10.60±0.68 min; EC50 = 89.00 nmol/L) than in the cytosol (t50 = 3.71±0.25 min; EC50 = 1.22 nmol/L). These differences were not explained by cAMP or AKAP-based compartmentation. A computational model of cytosolic and nuclear PKA activity was developed and predicted that differences in nuclear PKA dynamics and magnitude are regulated by slow PKA catalytic subunit diffusion, while differences in isoproterenol sensitivity are regulated by nuclear expression of protein kinase inhibitor (PKI). These were validated by FRET and immunofluorescence. The model also predicted differential phosphorylation of PKA substrates regulating cell contractility and hypertrophy. Ca2+ and cell hypertrophy measurements validated these predictions and identified higher isoproterenol sensitivity for contractile enhancements (EC50 = 1.84 nmol/L) over cell hypertrophy (EC50 = 85.88 nmol/L). Over-expression of spatially targeted PKA catalytic subunit to the cytosol or nucleus enhanced contractile and hypertrophic responses, respectively. We conclude that restricted PKA catalytic subunit diffusion is an important PKA compartmentation mechanism and the nucleus comprises a novel PKA signaling microdomain, insulating hypertrophic from contractile β-adrenergic signaling responses. PMID:24225179

  5. An Acanthamoeba castellanii metacaspase associates with the contractile vacuole and functions in osmoregulation.

    Science.gov (United States)

    Saheb, Entsar; Trzyna, Wendy; Bush, John

    2013-03-01

    Acanthamoeba castellanii is a free-living protozoan. Some strains are opportunistic pathogens. A type-I metacaspase was identified in A. castellanii (Acmcp) and was shown to be expressed through the encystation process. The model organism, Dictyostelium discoideum, has been used here as a model for studying these caspase-like proteins. Separate cell lines expressing a GFP-tagged version of the full length Acmcp protein, as well as a deletion proline region mutant of Acmcp protein (GFP-Acmcp-dpr), have been introduced into D. discoideum. Both mutants affect the cellular metabolism, characterized by an increase in the growth rate. Microscopic imaging revealed an association between Acmcp and the contractile vacuole system in D. discoideum. The treatment of cells with selected inhibitors in different environments added additional support to these findings. This evidence shows that Acmcp plays an important role in contractile vacuole regulation and mediated membrane trafficking in D. discoideum. Additionally, the severe defect in contractile vacuole function in GFP-Acmcp-dpr mutant cells suggests that the proline-rich region in Acmcp has an essential role in binding this protein with other partners to maintain this process. Furthermore, Yeast two-hybrid system identified there are weak interactions of the Dictyostelium contractile vacuolar proteins, including Calmodulin, RabD, Rab11 and vacuolar proton ATPase, with Acmcp protein. Taken together, our findings suggest that A. castellanii metacaspase associate with the contractile vacuole and have an essential role in cell osmoregulation, which contributes to its attractiveness as a possible target for treatment therapies against A. castellanii infection. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Effect of Agonist and Antagonist on the In Vitro Contractility of Inflamed Vermiform Appendix.

    Science.gov (United States)

    Singh, Phani Bhushan; Tiwary, Pushpakant; Singh, Sanjeev K; Pandey, Ratna; Roy, Atanu; Kar, Amrita Ghosh; Basu, Somprakas; Tiwari, Anil Kumar

    2017-06-01

    Appendicitis poses a great health problem worldwide. Previous studies demonstrated structural damage to neuronal network and interstitial cell of Cajal in appendicitis. Above observations suggest for the alterations in appendicular motility/contractility in appendicitis. But the mechanisms involved in mediating the contractility in inflamed vermiform appendix is not known till date. The present in vitro study was performed to find out the mechanisms responsible for contractility in the inflamed human vermiform appendix. Contractions of the longitudinal muscle strips of inflamed appendix were recorded in vitro at 37±0.5°C. Control contractions were recorded for 30 min after an initial tension of 0.5 gram. Initially dose-response experiments of agonists (acetylcholine, serotonin and histamine) were performed separately and the dose that produced maximum contraction was determined with each agonist. This maximal dose of agonist was used to elicit contractions in next series of experiments before and after pre-treatment with appropriate antagonists like atropine, ondansetron (5-HT 3 antagonist) and chlorpheniramine maleate respectively. Acetylcholine (ACh) and serotonin (5-HT) elicited maximum amplitude of contraction at 10 µM and 1 µM concentration respectively. These contractions were significantly blocked by prior exposure of muscle strips with atropine (100 µM) and ondansetron (10 µM). Histamine produced very low amplitude of contractions in comparison to ACh or 5-HT and did not exhibit dose-response relations. The histamine induced contractions were blocked by H 1 antagonist chlorpheniramine maleate (100 µM). The observations suggested that the contractility of longitudinal muscle strips of inflamed vermiform appendix in human beings was predominantly mediated by muscarinic and serotonergic (5-HT 3 ) mechanisms, whereas, histaminergic mechanisms played a minor role in mediating the contractility.

  7. Monitorização ambulatorial da pressão arterial e risco cardiovascular em mulheres com hipertensão resistente Monitoreo ambulatorio de la presión Arterial y riesgo cardiovascular en mujeres con hipertensión resistente Ambulatory blood pressure monitoring and cardiovascular risk in resistant hypertensive women

    Directory of Open Access Journals (Sweden)

    Monica Maria Ferreira Magnanini

    2009-06-01

    Full Text Available FUNDAMENTO: Poucos estudos exploraram o valor prognóstico da monitorização ambulatorial da pressão arterial (MAPA em pacientes hipertensos resistentes, um grupo que apresenta alto risco. OBJETIVO: Investigar o valor prognóstico da pressão arterial (PA de vigília, em mulheres hipertensas resistentes. MÉTODOS: Foram acompanhadas por até 8,9 anos (média 3,9, 382 mulheres hipertensas resistentes com idade entre 24-92 anos, atendidas em uma unidade de hipertensão de um hospital universitário. As pacientes foram classificadas como controladas (PA de consultório > 140/90 mmHg e PA de vigília 140/90 mmHg e PA de vigília > 135/85 mmHg. Analisou-se uma combinação de mortalidade cardiovascular, cardiopatia isquêmica, acidente vascular encefálico e nefropatia. Utilizou-se o modelo proporcional de Cox para estimar o risco de eventos cardiovasculares ajustado para potenciais confundidores. RESULTADOS: A taxa total de eventos foi de 5,0 por 100 mulheres-ano. No grupo de controladas esse valor foi de 3,7 e entre as não-controladas, de 5,8, com p=0.06. Os riscos relativos associados ao aumento de 10 mmHg na PA sistólica, ajustando para idade e tabagismo atual, foram maiores que os associados a aumentos de 5 mmHg na PA diastólica. Pacientes com descenso noturno 10%, embora essa associação não tenha sido estatisticamente significante. A pressão de vigília não controlada (sim/não foi um forte fator de risco independente, 1,67 (1,00-2,78. CONCLUSÃO: O aumento de 67% no risco de evento cardiovascular quando a PA de vigília não estava controlada é indicador de que o uso da MAPA é essencial na avaliação do controle e como guia das decisões terapêuticas na hipertensão resistente.FUNDAMENTO: Pocos estudios exploraron el valor pronóstico del monitoreo ambulatorio de presión arterial (MAPA en pacientes hipertensos resistentes, un grupo que presenta alto riesgo. OBJETIVO: Investigar el valor pronóstico de la presión arterial (PA

  8. Src tyrosine kinases contribute to serotonin-mediated contraction by regulating calcium-dependent pathways in rat skeletal muscle arteries.

    Science.gov (United States)

    Zavaritskaya, Olga; Lubomirov, Lubomir T; Altay, Serdar; Schubert, Rudolf

    2017-06-01

    The Src tyrosine kinase family contributes to the signalling mechanism mediating serotonin (5-hydroxytryptamine (5-HT))-induced vasoconstriction. These kinases were reported to influence the calcium sensitivity of the contractile apparatus. Whether Src kinases affect also the intracellular calcium concentration during constriction of intact arteries is unknown. Thus, we tested the hypothesis that constriction of arteries is associated with a Src kinase-dependent alteration of the intracellular calcium concentration. Contractility of gracilis arteries of Wistar rats was studied using isometric and isobaric myography. The intracellular calcium concentration was measured simultaneously with tension by FURA-2 fluorimetry. Inhibition of Src kinases with 10 μM PP2, 30 μM dasatinib and 100 μM AZM 475271 resulted in a strong attenuation of 5-HT-induced contractions. Vessel incubation with 10 μM PP3, an inactive analogue of PP2, had no effect. Removal of the endothelium did not alter vessel contractile responses to 5-HT nor the action of the Src-kinase inhibitor PP2. The PP2-mediated inhibition of 5-HT-induced contraction was associated with a reduced response of [Ca 2+ ] i to 5-HT. In particular, inhibition of Src kinases attenuates 5-HT-induced calcium influx as well as calcium release from intracellular stores. In contrast, the calcium sensitivity of the contractile apparatus and the filling state of the sarcoplasmic reticulum were not influenced by Src kinases during 5-HT-induced contractions. We conclude that Src kinase activation is a powerful mechanism to produce vasoconstriction of small skeletal muscle arteries of rats. This effect is endothelium-independent. The data further suggest that the action of c-Src kinases is associated with a change in the intracellular calcium concentration that involves Ca 2+ entry and Ca 2+ release pathways.

  9. Coronary microvascular dysfunction and myocardial contractile reserve in women with angina and no obstructive coronary artery disease

    DEFF Research Database (Denmark)

    Michelsen, Marie M; Pena, Adam; Mygind, Naja D

    2018-01-01

    BACKGROUND: Coronary microvascular dysfunction (CMD) is a potential cause of myocardial ischemia and may affect myocardial function at rest and during stress. We investigated whether CMD was associated with left ventricular diastolic and systolic function at rest and during pharmacologically......) was measured in 919 women of whom 26% had CMD (defined as CFVR CMD) was associated with higher age and a higher resting heart rate. Women with CMD had a reduced GLS reserve (P = .005), while we found no association between CFVR and LVEF at rest, GLS at rest...... dysfunction measured by echocardiography at rest. CONCLUSION: The GLS reserve was significantly lower in women with CMD. The mechanisms underlying the association between CMD and GLS reserve warrant further study....

  10. Effect of hypoxia on endothelium-dependent relaxation of canine and rabbit basilar arteries.

    Science.gov (United States)

    Nakagomi, T; Kassell, N F; Sasaki, T; Hongo, K; Fujiwara, S; Lehman, R M; Vollmer, D G

    1989-01-01

    An important role of endothelium-dependent relaxation in the local regulation of vascular tone has been suggested. In the present study, the effect of hypoxia on endothelium-dependent relaxation was investigated in canine and rabbit basilar and in rabbit common carotid arteries in vitro, using an isometric tension recording method. Hypoxia was introduced by changing the gas mixture in the in vitro chamber from 95% O2-5% CO2 to 95% N2-5% CO2. Thrombin and acetylcholine were used to induce endothelium-dependent relaxation. Thrombin at 0.1 and 1.0 U/ml, respectively, caused dose-dependent relaxation of the canine basilar artery precontracted by 10(-6)M prostaglandin F2 alpha. Acetylcholine also evoked dose-dependent relaxation of rabbit basilar and common carotid arteries precontracted by serotonin. Under hypoxic conditions, the relaxing effect of thrombin or acetylcholine decreased both in canine and in rabbit arteries, although it was not significant in rabbit basilar arteries. It has been postulated that following subarachnoid haemorrhage, diffusion of oxygen to the walls of the major cerebral arteries might be impaired by the subarachnoid clot. This could cause hypoxia of the arteries and contribute to vasospasm by suppressing endothelium-dependent relaxation, as well as by enhancing the contractile responses of the cerebral arteries to the vasoconstrictor agents in the bloody cerebrospinal fluid.

  11. A new diagnostic approach to popliteal artery entrapment syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Charles; Kennedy, Dominic; Bastian-Jordan, Matthew; Hislop, Matthew; Cramp, Brendan; Dhupelia, Sanjay [Queensland X-Ray, Sunnybank, Queensland, 4109 (Australia)

    2015-09-15

    A new method of diagnosing and defining functional popliteal artery entrapment syndrome is described. By combining ultrasonography and magnetic resonance imaging techniques with dynamic plantarflexion of the ankle against resistance, functional entrapment can be demonstrated and the location of the arterial occlusion identified. This combination of imaging modalities will also define muscular anatomy for guiding intervention such as surgery or Botox injection.

  12. Biventricular Pacing Cardiac Contractility Modulation Improves Cardiac Contractile Function via Upregulating SERCA2 and miR-133 in a Rabbit Model of Congestive Heart Failure

    Directory of Open Access Journals (Sweden)

    Bin Ning

    2014-05-01

    Full Text Available Objective: To compare the effects of biventricular electrical pacing and conventional single-ventricular pacing for cardiac contractility modulation (CCM on cardiac contractile function and to delineate the underlying molecular mechanisms. Methods: Forty rabbits were divided into four groups before surgery: healthy control, HF sham, HF left ventricular pacing CCM (LVP-CCM, and HF biventricular pacing CCM (BVP-CCM groups with n=10 for each group. A rabbit model of chronic heart failure was established by ligating ascending aortic root of rabbits. Then electrical stimulations during the absolute refractory period were delivered to the anterior wall of left ventricle in the LVP-CCM group and on the anterior wall of both left and right ventricles in the BVP-CCM group lasting six hours per day for seven days. Changes in ventricular structure, cardiac function and electrocardiogram were monitored before and after CCM stimulation. Results: Compared with the sham-operated group, heart weight, heart weight index, LV end-systolic diameter (LVESD, LV end-diastolic diameter (LVEDD in the LVP-CCM and BVP-CCM groups were significantly decreased (ppp2+-ATPase (SERCA2a protein levels were upregulated by 1.7 and 2.4 fold, along with simultaneous upregulation of a cardiac-enriched microRNA miR-133 levels by 2.6 and 3.3 fold, in LVP-CCM and BVP-CCM, respectively, compared to sham. Conclusions: Biventricular pacing CCM is superior to conventional monoventricular pacing CCM, producing greater improvement cardiac contractile function. Greater upregulation of SERCA2 and miR-133 may account, at least partially, for the improvement by BVP-CCM.

  13. Arterial Wall Properties and Womersley Flow in Fabry Disease

    Directory of Open Access Journals (Sweden)

    Dimitriadis Emilios

    2002-01-01

    Full Text Available Abstract Background Fabry disease is an X-linked recessive lysosomal storage disease resulting in the cellular accumulation of globotriaosylceramide particularly globotriaosylceramide. The disease is characterized by a dilated vasculopathy with arterial ectasia in muscular arteries and arterioles. Previous venous plethysomographic studies suggest enhanced endothelium-dependent vasodilation in Fabry disease indicating a functional abnormality of resistance vessels. Methods We examined the mechanical properties of the radial artery in Fabry disease, a typical fibro-muscular artery. Eight control subjects and seven patients with Fabry disease had a right brachial arterial line placed allowing real time recording of intra-arterial blood pressure. Real time B-mode ultrasound recordings of the right radial artery were obtained simultaneously allowing calculation of the vessel wall internal and external diameter, the incremental Young's modulus and arterial wall thickness. By simultaneously measurement of the distal index finger-pulse oximetry the pulse wave speed was calculated. From the wave speed and the internal radial artery diameter the volume flow was calculated by Womersley analysis following truncation of the late diastolic phase. Results No significant difference was found between Fabry patients and controls for internal or external arterial diameters, the incremental Young's modulus, the arterial wall thickness, the pulse wave speed and the basal radial artery blood flow. Further, no significant difference was found for the radial artery blood flow in response to intra-arterial acetylcholine or sodium nitroprusside. Both drugs however, elevated the mean arterial flow. Conclusions The current study suggests that no structural or mechanical abnormality exists in the vessel wall of fibro-muscular arteries in Fabry disease. This may indicate that a functional abnormality downstream to the conductance vessels is the dominant feature in

  14. Arterial ageing: from endothelial dysfunction to vascular calcification.

    Science.gov (United States)

    Tesauro, M; Mauriello, A; Rovella, V; Annicchiarico-Petruzzelli, M; Cardillo, C; Melino, G; Di Daniele, N

    2017-05-01

    Complex structural and functional changes occur in the arterial system with advancing age. The aged artery is characterized by changes in microRNA expression patterns, autophagy, smooth muscle cell migration and proliferation, and arterial calcification with progressively increased mechanical vessel rigidity and stiffness. With age the vascular smooth muscle cells modify their phenotype from contractile to 'synthetic' determining the development of intimal thickening as early as the second decade of life as an adaptive response to forces acting on the arterial wall. The increased permeability observed in intimal thickening could represent the substrate on which low-level atherosclerotic stimuli can promote the development of advanced atherosclerotic lesions. In elderly patients the atherosclerotic plaques tend to be larger with increased vascular stenosis. In these plaques there is a progressive accumulation of both lipids and collagen and a decrease of inflammation. Similarly the plaques from elderly patients show more calcification as compared with those from younger patients. The coronary artery calcium score is a well-established marker of adverse cardiovascular outcomes. The presence of diffuse calcification in a severely stenotic segment probably induces changes in mechanical properties and shear stress of the arterial wall favouring the rupture of a vulnerable lesion in a less stenotic adjacent segment. Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing-related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  15. GPER Mediates Functional Endothelial Aging in Renal Arteries.

    Science.gov (United States)

    Meyer, Matthias R; Rosemann, Thomas; Barton, Matthias; Prossnitz, Eric R

    2017-01-01

    Aging is associated with impaired renal artery function, which is partly characterized by arterial stiffening and a reduced vasodilatory capacity due to excessive generation of reactive oxygen species by NADPH oxidases (Nox). The abundance and activity of Nox depends on basal activity of the heptahelical transmembrane receptor GPER; however, whether GPER contributes to age-dependent functional changes in renal arteries is unknown. This study investigated the effect of aging and Nox activity on renal artery tone in wild-type and GPER-deficient (Gper-/-) mice (4 and 24 months old). In wild-type mice, aging markedly impaired endothelium-dependent, nitric oxide (NO)-mediated relaxations to acetylcholine, which were largely preserved in renal arteries of aged Gper-/- mice. The Nox inhibitor gp91ds-tat abolished this difference by greatly enhancing relaxations in wild-type mice, while having no effect in Gper-/- mice. Contractions to angiotensin II and phenylephrine in wild-type mice were partly sensitive to gp91ds-tat but unaffected by aging. Again, deletion of GPER abolished effects of Nox inhibition on contractile responses. In conclusion, basal activity of GPER is required for the age-dependent impairment of endothelium-dependent, NO-mediated relaxation in the renal artery. Restoration of relaxation by a Nox inhibitor in aged wild-type but not Gper-/- mice strongly supports a role for Nox-derived reactive oxygen species as the underlying cause. Pharmacological blockers of GPER signaling may thus be suitable to inhibit functional endothelial aging of renal arteries by reducing Nox-derived oxidative stress and, possibly, the associated age-dependent deterioration of kidney function. © 2017 S. Karger AG, Basel.

  16. Quantitative circumferential strain analysis using adenosine triphosphate-stress/rest 3-T tagged magnetic resonance to evaluate regional contractile dysfunction in ischemic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Masashi, E-mail: m.nakamura1230@gmail.com [Department of Radiology, Ehime University Graduate School of Medicine, Shitsukawa, Toon-city, Ehime 791-0295 (Japan); Kido, Tomoyuki [Department of Radiology, Saiseikai Matsuyama Hospital, Ehime 791-0295 (Japan); Kido, Teruhito; Tanabe, Yuki; Matsuda, Takuya; Nishiyama, Yoshiko; Miyagawa, Masao; Mochizuki, Teruhito [Department of Radiology, Ehime University Graduate School of Medicine, Shitsukawa, Toon-city, Ehime 791-0295 (Japan)

    2015-08-15

    Highlights: • Infarcted segments could be differentiated from non-ischemic and ischemic segments with high sensitivity and specificity under at rest conditions. • The time-to-peak circumferential strain values in infarcted segments were more significantly delayed than those in non-ischemic and ischemic segments. • Both circumferential strain and circumferential systolic strain rate values under ATP-stress conditions were significantly lower in ischemic segments than in non-ischemic segments. • Subtracting stress and rest circumferential strain had a higher diagnostic capability for ischemia relative to only utilizing rest or ATP-stress circumferential strain values. • A circumferential strain analysis using tagged MR can quantitatively assess contractile dysfunction in ischemic and infarcted myocardium. - Abstract: Purpose: We evaluated whether a quantitative circumferential strain (CS) analysis using adenosine triphosphate (ATP)-stress/rest 3-T tagged magnetic resonance (MR) imaging can depict myocardial ischemia as contractile dysfunction during stress in patients with suspected coronary artery disease (CAD). We evaluated whether it can differentiate between non-ischemia, myocardial ischemia, and infarction. We assessed its diagnostic performance in comparison with ATP-stress myocardial perfusion MR and late gadolinium enhancement (LGE)-MR imaging. Methods: In 38 patients suspected of having CAD, myocardial segments were categorized as non-ischemic (n = 485), ischemic (n = 74), or infarcted (n = 49) from the results of perfusion MR and LGE-MR. The peak negative CS value, peak circumferential systolic strain rate (CSR), and time-to-peak CS were measured in 16 segments. Results: A cutoff value of −12.0% for CS at rest allowed differentiation between infarcted and other segments with a sensitivity of 79%, specificity of 76%, accuracy of 76%, and an area under the curve (AUC) of 0.81. Additionally, a cutoff value of 477.3 ms for time-to-peak CS at rest

  17. Obesity Induces Artery-Specific Alterations: Evaluation of Vascular Function and Inflammatory and Smooth Muscle Phenotypic Markers

    Directory of Open Access Journals (Sweden)

    Antonio Garcia Soares

    2017-01-01

    Full Text Available Vascular alterations are expected to occur in obese individuals but the impact of obesity could be different depending on the artery type. We aimed to evaluate the obesity effects on the relaxing and contractile responses and inflammatory and smooth muscle (SM phenotypic markers in two vascular beds. Obesity was induced in C57Bl/6 mice by 16-week high-fat diet and vascular reactivity, mRNA expression of inflammatory and SM phenotypic markers, and collagen deposition were evaluated in small mesenteric arteries (SMA and thoracic aorta (TA. Endothelium-dependent relaxation in SMA and TA was not modified by obesity. In contrast, contraction induced by depolarization and contractile agonists was reduced in SMA, whereas only contraction induced by adrenergic agonist was reduced in TA of obese mice. Obesity increased the mRNA expression of pro- and anti-inflammatory cytokines in SMA and TA. The expression of genes necessary for maintaining contractile ability was increased by obesity, but the increase was more pronounced in TA. Collagen deposition was increased in SMA, but not in TA, of obese mice. Although the endothelial function was still preserved, the SM of the two artery types was impaired by obesity, but the impairment was higher in SMA, which could be associated with SM phenotypic changes.

  18. Hypoxia-induced glucose-6-phosphate dehydrogenase overexpression and -activation in pulmonary artery smooth muscle cells: implication in pulmonary hypertension

    Science.gov (United States)

    Chettimada, Sukrutha; Gupte, Rakhee; Rawat, Dhwajbahadur; Gebb, Sarah A.; McMurtry, Ivan F.

    2014-01-01

    Severe pulmonary hypertension is a debilitating disease with an alarmingly low 5-yr life expectancy. Hypoxia, one of the causes of pulmonary hypertension, elicits constriction and remodeling of the pulmonary arteries. We now know that pulmonary arterial remodeling is a consequence of hyperplasia and hypertrophy of pulmonary artery smooth muscle (PASM), endothelial, myofibroblast, and stem cells. However, our knowledge about the mechanisms that cause these cells to proliferate and hypertrophy in response to hypoxic stimuli is still incomplete, and, hence, the treatment for severe pulmonary arterial hypertension is inadequate. Here we demonstrate that the activity and expression of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, are increased in hypoxic PASM cells and in lungs of chronic hypoxic rats. G6PD overexpression and -activation is stimulated by H2O2. Increased G6PD activity contributes to PASM cell proliferation by increasing Sp1 and hypoxia-inducible factor 1α (HIF-1α), which directs the cells to synthesize less contractile (myocardin and SM22α) and more proliferative (cyclin A and phospho-histone H3) proteins. G6PD inhibition with dehydroepiandrosterone increased myocardin expression in remodeled pulmonary arteries of moderate and severe pulmonary hypertensive rats. These observations suggest that altered glucose metabolism and G6PD overactivation play a key role in switching the PASM cells from the contractile to synthetic phenotype by increasing Sp1 and HIF-1α, which suppresses myocardin, a key cofactor that maintains smooth muscle cell in contractile state, and increasing hypoxia-induced PASM cell growth, and hence contribute to pulmonary arterial remodeling and pathogenesis of pulmonary hypertension. PMID:25480333

  19. Increased arterial compliance in decompensated cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, Søren; Schifter, S

    1999-01-01

    BACKGROUND/AIMS: In patients with cirrhosis, the systemic circulation is hyperdynamic with low arterial blood pressure and reduced systemic vascular resistance. The present study was undertaken to estimate the compliance of the arterial tree in relation to severity of cirrhosis, circulating level...... of the vasodilator, calcitonin gene-related peptide (CGRP) and mean arterial blood pressure (MAP). METHODS: Arterial compliance (COMPart=deltaV/deltaP) was determined as the stroke volume relative to pulse pressure (i.e. systolic minus diastolic blood pressure) during a haemodynamic evaluation of portal hypertension...... of CGRP (r=0.34, parterial compliance in cirrhosis is directly related to the severity of the disease and to the elevated level of circulating vasodilator peptide CGRP, and inversely related...

  20. Increased arterial compliance in decompensated cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren; Schifter, S

    1999-01-01

    of the vasodilator, calcitonin gene-related peptide (CGRP) and mean arterial blood pressure (MAP). METHODS: Arterial compliance (COMPart=deltaV/deltaP) was determined as the stroke volume relative to pulse pressure (i.e. systolic minus diastolic blood pressure) during a haemodynamic evaluation of portal hypertension......BACKGROUND/AIMS: In patients with cirrhosis, the systemic circulation is hyperdynamic with low arterial blood pressure and reduced systemic vascular resistance. The present study was undertaken to estimate the compliance of the arterial tree in relation to severity of cirrhosis, circulating level...... in patients with biopsy-verified cirrhosis (Child-Turcotte classes A/B/C=10/15/6). RESULTS: COMPart was significantly higher in cirrhotic patients (n=31) than in controls (n=10) (1.44 vs 1.00 x 10(-3) l/mmHg, p

  1. Increased arterial compliance in decompensated cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, Søren; Schifter, S

    1999-01-01

    BACKGROUND/AIMS: In patients with cirrhosis, the systemic circulation is hyperdynamic with low arterial blood pressure and reduced systemic vascular resistance. The present study was undertaken to estimate the compliance of the arterial tree in relation to severity of cirrhosis, circulating level...... of the vasodilator, calcitonin gene-related peptide (CGRP) and mean arterial blood pressure (MAP). METHODS: Arterial compliance (COMPart=deltaV/deltaP) was determined as the stroke volume relative to pulse pressure (i.e. systolic minus diastolic blood pressure) during a haemodynamic evaluation of portal hypertension...... of CGRP (r=0.34, pcompliance in cirrhosis is directly related to the severity of the disease and to the elevated level of circulating vasodilator peptide CGRP, and inversely related...

  2. Carotid artery disease

    Science.gov (United States)

    ... a blocked artery and places a tiny wire mesh (stent) in the artery to keep it open. ... Stony Brook, NY. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical ...

  3. Arterial bypass leg - slideshow

    Science.gov (United States)

    ... medlineplus.gov/ency/presentations/100155.htm Arterial bypass leg - series—Normal anatomy To use the sharing features ... Overview The arteries which supply blood to the leg originate from the aorta and iliac vessels. Review ...

  4. Hepatic artery aneurysms (HAAs)

    International Nuclear Information System (INIS)

    Nosratini, H.

    2004-01-01

    The hepatic artery aneurysms are rare, especially in interahepatic branches, The frequency consists of 75-80% extrahepatic and 20-25% intrahepatic. Catheterization is achieved usually from common femoral artery, other methods implemented in the case of unsuccessful catheterization from femoral artery, are translumbar and brachial catheterization. The study consist of 565 patients that were referred to the angiography ward, During seven years of assessment, five cases of hepatic artery aneurysm were found; this is a rare condition reported in the English literature. In the literature as well as in this case report the hepatic artery aneurysms are rare. In reported series the extrahepatic artery aneurysms are found more often than in the intrahepatic artery aneurysm but in this case report intrahepatic artery aneurysms are more than extrahepatic one. (author)

  5. Characteristics of arterial hypertension in obesity

    OpenAIRE

    Ivković-Lazar Tatjana A.

    2004-01-01

    Introduction Arterial hypertension is the most frequent cardiovascular disease in obese persons, progressing with time to left ventricular hypertension, often associated with dilatation, diastolic disorders, hearth rhythm disturbance, and generalized atherosclerosis. Etiology The origin of this disease is related to hemodynamic disturbances (increased blood volume, minute volume, mainly due to increased stroke volume) accompanied with changes of peripheral resistance, which increases in a lat...

  6. Vascular reactivity of mesenteric arteries and veins to endothelin-1 in a murine model of high blood pressure.

    Science.gov (United States)

    Pérez-Rivera, Alex A; Fink, Gregory D; Galligan, James J

    2005-06-01

    We characterized vascular reactivity to endothelin-1 (ET-1) in mesenteric vessels from DOCA-salt hypertensive and SHAM control mice and assessed the effect that endothelial-derived vasodilators have on ET-1-induced vasoconstriction. Changes in the diameter of unpressurized small mesenteric arteries and veins (100- to 300-microm outside diameter) were measured in vitro using computer-assisted video microscopy. Veins were more sensitive than arteries to the contractile effects of ET-1. There was a decrease in arterial maximal responses (E(max)) compared to veins, this effect was larger in DOCA-salt arteries. The selective ET(B) receptor agonist, sarafotoxin 6c (S6c), contracted DOCA-salt and SHAM veins but did not contract arteries. The ET(B) receptor antagonist, BQ-788 (100 nM), but not the ET(A) receptor antagonist, BQ-610 (100 nM), blocked S6c responses. BQ-610 partially inhibited responses to ET-1 in mesenteric veins from DOCA-salt and SHAM mice while BQ-788 did not affect responses to ET-1. Co-administration of both antagonists inhibited responses to ET-1 to a greater extent than BQ-610 alone suggesting a possible functional interaction between ET(A) and ET(B) receptors. Responses to ET-1 in mesenteric arteries were completely inhibited by BQ-610 while BQ-788 did not affect arterial responses. Nitric oxide synthase inhibition potentiated ET-1 responses in veins from SHAM but not DOCA-salt mice. There was a prominent role for ET-mediated nitric oxide release in DOCA-salt but not SHAM arteries. In summary, these studies showed a differential regulation of ET-1 contractile mechanisms between murine mesenteric arteries and veins.

  7. Measuring the Contractile Response of Isolated Tissue Using an Image Sensor

    Directory of Open Access Journals (Sweden)

    David Díaz-Martín

    2015-04-01

    Full Text Available Isometric or isotonic transducers have traditionally been used to study the contractile/relaxation effects of drugs on isolated tissues. However, these mechanical sensors are expensive and delicate, and they are associated with certain disadvantages when performing experiments in the laboratory. In this paper, a method that uses an image sensor to measure the contractile effect of drugs on blood vessel rings and other luminal organs is presented. The new method is based on an image-processing algorithm, and it provides a fast, easy and non-expensive way to analyze the effects of such drugs. In our tests, we have obtained dose-response curves from rat aorta rings that are equivalent to those achieved with classical mechanic sensors.

  8. Effect of a crude sulfated polysaccharide from Halymenia floresia (Rhodophyta on gastrointestinal smooth muscle contractility

    Directory of Open Access Journals (Sweden)

    José Ronaldo Vasconcelos Graça

    2011-10-01

    Full Text Available The aim of this work was to study the effect of Halymenia floresia (Hf on duodenum contractility, and on experimental protocols of gastric compliance (GC in rats. Fraction Hf2s exhibited a concentration-dependent myocontractile effect (EC50 12.48 µg/ml, and an inhibitory effect after consecutive washing. The contractile response promoted by Hf2s in the duodenum strips was completely inhibited by verapamil, and the effects were prevented in the presence of Ca2+-free medium. The pretreatment with atropine prevented the Hf2s myocontractile effect. Hf2s was also capable to decrease the GC (from 3.8±0.06 to 3.4±0.13 ml, P<0.05, which did not return to basal levels after more 50 min of observation. These results indicated that the algal polysaccharide possessed in vitro and in vivo gastrointestinal effects.

  9. Pharmacology of Casimiroa edulis; III. Relaxant and contractile effects in rat aortic rings.

    Science.gov (United States)

    Magos, G A; Vidrio, H; Enríquez, R

    1995-06-23

    The relaxant and contractile effects of an aqueous extract of the seeds of the hypotensive plant Casimiroa edulis were investigated in rat aortic rings. The extract inhibited contractions elicited by noradrenaline, serotonin and prostaglandin F2 alpha, but did not affect responses to KCl. Inhibition did not require the presence of intact vascular endothelium and was not affected by histamine antagonists. In this preparation, the extract also elicited concentration-related contractions which were more marked in the absence of endothelium, were not blocked by histamine antagonists, and were completely suppressed by alpha-adrenergic blockade. It was concluded that the relaxant effect of the extract is not exerted through release of an endothelial relaxing factor nor through blockade of calcium channels or of specific smooth muscle receptors, and does not involve histaminergic mechanisms. The contractile effect is modulated by vascular endothelium and is alpha-adrenergic in nature.

  10. BK channel activation by NS11021 decreases excitability and contractility of urinary bladder smooth muscle

    DEFF Research Database (Denmark)

    Layne, Jeffrey J; Nausch, Bernhard; Olesen, Søren-Peter

    2009-01-01

    reduction was blocked by pretreatment with the BK channel blocker iberiotoxin. NS11021 (3 microM) had no effect on contractions evoked by nerve stimulation. These findings indicate that activating BK channels reduces the force of UBSM spontaneous phasic contractions, principally through decreasing......Large-conductance Ca(2+)-activated potassium (BK) channels play an important role in regulating the function and activity of urinary bladder smooth muscle (UBSM), and the loss of BK channel function has been shown to increase UBSM excitability and contractility. However, it is not known whether...... activation of BK channels has the converse effect of reducing UBSM excitability and contractility. Here, we have sought to investigate this possibility by using the novel BK channel opener NS11021. NS11021 (3 microM) caused an approximately threefold increase in both single BK channel open probability (P...

  11. Effects of ageing on single muscle fibre contractile function following short-term immobilisation

    DEFF Research Database (Denmark)

    Hvid, Lars G; Ortenblad, Niels; Aagaard, Per

    2011-01-01

    Very little attention has been given to the combined effects of healthy ageing and short-term disuse on the contractile function of human single muscle fibres. Therefore, the present study investigated the effects of 2 weeks of lower limb cast immobilisation (i.e. disuse) on selected contractile.......05), respectively. In conclusion, 2 weeks of lower limb immobilisation caused greater impairments in single muscle fibre force and specific force in MHC IIa than MHC I fibres independently of age. In contrast, immobilisation-induced changes in Ca(2+) sensitivity that were dependent on age and MHC isoform....... properties of single muscle fibres (n = 378) from vastus lateralis of nine young (24 ± 1 years) and eight old (67 ± 2 years) healthy men with comparable levels of physical activity. Prior to immobilisation, MHC IIa fibres produced higher maximum Ca(2+)-activated force (approx. 32%) and specific force (approx...

  12. Effect of changes in contractility on the index of myocardial performance in the dysfunctional left ventricle

    Directory of Open Access Journals (Sweden)

    Lavine Steven J

    2006-11-01

    Full Text Available Abstract Background The index of myocardial performance has prognostic power in patients with cardiomyopathy and following myocardial infarction. As the index of myocardial performance has been shown to be preload and afterload dependent, the effect of altering contractility on IMP and its components with left ventricular dysfunction has been incompletely delineated. Methods Chronic left ventricular dysfunction was induced in 10 canines using coronary microsphere embolization. Each dog was instrumented and imaged with 2D echo and Doppler. At the same atrially paced rate, contractility was increased with a dobutamine infusion and then following 4 weeks of oral digoxin. Results With chronic left ventricular dysfunction, a reduced left ventricular ejection fraction (42 ± 3%, p Conclusion Increased inotropy with digoxin and dobutamine reduced the index of myocardial performance in dogs with left ventricular dysfunction. Shortened isovolumic contraction time, increased diastolic filling period, and reduced left ventricular end diastolic pressure with digoxin may provide insight into its efficacy in heart failure.

  13. A computerized experimental set-up for in vitro evaluation of smooth muscle contractility.

    Science.gov (United States)

    Das, J; Vereecken, R L; Schellemans, D

    1986-12-01

    A fully automated system is designed and developed for the investigation of in vitro contractility of muscle tissue in response to dose-dependent pharmacologic and/or electrical stimulation. The heart of the set-up is a personal technical computer. It drives the experiment by selecting and changing drug concentrations, by applying electrical stimulation, by sampling the tissue's contractile response and by real-time calculation of results. Parameters of interest are derived and updated for further selection and statistical manipulation. Alpha-numerical or graphical hardcopies may be drawn at any time. Investigator's intervention is limited to preparing perfusing solutions, mounting the muscle tissue strips, deciding test condition parameters, supervising the experimental progress and leading statistical calculations.

  14. Numerical investigation of perforated polymer microcantilever sensor for contractile behavior of cardiomyocytes

    Science.gov (United States)

    Khoa Nguyen, Trieu; Lee, Dong-Weon; Lee, Bong-Kee

    2017-06-01

    In this study, a numerical investigation of microcantilever sensors for detecting the contractile behavior of cardiomyocytes (CMs) was performed. Recently, a novel surface-patterned perforated SU-8 microcantilever sensor has been developed for the preliminary screening of cardiac toxicity. From the contractile motion of the CMs cultured on the microcantilever surface, a macroscopic bending of the microcantilever was obtained, which is considered to reflect a physiological change. As a continuation of the previous research, a novel numerical method based on a surface traction model was proposed and verified to further understand the bending behavior of the microcantilevers. Effects of various factors, including surface traction magnitude, focal area of CMs, and stiffness of microcantilever, on the bending displacement were investigated. From static and transient analyses, the focal area was found to be the most crucial factor. In addition, the current result can provide a design guideline for various micromechanical devices based on the same principle.

  15. Simultaneous measurement of arterial and left ventricular pressure in conscious freely moving rats by telemetry.

    Science.gov (United States)

    Segreti, Jason A; Polakowski, James S; Blomme, Eric A; King, Andrew J

    2016-01-01

    Comprehensive cardiovascular assessment in conscious rodents by utilizing telemetry has been limited by the restriction of current devices to one pressure channel. The purpose of this study was to test and validate a dual pressure transmitter that allows the simultaneous measurement of arterial pressure (AP) and left ventricular pressure (LVP) in conscious freely moving rats. Six rats were surgically implanted with dual pressure transmitters. Baseline hemodynamics and circadian rhythm were observed to return within 7days. AP, heart rate (HR), LVP and indices of left ventricular contractility were stable and demonstrated a prominent circadian rhythm over a two-week period of uninterrupted recordings. Administration of the vasodilator nifedipine produced the anticipated dose-dependent decrease in AP which was accompanied by a baroreflex mediated increase in HR and cardiac contractility. The negative inotrope verapamil produced the expected dose-dependent decreases in AP and cardiac contractility. Finally, a terminal validation of the dual pressure transmitter was performed under anesthesia by measuring AP and LVP simultaneously via telemetry and from a fluid filled arterial catheter and an intraventricular Millar catheter, respectively. A range of pressures and cardiac contractility were studied by administering sequential intravenous infusions of the positive inotrope dobutamine followed by verapamil. Linear regression analysis revealed a high level of agreement between pressures measured by the dual pressure transmitter and the exteriorized catheters. Histopathologic analysis of the heart revealed mild peri-catheter fibrosis. In conclusion, the simultaneous measurement of AP and LVP offers the potential for more detailed cardiovascular assessment in conscious rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Ultrasound diagnosis of pulmonary sling with proximal stenosis of left pulmonary artery and patent arterial duct

    Directory of Open Access Journals (Sweden)

    Wojciech Mądry

    2013-03-01

    Full Text Available Authors discuss methods of echocardiographic diagnosis of the pulmonary sling with stenosis and hypoplasia of the left pulmonary artery and patent arterial duct with massive left‑to‑right shunt, based on a case of the newborn with resistant to treatment heart failure, with initial diagnosis of patent ductus arteriosus, referred to surgical treatment. The optimal echocardiographic views permitting establish diagnosis of the pulmonary sling were suggested. The special attention was paid to high parasternal and suprasternal views visualizing vessels of the upper mediastinum as well as characteristic differences between the normal and pathologic picture. The typical features of the echocardiogram suggesting pulmonary sling, like the lack of the left pulmonary artery in its expected position, and the abnormal branching pattern of the right pulmonary artery were indicated. The greatest diagnostic difficulties in visualization of the abnormal route of the left pulmonary artery were related to the presence of air‑containing tissues, like lungs and central airways between the ultrasound probe and area of interest. The other was the masking influence of the large patent arterial duct, that may mimic the left pulmonary artery arising from the pulmonary trunk. The other entities requiring differentiation with sling, like aplasia of the left lung, the direct or indirect aortic origin of the left pulmonary artery, were discussed. The role of other visualization technics, like computed 3D tomography, and magnetic nuclear resonance, as well as direct visualization of central airways with bronchoscopy in establishing precise diagnosis were stressed.

  17. Slow force response and auto-regulation of contractility in heterogeneous myocardium.

    Science.gov (United States)

    Markhasin, Vladimir S; Balakin, Alexander A; Katsnelson, Leonid B; Konovalov, Pavel; Lookin, Oleg N; Protsenko, Yuri; Solovyova, Olga

    2012-01-01

    Classically, the slow force response (SFR) of myocardium refers to slowly developing changes in cardiac muscle contractility induced by external mechanical stimuli, e.g. sustained stretch. We present evidence for an intra-myocardial SFR (SFR(IM)), caused by the internal mechanical interactions of muscle segments in heterogeneous myocardium. Here we study isometric contractions of a pair of end-to-end connected functionally heterogeneous cardiac muscles (an in-series muscle duplex). Duplex elements can be either biological muscles (BM), virtual muscles (VM), or a hybrid combination of BM and VM. The VM implements an Ekaterinburg-Oxford mathematical model accounting for the ionic and myofilament mechanisms of excitation-contraction coupling in cardiomyocytes. SFR(IM) is expressed in gradual changes in the overall duplex force and in the individual contractility of each muscle, induced by cyclic auxotonic deformations of coupled muscles. The muscle that undergoes predominant cyclic shortening shows force enhancement upon return to its isometric state in isolation, whereas average cyclic lengthening may decrease the individual muscle contractility. The mechanical responses are accompanied with slow and opposite changes in the shape and duration of both the action potential and Ca²⁺ transient in the cardiomyocytes of interacting muscles. Using the mathematical model we found that the contractility changes in interacting muscles follow the alterations in the sarcoplasmic reticulum loading in cardiomyocytes which result from the length-dependent Ca²⁺ activation of myofilaments and intracellular mechano-electrical feedback. The SFR(IM) phenomena unravel an important mechanism of cardiac functional auto-regulation applicable to the heart in norm and pathology, especially to hearts with severe electrical and/or mechanical dyssynchrony. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity and carbonyl formation. Kaplan-Meier curve was constructed for survival following LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice following LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O2−, and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury following LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by antioxidant NAC and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. PMID:22902401

  19. Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy.

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F; Roe, Nathan D; Hu, Nan; Gao, Feng; Ren, Jun

    2012-09-15

    Lipopolysaccharide (LPS) from gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complications in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis, and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity, and carbonyl formation. A Kaplan-Meier curve was constructed for survival after LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice after LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O(2)(-), and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury after LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by the antioxidant N-acetylcysteine and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    OpenAIRE

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged ...

  1. Cardiac myofibrillar contractile properties during the progression from hypertension to decompensated heart failure.

    Science.gov (United States)

    Hanft, Laurin M; Emter, Craig A; McDonald, Kerry S

    2017-07-01

    Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, Ca 2+ handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of the present study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt heart failure, we predicted marked depression in these contractile properties. We assessed contractile properties in skinned cardiac myocyte preparations from left ventricles of Wistar-Kyoto control rats and spontaneous hypertensive heart failure (SHHF) rats at ~3, ~12, and >20 mo of age to evaluate the time course of myofilament properties associated with normal aging processes compared with myofilaments from rats with a predisposition to heart failure. In control rats, the myofilament contractile properties were virtually unchanged throughout the aging process. Conversely, in SHHF rats, the rate of force development, loaded shortening velocity, and power all increased at ~12 mo and then significantly fell at the >20-mo time point, which coincided with a decrease in left ventricular fractional shortening. Furthermore, these changes occurred independent of changes in β-myosin heavy chain but were associated with depressed phosphorylation of myofibrillar proteins, and the fall in loaded shortening and peak power output corresponded with the onset of clinical signs of heart failure. NEW & NOTEWORTHY This novel study systematically examined the power-generating capacity of cardiac myofilaments during the progression from hypertension to heart disease. Previously

  2. Myosin phosphorylation improves contractile economy of mouse fast skeletal muscle during staircase potentiation.

    Science.gov (United States)

    Bunda, Jordan; Gittings, William; Vandenboom, Rene

    2018-01-30

    Phosphorylation of the myosin regulatory light chain (RLC) by skeletal myosin light chain kinase (skMLCK) potentiates rodent fast twitch muscle but is an ATP-requiring process. Our objective was to investigate the effect of skMLCK-catalyzed RLC phosphorylation on the energetic cost of contraction and the contractile economy (ratio of mechanical output to metabolic input) of mouse fast twitch muscle in vitro (25°C). To this end, extensor digitorum longus (EDL) muscles from wild-type (WT) and from skMLCK-devoid (skMLCK -/- ) mice were subjected to repetitive low-frequency stimulation (10 Hz for 15 s) to produce staircase potentiation of isometric twitch force, after which muscles were quick frozen for determination of high-energy phosphate consumption (HEPC). During stimulation, WT muscles displayed significant potentiation of isometric twitch force while skMLCK -/- muscles did not (i.e. 23% versus 5% change, respectively). Consistent with this, RLC phosphorylation was increased ∼3.5-fold from the unstimulated control value in WT but not in skMLCK -/- muscles. Despite these differences, the HEPC of WT muscles was not greater than that of skMLCK -/- muscles. As a result of the increased contractile output relative to HEPC, the calculated contractile economy of WT muscles was greater than that of skMLCK -/- muscles. Thus, our results suggest that skMLCK-catalyzed phosphorylation of the myosin RLC increases the contractile economy of WT mouse EDL muscle compared with skMLCK -/- muscles without RLC phosphorylation. © 2018. Published by The Company of Biologists Ltd.

  3. Robust gap repair in the contractile ring ensures timely completion of cytokinesis.

    OpenAIRE

    Silva, AM; Osório, DS; Pereira, AJ; Maiato, H; Pinto, IM; Rubinstein, B; Gassmann, R; Telley, IA; Carvalho, AX

    2016-01-01

    Cytokinesis in animal cells requires the constriction of an actomyosin contractile ring, whose architecture and mechanism remain poorly understood. We use laser microsurgery to explore the biophysical properties of constricting rings in Caenorhabditis elegans embryos. Laser cutting causes rings to snap open. However, instead of disintegrating, ring topology recovers and constriction proceeds. In response to severing, a finite gap forms and is repaired by recruitment of new material in an acti...

  4. The Effects of Histamine H3 Receptors on Contractile Responses on Rat Gastric Fundus

    OpenAIRE

    Aşkın Hekimoğlu; Ramazan Çiçek

    2006-01-01

    The aim of this study is to determine the effects of histamine receptors on the gastrointestinal system smooth muscle contractions and the role of histamine H3 receptors on these effects. İsolated rat gastric fundus preparations were hanged on isolated organ bath and histamine receptor agonist and anthagonists were added to the bath solution and the electrical field stimulation-induced contractile responses were evaluated. In our study groups after blocking one of the histamine receptor...

  5. History of uterine artery occlusion and subsequent pregnancy.

    Science.gov (United States)

    Burbank, Fred

    2009-06-01

    During mature placenta formation, select fetal trophoblasts invade maternal decidual arterioles and junctional zone arteries and change them into low-resistance uteroplacental arteries. Consequently, physicians performing vascular procedures that occlude the uterine arteries should understand their effects on miscarriage rates, the various toxemias of pregnancy, gross and microscopic placental anatomy, and invasive placentation. Thus, the objective of this article is to review the effects of vascular occlusion on pregnancy. In the long run, placental abnormalities may be the canary in the mine shaft to globally judge the effect of uterine artery embolization on pregnancy.

  6. Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion.

    Science.gov (United States)

    Ronan, William; Deshpande, Vikram S; McMeeking, Robert M; McGarry, J Patrick

    2014-04-01

    Numerous experimental studies have established that cells can sense the stiffness of underlying substrates and have quantified the effect of substrate stiffness on stress fibre formation, focal adhesion area, cell traction, and cell shape. In order to capture such behaviour, the current study couples a mixed mode thermodynamic and mechanical framework that predicts focal adhesion formation and growth with a material model that predicts stress fibre formation, contractility, and dissociation in a fully 3D implementation. Simulations reveal that SF contractility plays a critical role in the substrate-dependent response of cells. Compliant substrates do not provide sufficient tension for stress fibre persistence, causing dissociation of stress fibres and lower focal adhesion formation. In contrast, cells on stiffer substrates are predicted to contain large amounts of dominant stress fibres. Different levels of cellular contractility representative of different cell phenotypes are found to alter the range of substrate stiffness that cause the most significant changes in stress fibre and focal adhesion formation. Furthermore, stress fibre and focal adhesion formation evolve as a cell spreads on a substrate and leading to the formation of bands of fibres leading from the cell periphery over the nucleus. Inhibiting the formation of FAs during cell spreading is found to limit stress fibre formation. The predictions of this mutually dependent material-interface framework are strongly supported by experimental observations of cells adhered to elastic substrates and offer insight into the inter-dependent biomechanical processes regulating stress fibre and focal adhesion formation.

  7. Changes of contractile responses due to simulated weightlessness in rat soleus muscle

    Science.gov (United States)

    Elkhammari, A.; Noireaud, J.; Léoty, C.

    1994-08-01

    Some contractile and electrophysiological properties of muscle fibers isolated from the slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles of rats were compared with those measured in SOL muscles from suspended rats. In suspendede SOL (21 days of tail-suspension) membrane potential (Em), intracellular sodium activity (aiNa) and the slope of the relationship between Em and log [K]o were typical of fast-twitch muscles. The relation between the maximal amplitude of K-contractures vs Em was steeper for control SOL than for EDL and suspended SOL muscles. After suspension, in SOL muscles the contractile threshold and the inactivation curves for K-contractures were shifted to more positive Em. Repriming of K-contractures was unaffected by suspencion. The exposure of isolated fibers to perchlorate (ClO4-)-containing (6-40 mM) solutions resulted ina similar concentration-dependent shift to more negative Em of activation curves for EDL and suspended SOL muscles. On exposure to a Na-free TEA solution, SOL from control and suspended rats, in contrast to EDL muscles, generated slow contractile responses. Suspended SOL showed a reduced sensitivity to the contracture-producing effect of caffeine compared to control muscles. These results suggested that the modification observed due to suspension could be encounted by changes in the characteristics of muscle fibers from slow to fast-twitch type.

  8. Combination Therapy Comprising a Static Magnetic Field with Contractility Improves Skin Wounds.

    Science.gov (United States)

    Song, Byeong-Wook; Hong, Hyunki; Jung, Yu Jin; Lee, Ju Hyung; Kim, Bong-Soo; Lee, Hoon-Bum

    2018-03-21

    Cutaneous wounds can present significant clinical problems because of abnormal healing after deep dermal damage. Despite technical advances in wound care, there are still unmet needs that result from inefficient treatment. In this study, we aimed to improve skin wound healing using a contractibility band with static magnetic field (SMF), termed a Magnetic band (Mb). To examine the effect of the Mb on wound healing, full-thickness 15 mm × 35 mm excision wounds were surgically created on the dorsum of rats. An elastic and contractile band (non-treatment), or one neodymium magnet (Nd-1) or two magnets with an elastic and contractile band (Nd-2) were topically applied to the wound daily and the wound size was measured from day 1 to 7 after surgery. Nd-2 showed a significant (95%) reduction in the wound size at day 3. Histological analysis showed that pro-inflammatory cytokine levels were diminished by Nd-2, and granulation tissue and microvessels were increased compared with those in the sham group. During Mb-induced wound healing, apoptosis was significantly reduced and matrix remodeling-related factors were initially regulated. The results suggest that combination therapy comprising an SMF and an elastic and contractile band could be a promising tool to heal cutaneous wounds rapidly.

  9. Impact of tamsulosin and nifedipine on contractility of pregnant rat ureters in vitro.

    Science.gov (United States)

    Haddad, Lisette; Corriveau, Stéphanie; Rousseau, Eric; Blouin, Simon; Pasquier, Jean-Charles; Ponsot, Yves; Roy-Lacroix, Marie-Ève

    2018-01-01

    To evaluate the in vitro effect of tamsulosin and nifedipine on the contractility of pregnant rat ureters and to perform quantitative analysis of the pharmacological effects. Medical expulsive therapy (MET) is commonly used to treat urolithiasis. However, this treatment is seldom used in pregnant women since no studies support this practice. This was an in vitro study on animal tissue derived from pregnant Sprague-Dawley rats. A total of 124 ureteral segments were mounted in an organ bath system and contractile response to methacholine (MCh) was assessed. Tamsulosin or nifedipine were added at cumulative concentrations (0.001-1 μM). The area under the curve (AUC) from isometric tension measurements was calculated. The effect of pharmacological agents and the respective controls were assessed by calculating the AUC for each 5-min interval. Statistical analyses were performed using the Mann-Whitney-Wilcoxon nonparametric test. Both drugs displayed statistically significant inhibitory activity at concentrations of 0.1 and 1 μM for tamsulosin and 1 μM for nifedipine when calculated as the AUC as compared to DMSO controls. Tamsulosin and nifedipine directly inhibit MCh-induced contractility of pregnant rat ureters. Further work is needed to determine the clinical efficacy of these medications for MET in pregnancy.

  10. Improvement of diaphragm and limb muscle isotonic contractile performance by K+ channel blockade

    Directory of Open Access Journals (Sweden)

    Pollarine Jennifer

    2010-01-01

    Full Text Available Abstract The K+ channel blocking aminopyridines greatly improve skeletal muscle isometric contractile performance during low to intermediate stimulation frequencies, making them potentially useful as inotropic agents for functional neuromuscular stimulation applications. Most restorative applications involve muscle shortening; however, previous studies on the effects of aminopyridines have involved muscle being held at constant length. Isotonic contractions differ substantially from isometric contractions at a cellular level with regards to factors such as cross-bridge formation and energetic requirements. The present study tested effects of 3,4-diaminopyridine (DAP on isotonic contractile performance of diaphragm, extensor digitorum longus (EDL and soleus muscles from rats. During contractions elicited during 20 Hz stimulation, DAP improved work over a range of loads for all three muscles. In contrast, peak power was augmented for the diaphragm and EDL but not the soleus. Maintenance of increased work and peak power was tested during repetitive fatigue-inducing stimulation using a single load of 40% and a stimulation frequency of 20 Hz. Work and peak power of both diaphragm and EDL were augmented by DAP for considerable periods of time, whereas that of soleus muscle was not affected significantly. These results demonstrate that DAP greatly improves both work and peak power of the diaphragm and EDL muscle during isotonic contractions, which combined with previous data on isometric contractions indicates that this agent is suitable for enhancing muscle performance during a range of contractile modalities.

  11. Acute pergolide exposure stiffens engineered valve interstitial cell tissues and reduces contractility in vitro.

    Science.gov (United States)

    Capulli, Andrew K; MacQueen, Luke A; O'Connor, Blakely B; Dauth, Stephanie; Parker, Kevin Kit

    2016-01-01

    Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the US market in 1997 and pergolide, a Parkinson's disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease. Failure to identify these risks prior to market and continued use of similar drugs reaffirm the need to improve preclinical evaluation of drug-induced VHD. Here, we present two complimentary assays to measure stiffness and contractile stresses generated by engineered valvular tissues in vitro. As a case study, we measured the effects of acute (24 h) pergolide exposure to engineered porcine aortic valve interstitial cell (AVIC) tissues. Pergolide exposure led to increased tissue stiffness, but it decreased both basal and active contractile tone stresses generated by AVIC tissues. Pergolide exposure also disrupted AVIC tissue organization (i.e., tissue anisotropy), suggesting that the mechanical properties and contractile functionality of these tissues are governed by their ability to maintain their structure. We expect further use of these assays to identify off-target drug effects that alter the phenotypic balance of AVICs, disrupt their ability to maintain mechanical homeostasis, and lead to VHD. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Kaurane and pimarane-type diterpenes from the Viguiera species inhibit vascular smooth muscle contractility.

    Science.gov (United States)

    Ambrosio, Sergio R; Tirapelli, Carlos R; da Costa, Fernando B; de Oliveira, Ana M

    2006-08-01

    The research, development and use of natural products as therapeutic agents, especially those derived from plants, have been increasing in recent years. Despite the fact that plants provide a rich source of novel biologically active compounds, only a small percentage have been phytochemically investigated and studied for their medical potential. Viguiera is a genus that belongs to the family Asteraceae and to the sunflower tribe Heliantheae, which is widespread mostly in Mexico and in other areas of the Andes and upland areas of Brazil. A review on the secondary metabolites pointed out that sesquiterpene lactones and diterpenes, of the kaurane and pimarane-type, are the main compounds produced by these plants. Some reports have shown that kaurane- and pimarane-type diterpenes exert several biological activities such as anti-inflammatory action, antimicrobial and antispasmodic activities. Kaurenoic and pimaradienoic acids, which are the main secondary metabolites isolated by our research group from the roots of Viguiera robusta and V. arenaria, respectively, have been evaluated on vascular smooth muscle contractility. We showed that these diterpenoids are able to inhibit the vascular contractility mainly by blocking extracellular Ca(2+) influx. Additionally, in this review we discuss the structure-activity relationship of the diterpenes regarding their inhibitory activity on vascular contractility.

  13. Impaired contractility and remodeling of the upper gastrointestinal tract in diabetes mellitus type-1.

    Science.gov (United States)

    Frokjaer, Jens Brondum; Andersen, Soren-Due; Ejskjaer, Niels; Funch-Jensen, Peter; Drewes, Asbjorn-Mohr; Gregersen, Hans

    2007-09-28

    To investigate that both the neuronal function of the contractile system and structural apparatus of the gastrointestinal tract are affected in patients with longstanding diabetes and auto mic neuropathy. The evoked esophageal and duodenal contractile activity to standardized bag distension was assessed using a specialized ultrasound-based probe. Twelve type-1 diabetic patients with autonomic neuropathy and severe gastrointestinal symptoms and 12 healthy controls were studied. The geometry and biomechanical parameters (strain, tension/stress, and stiffness) were assessed. The diabetic patients had increased frequency of distension-induced contractions (6.0 +/- 0.6 vs 3.3 +/- 0.5, P 0.14). The impaired contractile activity with an imbalance in the distension-induced contractions likely reflects neuronal abnormalities due to autonomic neuropathy. However, structural changes and remodeling of the gastrointestinal tract are also evident and may add to the neuronal changes. This may contribute to the pathophysiology of diabetic gut dysfunction and impact on future management of diabetic patients with gastrointestinal symptoms.

  14. Acute Pergolide Exposure Stiffens Engineered Valve Interstitial Cell Tissues and Reduces Contractility In Vitro

    Science.gov (United States)

    Capulli, Andrew K.; MacQueen, Luke A.; O’Connor, Blakely B.; Dauth, Stephanie; Parker, Kevin Kit

    2016-01-01

    Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the U.S. market in 1997 and pergolide, a Parkinson’s disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease. Failure to identify these risks prior to market, and continued use of similar drugs, reaffirms the need to improve preclinical evaluation of drug-induced VHD. Here, we present two complimentary assays to measure stiffness and contractile stresses generated by engineered valvular tissues in vitro. As a case study, we measured the effects of acute (24 hr) pergolide exposure to engineered porcine aortic valve interstitial cell (AVIC) tissues. Pergolide exposure led to increased tissue stiffness but it decreased both basal and active contractile tone stresses generated by AVIC tissues. Pergolide exposure also disrupted AVIC tissue organization (i.e., tissue anisotropy), suggesting that the mechanical properties and contractile functionality of these tissues are governed by their ability to maintain their structure. We expect further use of these assays to identify off-target drug effects that alter the phenotypic balance of AVICs, disrupt their ability to maintain mechanical homeostasis, and lead to VHD. PMID:27174867

  15. Robust gap repair in the contractile ring ensures timely completion of cytokinesis.

    Science.gov (United States)

    Silva, Ana M; Osório, Daniel S; Pereira, Antonio J; Maiato, Helder; Pinto, Inês Mendes; Rubinstein, Boris; Gassmann, Reto; Telley, Ivo Andreas; Carvalho, Ana Xavier

    2016-12-19

    Cytokinesis in animal cells requires the constriction of an actomyosin contractile ring, whose architecture and mechanism remain poorly understood. We use laser microsurgery to explore the biophysical properties of constricting rings in Caenorhabditis elegans embryos. Laser cutting causes rings to snap open. However, instead of disintegrating, ring topology recovers and constriction proceeds. In response to severing, a finite gap forms and is repaired by recruitment of new material in an actin polymerization-dependent manner. An open ring is able to constrict, and rings repair from successive cuts. After gap repair, an increase in constriction velocity allows cytokinesis to complete at the same time as controls. Our analysis demonstrates that tension in the ring increases while net cortical tension at the site of ingression decreases throughout constriction and suggests that cytokinesis is accomplished by contractile modules that assemble and contract autonomously, enabling local repair of the actomyosin network. Consequently, cytokinesis is a highly robust process impervious to discontinuities in contractile ring structure. © 2016 Silva et al.

  16. Morphometric Parameters, Contractility and Architecture of the Left Ventricle Myocardium in Pigs

    Directory of Open Access Journals (Sweden)

    Mikhail P. Roshchevsky, PhD, ScD

    2012-03-01

    Full Text Available This study aims to reveal the interrelations found within the architecture of the muscular fibers, the morphometric parameters and contractility of the left ventricular myocardium in the Landrace breed of conventional pigs. The left ventricular morphometric parameters were investigated at three levels (basal, middle, apical utilizing echocardiography, myocardial contractility was estimated by the ejection fraction, fractional shortening and fractional thickening. The fiber architecture of the working myocardium was studied following the method of the layer-by-layer splitting of muscular fibers. The fibers ofthe superficial and deep layers of the left ventricle showed an oblique orientation, while the muscular fibers of the middle layer were distinguishable as high-lying and low-lying fibers. During the cardiac cycle, the greatest reduction in the transverse dimension and the greatest thickening of the walls were observed in the middle level when compared with the basal and apical levels, that is related with more thick layer of muscular circumferential fibers in the middle section of the ventricle and large papillary muscles. A low contractile ability of the left ventricle myocardium was revealed in pigs.

  17. Morphology, ultrastructure and contractile properties of muscles responsible for superior tentacle movements of the snail.

    Science.gov (United States)

    Krajcs, Nóra; Márk, L; Elekes, K; Kiss, T

    2012-01-01

    Bending, twitching and quivering are different types of tentacle movements observed during olfactory orientation of the snail. Three recently discovered special muscles, spanning along the length of superior tentacles from the tip to the base, seem to be responsible for the execution of these movements. In this study we have investigated the ultrastructure, contractile properties and protein composition of these muscles. Our ultrastructural studies show that smooth muscle fibers are loosely embedded in a collagen matrix and they are coupled with long sarcolemma protrusions. The muscle fibers apparently lack organized SR and transverse tubular system. Instead subsarcolemmal vesicles and mitochondria have been shown to be possible Ca2+ pools for contraction. It was shown that external Ca2+ is required for contraction elicited by high (40 mM) K+ or 10-4 M ACh. Caffeine (5 mM) induced contraction in Ca2+-free solution suggesting the presence of a substantial intracellular Ca2+ pool. High-resolution electrophoretic analysis of columellar and tentacular muscles did not reveal differences in major contractile proteins, such as actin, myosin and paramyosin. Differences were observed however in several bands representing presumably regulatory enzymes. It is concluded that, the ultrastructural, biochemical and contractile properties of the string muscles support their special physiological function.

  18. Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.

    Science.gov (United States)

    Spaulding, Kimberly; Takaba, Kiyoaki; Collins, Alexander; Faraji, Farshid; Wang, Guanying; Aguayo, Esteban; Ge, Liang; Saloner, David; Wallace, Arthur W; Baker, Anthony J; Lovett, David H; Ratcliffe, Mark B

    2018-01-01

    Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; pborder zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity.

  19. Adaptive responses of mouse skeletal muscle to contractile activity: The effect of age.

    Science.gov (United States)

    Vasilaki, A; McArdle, F; Iwanejko, L M; McArdle, A

    2006-11-01

    This study has characterised the time course of two major transcriptional adaptive responses to exercise (changes in antioxidant defence enzyme activity and heat shock protein (HSP) content) in muscles of adult and old male mice following isometric contractions and has examined the mechanisms involved in the age-related reduction in transcription factor activation. Muscles of B6XSJL mice were subjected to isometric contractions and analysed for antioxidant defence enzyme activities, heat shock protein content and transcription factor DNA binding activity. Data demonstrated a significant increase in superoxide dismutase (SOD) and catalase activity and HSP content of muscles of adult mice following contractile activity which was associated with increased activation of the transcription factors, nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and heat shock factor (HSF) following contractions. Significant increases in SOD and catalase activity and heat shock cognate (HSC70) content were seen in quiescent muscles of old mice. The increase in antioxidant defence enzyme activity following contractile activity seen in muscles of adult mice was not seen in muscles of old mice and this was associated with a failure to fully activate NF-kappaB and AP-1 following contractions. In contrast, although the production of HSPs was also reduced in muscles of old mice following contractile activity compared with muscles of adult mice following contractions, this was not due to a gross reduction in the DNA binding activity of HSF.

  20. Alteration of Na-K pump activity in supersensitive rat caudal artery following 6-hydroxydopamine (6-OHDA) treatment

    International Nuclear Information System (INIS)

    Wong, S.K.; Foley, D.H.

    1986-01-01

    Contractile response and the Na-K pump activity, measured as ouabain-sensitive 86 Rb-uptake, were determined in caudal artery strips of rats pretreated with 6-OHDA. At 6-7 days after 6-OHDA treatment, the potencies of norepinephrine and serotonin in causing contraction of rat caudal artery were significantly increased by 2.3 - and 1.7 - fold respectively. There was, however, no change in maximum contractile response to either agent. Treatment with 6-OHDA also reduced endogenous catecholamine content of the caudal artery to 7% of the control. Analysis of ouabain-inhibitable 86 Rb-uptake of rat caudal artery by the double-reciprocal plots showed that both the rate of 86 Rb-uptake and the affinity for rubidium were depressed after 6-OHDA treatment. The results indicate that 6-OHDA induced supersensitivity in the rat caudal artery is associated with a decrease in the Na-K pump activity. These data provide additional support to the concept that inhibition of the Na-K pump may result in partial depolarization of the cell membrane which leads to supersensitivity of smooth muscle to excitatory drugs

  1. Galectin-3 and fibulin-1 in systolic heart failure - relation to glucose metabolism and left ventricular contractile reserve

    OpenAIRE

    Holmager, Pernille; Egstrup, Michael; Gustafsson, Ida; Schou, Morten; Dahl, Jordi S.; Rasmussen, Lars Melholt; M?ller, Jacob E.; Tuxen, Christian; Faber, Jens; Kistorp, Caroline

    2017-01-01

    Background: Heart failure (HF) patients with diabetes (DM) have an adverse prognosis and reduced functional capacity, which could be associated with cardiac fibrosis, increased chamber stiffness and reduced left ventricular (LV) contractile reserve. Galectin-3 (Gal-3) and fibulin-1 are circulating biomarkers potentially reflecting cardiac fibrosis. We hypothesize that plasma levels of Gal-3 and fibulin-1 are elevated in HF patients with DM and are associated with reduced LV contractile reserv...

  2. Sildenafil dilates ophthalmic artery in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Akeel AMH Zwain

    2013-08-01

    Full Text Available Background: Conflicting reports exist on the effect of sildenafil on ophthalmic artery blood flow; many visual disturbances due to vascular insult were reported with the use of sildenafil in diabetic patients like nonarteritic ischemic optic neuropathy. Objectives: The present work aimed to investigate whether sildenafil modulates ophthalmic artery vasoreactivity in patients with type 2 diabetes mellitus. Literature reports on this aspect are lacking. Methods: A total of 35 male subjects were enrolled in this study, 18 with type 2 diabetes mellitus matched with 17 normal individuals. Ophthalmic artery was insonated through a transorbital window using colored Doppler equipment with transcranial Doppler facility. Ophthalmic artery reactivity was assessed using breath holding/hyperventilation test, before and after giving 50 mg oral sildenafil. Results: It was found that in both normal subjects and diabetic patients, sildenafil increased baseline control of mean flow velocity of ophthalmic artery significantly (p 0.05 after sildenafil, in normal and diabetic groups. There was a significant increase of resistive index of ophthalmic artery flow in diabetic patients compared with that of normal subject (p < 0.05. Sildenafil decreased resistive index of ophthalmic artery flow significantly only in diabetic patients (p < 0.05. Conclusion: Sildenafil increased MFVopa, but had no significant effect on vasoreactivity of ophthalmic artery; sildenafil decreased resistive index only in type 2 diabetic patients.

  3. Effects of hot shot (non cardioplegic blood based) on cardiac contractility and rhythm as parameters of myocardial protection in cabg surgery abstract objective

    International Nuclear Information System (INIS)

    Janjua, A.M.; Iqbal, M.A.; Rashid, A.

    2012-01-01

    To compare the effects of warm blood cardioplegia along with hot shot (non-cardioplegic blood based) at the end of ischemic time to warm blood cardioplegia without hot shot to assess resumption of effective electromechanical activity and need for internal electrical cardioversion as indicators of myocardial protection and preservation. Study Design: Randomized control trial. Place and Duration: The study was conducted at Armed Forces Institute of Cardiology (AFIC), Rawalpindi for a period of 10 months (March 2009 - Dec 2009). Patients and Methods: Total 100 patients of coronary artery disease having coronary artery bypass grafting (CABG) surgery were equally and randomly divided into two groups using random numbers table. Group A (n=50), consisted of warm blood cardioplegia with non cardioplegic blood based hot shot and group B (n=50), consisted of warm blood cardioplegia only. The adequacy of myocardial protection techniques was assessed by noting the time interval (in seconds) between declamping of the ascending aorta and patient regaining electromechanical activity. Additional parameters were rhythm, use of internal cardiac defibrillation, inotropes, IABP requirement and ECG evidenced peri-op MI. Results: Average age in group A was 56.98 +- 9.47 years and in Group B it was 59.1 9.35 years. In group A there were 48 (96%) males and group B there were 43 (86%) males with p-value of 0.081. Comparison of preoperative variables of both the groups revealed no difference in cross clamp time (p=0.52), CPB time (p = 0.68) and endarterectomy (p=0.55). The electromechanical activity (contractility of heart) returned within 7.53 +- 2.09 min in group A as compared to 9.81 +- 2.6 min in group B (p<0.001). Significantly high frequency was observed for defibrillation (p=0.025), inotropic support (p=0.045) and IABP insertion (p=0.041) in group B as compared to group A. Conclusion: In CABG surgery the additional use of hot shot (non cardioplegic blood based) during cardiopulmonary

  4. Novel method to study pericyte contractility and responses to ischaemia in vitro using electrical impedance.

    Science.gov (United States)

    Neuhaus, Ain A; Couch, Yvonne; Sutherland, Brad A; Buchan, Alastair M

    2017-06-01

    Pericytes are contractile vascular mural cells overlying capillary endothelium, and they have been implicated in a variety of functions including regulation of cerebral blood flow. Recent work has suggested that both in vivo and ex vivo, ischaemia causes pericytes to constrict and die, which has implications for microvascular reperfusion. Assessing pericyte contractility in tissue slices and in vivo is technically challenging, while in vitro techniques remain unreliable. Here, we used isolated cultures of human brain vascular pericytes to examine their contractile potential in vitro using the iCelligence electrical impedance system. Contraction was induced using the vasoactive peptide endothelin-1, and relaxation was demonstrated using adenosine and sodium nitroprusside. Endothelin-1 treatment also resulted in increased proliferation, which we were able to monitor in the same cell population from which we recorded contractile responses. Finally, the observation of pericyte contraction in stroke was reproduced using chemical ischaemia, which caused a profound and irreversible contraction clearly preceding cell death. These data demonstrate that isolated pericytes retain a contractile phenotype in vitro, and that it is possible to quantify this contraction using real-time electrical impedance recordings, providing a significant new platform for assessing the effects of vasoactive and vasculoprotective compounds on pericyte contractility.

  5. The Critical Role of Pulmonary Arterial Compliance in Pulmonary Hypertension

    Science.gov (United States)

    Prins, Kurt W.; Pritzker, Marc R.; Scandurra, John; Volmers, Karl; Weir, E. Kenneth

    2016-01-01

    The normal pulmonary circulation is a low-pressure, high-compliance system. Pulmonary arterial compliance decreases in the presence of pulmonary hypertension because of increased extracellular matrix/collagen deposition in the pulmonary arteries. Loss of pulmonary arterial compliance has been consistently shown to be a predictor of increased mortality in patients with pulmonary hypertension, even more so than pulmonary vascular resistance in some studies. Decreased pulmonary arterial compliance causes premature reflection of waves from the distal pulmonary vasculature, leading to increased pulsatile right ventricular afterload and eventually right ventricular failure. Evidence suggests that decreased pulmonary arterial compliance is a cause rather than a consequence of distal small vessel proliferative vasculopathy. Pulmonary arterial compliance decreases early in the disease process even when pulmonary artery pressure and pulmonary vascular resistance are normal, potentially enabling early diagnosis of pulmonary vascular disease, especially in high-risk populations. With the recognition of the prognostic importance of pulmonary arterial compliance, its impact on right ventricular function, and its contributory role in the development and progression of distal small-vessel proliferative vasculopathy, pulmonary arterial compliance is an attractive target for the treatment of pulmonary hypertension. PMID:26848601

  6. Heightened Pelvic Floor Muscle Tone and Altered Contractility in Women With Provoked Vestibulodynia.

    Science.gov (United States)

    Morin, Mélanie; Binik, Yitzchak M; Bourbonnais, Daniel; Khalifé, Samir; Ouellet, Stéphane; Bergeron, Sophie

    2017-04-01

    Pelvic floor muscle (PFM) dysfunctions are reported to be involved in provoked vestibulodynia (PVD). Although heightened PFM tone has been suggested, the relative contribution of active and passive components of tone remains misunderstood. Likewise, alterations in PFM contractility have been scarcely studied. To compare PFM tone, including the relative contribution of its active and passive components, and muscular contractility in women with PVD and asymptomatic controls. Fifty-six asymptomatic women and 56 women with PVD participated in the study. The PVD diagnosis was confirmed by a gynecologist based on a standardized examination. PFM function was evaluated using a dynamometric speculum combined with surface electromyography (EMG). PFM general tone was evaluated in static conditions at different vaginal apertures and during repeated dynamic cyclic stretching. The active contribution of tone was characterized using the ratio between EMG in a static position and during stretching and the proportion of women presenting PFM activation during stretching. Contribution of the passive component was evaluated using resting forces, stiffness, and hysteresis in women sustaining a negligible EMG signal during stretching. PFM contractility, such as strength, speed of contraction, coordination, and endurance, also was assessed during voluntary isometric efforts. Greater PFM resting forces and stiffness were found in women with PVD compared with controls, indicating an increased general tone. An increased active component also was found in women with PVD because they presented a superior EMG ratio, and a larger proportion of them presented PFM activation during stretching. Higher passive properties also were found in women with PVD. Women with PVD also showed decreased strength, speed of contraction, coordination, and endurance compared with controls. Findings provide further evidence of the contribution of PFM alterations in the etiology of PVD. These alterations should be

  7. Do KV7.1 channels contribute to control of arterial vascular tone?

    Science.gov (United States)

    Tsvetkov, Dmitry; Kaßmann, Mario; Tano, Jean‐Yves; Chen, Lan; Schleifenbaum, Johanna; Voelkl, Jakob; Lang, Florian; Huang, Yu

    2016-01-01

    Background and Purpose KV7.1 voltage‐gated potassium channels are expressed in vascular smooth muscle cells (VSMC) of diverse arteries, including mesenteric arteries. Based on pharmacological evidence using R‐L3 (KV7.1 channel opener), HMR1556, chromanol 293B (KV7.1 channel blockers), stimulation of these channels has been suggested to evoke profound relaxation in various vascular beds of rats. However, the specificity of these drugs in vivo is uncertain. Experimental Approach We used Kcnq1 −/− mice and pharmacological tools to determine whether KV7.1 channels play a role in the regulation of arterial tone. Key Results R‐L3 produced similar concentration‐dependent relaxations (EC50 ~ 1.4 μM) of arteries from wild‐type (Kcnq1 +/+) and Kcnq1 −/− mice, pre‐contracted with either phenylephrine or 60 mM KCl. This relaxation was not affected by 10 μM chromanol 293B, 10 μM HMR1556 or 30 μM XE991 (pan‐KV7 channel blocker). The anti‐contractile effects of the perivascular adipose tissue (PVAT) were normal in Kcnq1 −/− arteries. Chromanol 293B and HMR1556 did not affect the anti‐contractile effects of (PVAT). Isolated VSMCs from Kcnq1 −/− mice exhibited normal peak KV currents. The KV7.2–5 channel opener retigabine caused similar relaxations in Kcnq1 −/− and wild‐type vessels. Conclusion and Implications We conclude that KV7.1 channels were apparently not involved in the control of arterial tone by α1‐adrenoceptor agonists and PVAT. In addition, R‐L3 is an inappropriate pharmacological tool for studying the function of native vascular KV7.1 channels in mice. PMID:28000293

  8. Myocardial contractility in the echo lab: molecular, cellular and pathophysiological basis

    Directory of Open Access Journals (Sweden)

    Bombardini Tonino

    2005-09-01

    Full Text Available Abstract In the standard accepted concept, contractility is the intrinsic ability of heart muscle to generate force and to shorten, independently of changes in the preload or afterload with fixed heart rates. At molecular level the crux of the contractile process lies in the changing concentrations of Ca2+ ions in the myocardial cytosol. Ca2+ ions enter through the calcium channel that opens in response to the wave of depolarization that travels along the sarcolemma. These Ca2+ ions "trigger" the release of more calcium from the sarcoplasmic reticulum (SR and thereby initiate a contraction-relaxation cycle. In the past, several attempts were made to transfer the pure physiological concept of contractility, expressed in the isolated myocardial fiber by the maximal velocity of contraction of unloaded muscle fiber (Vmax, to the in vivo beating heart. Suga and Sagawa achieved this aim by measuring pressure/volume loops in the intact heart: during a positive inotropic intervention, the pressure volume loop reflects a smaller end-systolic volume and a higher end-systolic pressure, so that the slope of the pressure volume relationship moves upward and to the left. The pressure volume relationship is the most reliable index for assessing myocardial contractility in the intact circulation and is almost insensitive to changes in preload and after load. This is widely used in animal studies and occasionally clinically. The limit of the pressure volume relationship is that it fails to take into account the frequency-dependent regulation of contractility: the frequency-dependent control of transmembrane Ca2+ entry via voltage-gated Ca2+ channels provides cardiac cells with a highly sophisticated short-term system for the regulation of intracellular Ca2+ homeostasis. An increased stimulation rate increases the force of contraction: the explanation is repetitive Ca2+ entry with each depolarization and, hence, an accumulation of cytosolic calcium. As the heart

  9. Role of Lipoxygenase Metabolites of Arachidonic Acid in Enhanced Pulmonary Artery Contractions of Female Rabbits

    OpenAIRE

    Pfister, Sandra L.

    2011-01-01

    Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4 fold greater than that in men. Studies suggest sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared to ma...

  10. Testicular artery arising from an aberrant right renal artery | Suluba ...

    African Journals Online (AJOL)

    This case report we discovered the rare variation of the origin of the right testicular artery arising from the right aberrant renal artery with double renal artery irrigating both left and right kidneys. These variations in the testicular arteries and renal arteries have implication to surgical procedures such as orchidopexy repair for ...

  11. Duplicated middle cerebral artery

    Science.gov (United States)

    Perez, Jesus; Machado, Calixto; Scherle, Claudio; Hierro, Daniel

    2009-01-01

    Duplicated middle cerebral artery (DMCA) is an anomalous vessel arising from the internal carotid artery. The incidence DMCA is relatively law, and an association between this anomaly and cerebral aneurysms has been documented. There is a controversy whether DMCA may have perforating arteries. This is an important fact to consider in aneurysm surgery. We report the case of a 34-year-old black woman who suffered a subarachnoid hemorrhage and the angiography a left DMCA, and an aneurysm in an inferior branch of the main MCA. The DMCA and the MCA had perforating arteries. The aneurysm was clipped without complications. The observation of perforating arteries in our patient confirms that the DMCA may have perforating arteries. This is very important to be considered in cerebral aneurysms surgery. Moreover, the DMCA may potentially serve as a collateral blood supply to the MCA territory in cases of MCA occlusion. PMID:22140405

  12. Popliteal artery entrapment syndrome.

    LENUS (Irish Health Repository)

    O'Leary, D P

    2010-01-01

    Popliteal artery entrapment syndrome is a rare abnormality of the anatomical relationship between the popliteal artery and adjacent muscles or fibrous bands in the popliteal fossa. The following is a case report of a 19 year old female, in whom popliteal artery entrapment syndrome was diagnosed, and successfully treated surgically. A review of literature is also presented and provides details on how PAES is classified, diagnosed both clinically and radiologically, and treated surgically.

  13. Duplication of hepatic artery

    OpenAIRE

    Saeed Muhammad; Rufai Amin

    2001-01-01

    Background: The hepatic arterial anatomy is aberrant in almost 33-41% of individuals. The variant arterial anatomy recognized during routine cadaveric dissection offers great learning potential. Such findings provide an alternative perspective to view common morphology and its structural and functional importance. These impart the concept of patient individuality and subsequent individualization of medical and surgical therapies. Adequate knowledge of normal and abnormal arterial anat...

  14. Heritability of cilioretinal arteries

    DEFF Research Database (Denmark)

    Taarnhøj, Nina Charlotte; Munch, Inger C; Kyvik, Kirsten O

    2005-01-01

    of healthy monozygotic and dizygotic twins were examined using digital fundus photography and visual assessment of grayscale fundus photographs and color transparencies to detect the presence of cilioretinal arteries. RESULTS: Cilioretinal arteries were present in 45.1% of participants and 28.8% of eyes...... environmental factors. CONCLUSIONS: The presence or absence of one or more cilioretinal arteries in healthy persons is markedly influenced by genetic factors....

  15. GRK2 – A Link Between Myocardial Contractile Function and Cardiac Metabolism

    Science.gov (United States)

    Woodall, Meryl C.; Ciccarelli, Michele; Woodall, Benjamin P.; Koch, Walter J.

    2014-01-01

    Heart failure (HF) causes a tremendous burden on the worldwide healthcare system, affecting more than 23 million people. There are many cardiovascular disorders that contribute to the development of HF and multiple risk factors that accelerate its occurrence, but regardless of its underlying cause, HF is characterized by a marked decrease in myocardial contractility and loss of pump function. One biomarker molecule consistently shown to be upregulated in human HF and several animal models is G protein-coupled receptor (GPCR) kinase 2 (GRK2), a kinase originally discovered to be involved in GPCR desensitization, especially β-adrenergic receptors (βARs). Indeed, higher levels of GRK2 can impair βAR-mediated inotropic reserve and its inhibition or molecular reduction has shown to improve pump function in several animal models including a pre-clinical pig model of HF. Recently, non-classical roles for GRK2 in cardiovascular disease have been described, including negative regulation of insulin signaling, a role in myocyte cell survival and apoptotic signaling, and it has been shown to be localized in/on mitochondria. These new roles of GRK2 suggest that GRK2 may be a nodal link in the myocyte, influencing both cardiac contractile function and cell metabolism and survival and contributing to HF independent of its canonical role on GPCR desensitization. In this review, classical and non-classical roles for GRK2 will be discussed, focusing on recently discovered roles for GRK2 in cardiomyocyte metabolism and the effects that these roles may have on myocardial contractile function and HF development. PMID:24812353

  16. The role of apical contractility in determining cell morphology in multilayered epithelial sheets and tubes

    Science.gov (United States)

    Zhen Tan, Rui; Lai, Tanny; Chiam, K.-H.

    2017-08-01

    A multilayered epithelium is made up of individual cells that are stratified in an orderly fashion, layer by layer. In such tissues, individual cells can adopt a wide range of shapes ranging from columnar to squamous. From histological images, we observe that, in flat epithelia such as the skin, the cells in the top layer are squamous while those in the middle and bottom layers are columnar, whereas in tubular epithelia, the cells in all layers are columnar. We develop a computational model to understand how individual cell shape is governed by the mechanical forces within multilayered flat and curved epithelia. We derive the energy function for an epithelial sheet of cells considering intercellular adhesive and intracellular contractile forces. We determine computationally the cell morphologies that minimize the energy function for a wide range of cellular parameters. Depending on the dominant adhesive and contractile forces, we find four dominant cell morphologies for the multilayered-layered flat sheet and three dominant cell morphologies for the two-layered curved sheet. We study the transitions between the dominant cell morphologies for the two-layered flat sheet and find both continuous and discontinuous transitions and also the presence of multistable states. Matching our computational results with histological images, we conclude that apical contractile forces from the actomyosin belt in the epithelial cells is the dominant force determining cell shape in multilayered epithelia. Our computational model can guide tissue engineers in designing artificial multilayered epithelia, in terms of figuring out the cellular parameters needed to achieve realistic epithelial morphologies.

  17. Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy.

    Science.gov (United States)

    Mendias, Christopher L; Schwartz, Andrew J; Grekin, Jeremy A; Gumucio, Jonathan P; Sugg, Kristoffer B

    2017-03-01

    Skeletal muscle can adapt to increased mechanical loads by undergoing hypertrophy. Transient reductions in whole muscle force production have been reported during the onset of hypertrophy, but contractile changes in individual muscle fibers have not been previously studied. Additionally, the extracellular matrix (ECM) stores and transmits forces from muscle fibers to tendons and bones, and determining how the ECM changes during hypertrophy is important in understanding the adaptation of muscle tissue to mechanical loading. Using the synergist ablation model, we sought to measure changes in muscle fiber contractility, collagen content, and cross-linking, and in the expression of several genes and activation of signaling proteins that regulate critical components of myogenesis and ECM synthesis and remodeling during muscle hypertrophy. Tissues were harvested 3, 7, and 28 days after induction of hypertrophy, and nonoverloaded rats served as controls. Muscle fiber specific force (sF o ), which is the maximum isometric force normalized to cross-sectional area, was reduced 3 and 7 days after the onset of mechanical overload, but returned to control levels by 28 days. Collagen abundance displayed a similar pattern of change. Nearly a quarter of the transcriptome changed over the course of overload, as well as the activation of signaling pathways related to hypertrophy and atrophy. Overall, this study provides insight into fundamental mechanisms of muscle and ECM growth, and indicates that although muscle fibers appear to have completed remodeling and regeneration 1 mo after synergist ablation, the ECM continues to be actively remodeling at this time point. NEW & NOTEWORTHY This study utilized a rat synergist ablation model to integrate changes in single muscle fiber contractility, extracellular matrix composition, activation of important signaling pathways in muscle adaption, and corresponding changes in the muscle transcriptome to provide novel insight into the basic

  18. Role of the endocannabinoid system in the control of mouse myometrium contractility during the menstrual cycle.

    Science.gov (United States)

    Pagano, Ester; Orlando, Pierangelo; Finizio, Stefania; Rossi, Antonietta; Buono, Lorena; Iannotti, Fabio Arturo; Piscitelli, Fabiana; Izzo, Angelo A; Di Marzo, Vincenzo; Borrelli, Francesca

    2017-01-15

    Cannabis and ca