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Sample records for intrarenal renin-angiotensin system

  1. The adipose renin-angiotensin system modulates sysemic markers of insulin sensitivity activates the intrarenal renin-angiotensin system

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Suyeon [University of Tennessee, Knoxville (UTK); Soltani-Bejnood, Morvarid [University of Tennessee, Knoxville (UTK); Quignard-Boulange, Annie [Centre Biomedical des Cordeliers, Paris, France; Massiera, Florence [Centre de Biochimie, Nice, France; Teboul, Michele [Centre de Biochimie, Nice, France; Ailhaud, Gerard [Centre de Biochimie, Nice, France; Kim, Jung [University of Tennessee, Knoxville (UTK); Moustaid-Moussa, Naima [University of Tennessee, Knoxville (UTK); Voy, Brynn H [ORNL

    2006-07-01

    BACKGROUND: A growing body of data provides increasing evidence that the adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass. Beyond its paracrine actions within adipose tissue, adipocyte-derived angiotensin II (Ang II) may also impact systemic functions such as blood pressure and metabolism. METHODS AND RESULTS: We used a genetic approach to manipulate adipose RAS activity in mice and then study the consequences on metabolic parameters and on feedback regulation of the RAS. The models included deletion of the angiotensinogen (Agt) gene (Agt-KO), its expression solely in adipose tissue under the control of an adipocyte-specific promoter (aP2-Agt/ Agt-KO), and overexpression in adipose tissue of wild type mice (aP2-Agt). Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. Overexpression of Agt in adipose tissue resulted in increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also markedly elevated in kidney of aP2-Agt mice, suggesting that hypertension in these animals may be in part due to stimulation of the intrarenal RAS. CONCLUSIONS: Taken together, the results from this study demonstrate that alterations in adipose RAS activity significantly alter both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.

  2. Increased Dietary Salt Changes Baroreceptor Sensitivity and Intrarenal Renin-Angiotensin System in Goldblatt Hypertension.

    Science.gov (United States)

    Shimoura, Caroline G; Lincevicius, Gisele S; Nishi, Erika E; Girardi, Adriana C C; Simon, Karin A; Bergamaschi, Cassia T; Campos, Ruy R

    2017-01-01

    Renovascular hypertension (2-kidney 1-clip model (2K1C)) is characterized by renin-angiotensin system (RAS) activation. Increased Angiotensin II (AngII) leads to sympathoexcitation, oxidative stress, and alterations in sodium and water balance. The aim of this study was to evaluate whether a discrete increase in sodium chloride intake in 2K1C rats leads to changes in cardiovascular and autonomic function, oxidative stress, and renin angiotensin aldosterone system. After 4 weeks of induction of hypertension, rats were fed a normal sodium diet (0.4% NaCl) or a high-sodium diet (2% NaCl) for 2 consecutive weeks. Experiments were carried out for 6 weeks after clipping. Mean arterial pressure (MAP), renal sympathetic nerve activity (rSNA), arterial baroreflex control of rSNA, and heart rate (HR) were assessed. Thiobarbituric acid reactive substances and glutathione were measured as indicators of systemic oxidative stress. Angiostensin-converting enzyme (ACE), ACE2, and angiotensinogen were evaluated in clipped and unclipped kidneys as also urinary angiotensinogen and plasma renin activity. Angiotensinogen, plasma renin activity (PRA) and angiotensin-converting enzyme (ACE) and ACE2 in clipped and unclipped kidneys were evaluated. High-sodium diet did not change systemic oxidative stress, and basal values of MAP, HR, or rSNA; however, increased renal (-0.7±0.2 vs. -1.5±0.1 spikes/s/mm Hg) and cardiac (-0.9±0.14 vs. -1.5±0.14 bpm/mm Hg) baroreceptor reflex sensitivity in 2K1C rats. Although there was no alteration in PRA, a high-salt diet significantly decreased urinary angiotensinogen, ACE, and ACE2 expressions in the clipped and unclipped kidneys. Increased arterial baroreceptor control associated with a suppression of the intrarenal RAS in the 2K1C rats on high-salt diet provide a salt-resistant effect on hypertension and sympathoexcitation in renovascular hypertensive rats. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please

  3. Immunohistochemical expression of intrarenal renin angiotensin system components in response to tempol in rats fed a high salt diet.

    Science.gov (United States)

    Cao, Gabriel; Della Penna, Silvana Lorena; Kouyoumdzian, Nicolás Martín; Choi, Marcelo Roberto; Gorzalczany, Susana; Fernández, Belisario Enrique; Toblli, Jorge Eduardo; Rosón, María Inés

    2017-01-06

    To determine the effect of tempol in normal rats fed high salt on arterial pressure and the balance between antagonist components of the renal renin-angiotensin system. Sprague-Dawley rats were fed with 8% NaCl high-salt (HS) or 0.4% NaCl (normal-salt, NS) diet for 3 wk, with or without tempol (T) (1 mmol/L, administered in drinking water). Mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa) were measured. We evaluated angiotensin II (Ang II), angiotensin 1-7 (Ang 1-7), angiotensin converting enzyme 2 (ACE2), mas receptor (MasR), angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R) in renal tissues by immunohistochemistry. The intake of high sodium produced a slight but significant increase in MAP and differentially regulated components of the renal renin-angiotensin system (RAS). This included an increase in Ang II and AT1R, and decrease in ACE-2 staining intensity using immunohistochemistry. Antioxidant supplementation with tempol increased natriuresis and GFR, prevented changes in blood pressure and reversed the imbalance of renal RAS components. This includes a decrease in Ang II and AT1R, as increase in AT2, ACE2, Ang (1-7) and MasR staining intensity using immunohistochemistry. In addition, the natriuretic effects of tempol were observed in NS-T group, which showed an increased staining intensity of AT2, ACE2, Ang (1-7) and MasR. These findings suggest that a high salt diet leads to changes in the homeostasis and balance between opposing components of the renal RAS in hypertension to favour an increase in Ang II. Chronic antioxidant supplementation can modulate the balance between the natriuretic and antinatriuretic components of the renal RAS.

  4. The renin-angiotensin system in kidney development

    DEFF Research Database (Denmark)

    Jensen, B L; Stubbe, J; Madsen, K

    2004-01-01

    Recent data from studies in rodents with targeted gene disruption and pharmacological antagonists have shown that the renin-angiotensin-aldosterone system (RAAS) and cyclooxygenase type-2 (COX-2) are necessary for late stages of kidney development. The present review summarizes data on the develo......Recent data from studies in rodents with targeted gene disruption and pharmacological antagonists have shown that the renin-angiotensin-aldosterone system (RAAS) and cyclooxygenase type-2 (COX-2) are necessary for late stages of kidney development. The present review summarizes data...... on the developmental changes of RAAS and COX-2 and the pathways by which they are activated; their possible interplay and the mechanisms by which they affect kidney development. Intrarenal and circulating renin and angiotensin II (ANG II) are stimulated at birth in most mammals. In rats, renin and ANG II stay...

  5. The Renal Renin-Angiotensin System

    Science.gov (United States)

    Harrison-Bernard, Lisa M.

    2009-01-01

    The renin-angiotensin system (RAS) is a critical regulator of sodium balance, extracellular fluid volume, vascular resistance, and, ultimately, arterial blood pressure. In the kidney, angiotensin II exerts its effects to conserve salt and water through a combination of the hemodynamic control of renal blood flow and glomerular filtration rate and…

  6. Addition of hydrochlorothiazide to angiotensin receptor blocker therapy can achieve a lower sodium balance with no acceleration of intrarenal renin angiotensin system in patients with chronic kidney disease.

    Science.gov (United States)

    Fuwa, Daisuke; Fukuda, Michio; Ogiyama, Yoshiaki; Sato, Ryo; Mizuno, Masashi; Miura, Toshiyuki; Abe-Dohmae, Sumiko; Michikawa, Makoto; Kobori, Hiroyuki; Ohte, Nobuyuki

    2016-01-01

    Angiotensin receptor blockers (ARBs) produce a lower sodium (Na) balance, and the natriuretic effect is enhanced under Na deprivation, despite falls in blood pressure (BP) and glomerular filtration rate (GFR). The effect of additional hydrochlorothiazide (HCTZ; 12.5 mg/day) to ARB treatment (valsartan; 80 mg/day) on glomerulotubular Na balance was evaluated in 23 patients with chronic kidney disease. Add-on HCTZ decreased GFR, tubular Na load, and tubular Na reabsorption (t(Na)), although 24-hour urinary Na excretion (U(Na)V) remained constant. Daily urinary angiotensinogen excretion (U(AGT)V, 152±10→82±17 μg/g Cre) reduced (p=0.02). Changes in tubular Na load (r(2)=0.26) and t(Na) (r(2)=0.25) correlated with baseline 24-hour U(AGT)V. Changes in filtered Na load correlated with changes in nighttime systolic BP (r(2)=0.17), but not with changes in daytime systolic BP. The change in the t(Na) to filtered Na load ratio was influenced by the change in daytime U(Na)V (β=-0.67, F=16.8), rather than the change in nighttime U(Na)V. Lower Na balance was produced by add-on HCTZ to ARB treatment without an increase of intra-renal renin-angiotensin system activity, leading to restoration of nocturnal hypertension. A further study is needed to demonstrate that the reduction of U(AGT)V by additional diuretics to ARBs prevents the progression of nephropathy or cardiovascular events. © The Author(s) 2016.

  7. Classical Renin-Angiotensin system in kidney physiology.

    Science.gov (United States)

    Sparks, Matthew A; Crowley, Steven D; Gurley, Susan B; Mirotsou, Maria; Coffman, Thomas M

    2014-07-01

    The renin-angiotensin system has powerful effects in control of the blood pressure and sodium homeostasis. These actions are coordinated through integrated actions in the kidney, cardiovascular system and the central nervous system. Along with its impact on blood pressure, the renin-angiotensin system also influences a range of processes from inflammation and immune responses to longevity. Here, we review the actions of the "classical" renin-angiotensin system, whereby the substrate protein angiotensinogen is processed in a two-step reaction by renin and angiotensin converting enzyme, resulting in the sequential generation of angiotensin I and angiotensin II, the major biologically active renin-angiotensin system peptide, which exerts its actions via type 1 and type 2 angiotensin receptors. In recent years, several new enzymes, peptides, and receptors related to the renin-angiotensin system have been identified, manifesting a complexity that was previously unappreciated. While the functions of these alternative pathways will be reviewed elsewhere in this journal, our focus here is on the physiological role of components of the "classical" renin-angiotensin system, with an emphasis on new developments and modern concepts. © 2014 American Physiological Society.

  8. The Protective Arm of the Renin Angiotensin System (RAS)

    DEFF Research Database (Denmark)

    will become of major medical importance in the near future. Focusing on recent research, The Protective Arm of the Renin Angiotensin System presents a host of new experimental studies on specific components of the RAS, namely angiotensin AT2 receptors (AT2R), the angiotensin (1-7) peptide with its receptor...... understanding of the protective side of the Renin Angiotensin System (RAS) involving angiotensin AT2 receptor, ACE2, and Ang(1-7)/Mas receptor Combines the knowledge of editors who pioneered research on the protective renin angiotensin system including; Dr. Thomas Unger, one of the founders of AT2 receptor...... research; Dr. Ulrike M. Steckelings, who contributed significantly to first preclinical studies with a novel specific AT2-agonist, and Dr. Robson Santos who pioneered research on angiotensin-(1-7) and its receptor Mas. Shows that the protective RAS axes are able to ameliorate the course of several...

  9. Effect of Dual Blockade of Renin-Angiotensin Aldosterone System ...

    African Journals Online (AJOL)

    Original Research Article. Effect of Dual Blockade of Renin-Angiotensin Aldosterone. System on Proteinuria in Patients with Diabetic. Nephropathy and Advanced Azotemia. Hatice Odabas1, İlyas Capoglu2, Ramazan Cetinkaya3, Ali Riza Odabas3,. Abdullah Uyanik3 and Mustafa Keles3*. 1Department of Internal Medicine, ...

  10. The renin-angiotensin system and aging in the kidney

    OpenAIRE

    Yoon, Hye Eun; Choi, Bum Soon

    2014-01-01

    Aging is associated with progressive functional deterioration and structural changes in the kidney. Changes in the activity or responsiveness of the renin-angiotensin system (RAS) occur with aging. RAS changes predispose the elderly to various fluid and electrolyte imbalances as well as acute kidney injury and chronic kidney disease. Among the multiple pathways involved in renal aging, the RAS plays a central role. This review summarizes the association of the RAS with structural and function...

  11. Independent regulation of renin-angiotensin-aldosterone system in the kidney.

    Science.gov (United States)

    Nishiyama, Akira; Kobori, Hiroyuki

    2018-03-29

    Renin-angiotensin-aldosterone system (RAAS) plays important roles in regulating renal hemodynamics and functions, as well as in the pathophysiology of hypertension and renal disease. In the kidney, angiotensin II (Ang II) production is controlled by independent multiple mechanisms. Ang II is compartmentalized in the renal interstitial fluid with much higher concentrations than those existing in the circulation. Inappropriate activation of the intrarenal RAAS is an important contributor to the pathogenesis of hypertension and renal injury. It has been revealed that intrarenal Ang II levels are predominantly regulated by angiotensinogen and therefore, urinary angiotensinogen could be a biomarker for intrarenal Ang II generation. In addition, recent studies have demonstrated that aldosterone contributes to the progression of renal injury via direct actions on glomerular podocytes, mesangial cells, proximal tubular cells and tubulo-interstitial fibroblasts through the activation of locally expressed mineralocorticoid receptor. Thus, it now appears that intrarenal RAAS is independently regulated and its inappropriate activation contributes to the pathogenesis of the development of hypertension and renal disease. This short review article will focus on the independent regulation of the intrarenal RAAS with an emphasis on the specific role of angiotensinogen.

  12. The renin-angiotensin system and aging in the kidney.

    Science.gov (United States)

    Yoon, Hye Eun; Choi, Bum Soon

    2014-05-01

    Aging is associated with progressive functional deterioration and structural changes in the kidney. Changes in the activity or responsiveness of the renin-angiotensin system (RAS) occur with aging. RAS changes predispose the elderly to various fluid and electrolyte imbalances as well as acute kidney injury and chronic kidney disease. Among the multiple pathways involved in renal aging, the RAS plays a central role. This review summarizes the association of the RAS with structural and functional changes in the aging kidney and age-related renal injury, and describes the underlying mechanisms of RAS-related renal aging. An improved understanding of the renal aging process may lead to better individualized care of the elderly and improved renal survival in age-related diseases.

  13. Effects of dual renin-angiotensin system blockade on proteinuria in a ...

    African Journals Online (AJOL)

    Kidney diseases manifesting as proteinuria or elevated creatinine are increasingly prevalent complications of HIV infection. We report the effects of dual renin-angiotensin system blockade on proteinuria in a hypertensive black African HIV-infected patient.

  14. The importance of the renin-angiotensin system in normal cardiovascular homeostasis

    Science.gov (United States)

    Haber, E.

    1975-01-01

    Studies were carried out on adult mongrel dogs (20 to 30 kilograms) to investigate the importance of the renin-angiotensin system. Results indicate that the renin-angiotensin system plays a major role in the maintenance of circulatory homeostasis when extracellular fluid volume is depleted. It was also found that angiotensin II concentration, in addition to renal perfusion pressure, is a factor in the regulation of renin release.

  15. Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels

    OpenAIRE

    Zhang, Zhen-Ye; Qian, Ling-Ling; Wang, Ru-Xing

    2017-01-01

    Large-conductance calcium-activated potassium channels (BK channels) belong to a family of Ca2+-sensitive voltage-dependent potassium channels and play a vital role in various physiological activities in the human body. The renin-angiotensin-aldosterone system is acknowledged as being vital in the body's hormone system and plays a fundamental role in the maintenance of water and electrolyte balance and blood pressure regulation. There is growing evidence that the renin-angiotensin-aldosterone...

  16. Renin-angiotensin system gene expression and neurodegenerative diseases.

    Science.gov (United States)

    Goldstein, Benjamin; Speth, Robert C; Trivedi, Malav

    2016-07-01

    Single nucleotide polymorphisms and altered gene expression of components of the renin-angiotensin system (RAS) are associated with neurodegenerative diseases. Drugs that interact with the RAS have been shown to affect the course of neurodegenerative disease, suggesting that abnormalities in the RAS may contribute to neurodegenerative disease. A meta-analysis of genome-wide association studies and gene expression data for 14 RAS-related proteins was carried out for five neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, narcolepsy, amyotrophic lateral sclerosis and multiple sclerosis. No single nucleotide polymorphisms in any of the 14 RAS-related protein genes were significantly associated with the five neurodegenerative diseases investigated. There was an inverse association between expression of ATP6AP2, which encodes the (pro)renin receptor, and multiple sclerosis, Alzheimer's disease and Parkinson's disease. An association of AGTR, which encodes the AT1 angiotensin II receptor, and Parkinson's disease and Alzheimer's disease was also observed. To date, no single nucleotide polymorphisms in components of the RAS can be definitively linked to the neurodegenerative diseases evaluated in this study. However, altered gene expression of several components of the RAS is associated with several neurodegenerative diseases, which may indicate that the RAS contributes to the pathology of these diseases. © The Author(s) 2016.

  17. Renin angiotensin system and gender differences in dopaminergic degeneration

    Directory of Open Access Journals (Sweden)

    Rodriguez-Perez Ana I

    2011-08-01

    Full Text Available Abstract Background There are sex differences in dopaminergic degeneration. Men are approximately two times as likely as premenopausal women of the same age to develop Parkinson's disease (PD. It has been shown that the local renin angiotensin system (RAS plays a prominent role in sex differences in the development of chronic renal and cardiovascular diseases, and there is a local RAS in the substantia nigra and dopaminergic cell loss is enhanced by angiotensin via type 1 (AT1 receptors. Results In the present study, we observed that intrastriatal injection of 6-hydroxydopamine induced a marked loss of dopaminergic neurons in the substantia nigra of male rats, which was significantly higher than the loss induced in ovariectomized female rats given estrogen implants (i.e. rats with estrogen. However, the loss of dopaminergic neurons was significantly lower in male rats treated with the AT1 antagonist candesartan, and similar to that observed in female rats with estrogen. The involvement of the RAS in gender differences in dopaminergic degeneration was confirmed with AT1a-null mice lesioned with the dopaminergic neurotoxin MPTP. Significantly higher expression of AT1 receptors, angiotensin converting enzyme activity, and NADPH-oxidase complex activity, and much lower levels of AT2 receptors were observed in male rats than in female rats with estrogen. Conclusions The results suggest that brain RAS plays a major role in the increased risk of developing PD in men, and that manipulation of brain RAS may be an efficient approach for neuroprotective treatment of PD in men, without the feminizing effects of estrogen.

  18. The renin-angiotensin system: a possible new target for depression.

    Science.gov (United States)

    Vian, João; Pereira, Círia; Chavarria, Victor; Köhler, Cristiano; Stubbs, Brendon; Quevedo, João; Kim, Sung-Wan; Carvalho, André F; Berk, Michael; Fernandes, Brisa S

    2017-08-01

    Depression remains a debilitating condition with an uncertain aetiology. Recently, attention has been given to the renin-angiotensin system. In the central nervous system, angiotensin II may be important in multiple pathways related to neurodevelopment and regulation of the stress response. Studies of drugs targeting the renin-angiotensin system have yielded promising results. Here, we review the potential beneficial effects of angiotensin blockers in depression and their mechanisms of action. Drugs blocking the angiotensin system have efficacy in several animal models of depression. While no randomised clinical trials were found, case reports and observational studies showed that angiotensin-converting enzyme inhibitors or angiotensin receptor blockers had positive effects on depression, whereas other antihypertensive agents did not. Drugs targeting the renin-angiotensin system act on inflammatory pathways implicated in depression. Both preclinical and clinical data suggest that these drugs possess antidepressant properties. In light of these results, angiotensin system-blocking agents offer new horizons in mood disorder treatment.

  19. Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels

    Directory of Open Access Journals (Sweden)

    Zhen-Ye Zhang

    2017-09-01

    Full Text Available Large-conductance calcium-activated potassium channels (BK channels belong to a family of Ca2+-sensitive voltage-dependent potassium channels and play a vital role in various physiological activities in the human body. The renin-angiotensin-aldosterone system is acknowledged as being vital in the body's hormone system and plays a fundamental role in the maintenance of water and electrolyte balance and blood pressure regulation. There is growing evidence that the renin-angiotensin-aldosterone system has profound influences on the expression and bioactivity of BK channels. In this review, we focus on the molecular mechanisms underlying the regulation of BK channels mediated by the renin-angiotensin-aldosterone system and its potential as a target for clinical drugs.

  20. Angiotensin-(1-7) is a modulator of the human renin-angiotensin system

    NARCIS (Netherlands)

    Roks, AJM; van Geel, PP; Pinto, YM; Buikema, H; Henning, RH; de Zeeuw, D; van Gilst, WH

    The renin-angiotensin system is important for cardiovascular homeostasis. Currently, therapies for different cardiovascular diseases are based on inhibition of angiotensin-converting enzyme (ACE) or angiotensin II receptor blockade. Inhibition of ACE blocks metabolism of angiotensin-(1-7) to

  1. Angiotensin-(1-7) is a modulator of the human renin-angiotensin system

    NARCIS (Netherlands)

    Roks, A. J.; van Geel, P. P.; Pinto, Y. M.; Buikema, H.; Henning, R. H.; de Zeeuw, D.; van Gilst, W. H.

    1999-01-01

    The renin-angiotensin system is important for cardiovascular homeostasis. Currently, therapies for different cardiovascular diseases are based on inhibition of angiotensin-converting enzyme (ACE) or angiotensin II receptor blockade. Inhibition of ACE blocks metabolism of angiotensin-(1-7) to

  2. Functional interactions between 7TM receptors in the renin-angiotensin system--dimerization or crosstalk?

    DEFF Research Database (Denmark)

    Lyngsø, Christina; Erikstrup, Niels; Hansen, Jakob L

    2008-01-01

    The Renin-Angiotensin System (RAS) is important for the regulation of cardiovascular physiology, where it controls blood pressure, and salt- and water homeostasis. Dysregulation of RAS can lead to severe diseases including hypertension, diabetic nephropathy, and cardiac arrhythmia, and -failure...

  3. Cardiac repolarization during hypoglycaemia in type 1 diabetes: impact of basal renin-angiotensin system activity

    DEFF Research Database (Denmark)

    Due-Andersen, Rikke; Høi-Hansen, Thomas; Larroude, Charlotte Ellen

    2008-01-01

    AIMS: Hypoglycaemia-induced cardiac arrhythmias may be involved in the pathogenesis of the 'dead-in-bed syndrome' in patients with type 1 diabetes. Evidence suggests that the renin-angiotensin system (RAS) influences the occurrence of arrhythmias. The aim of this study was to explore if basal RAS...

  4. Structural adaptation to ischemia in skeletal muscle: effects of blockers of the renin-angiotensin system

    NARCIS (Netherlands)

    Scheidegger, K. J.; Nelissen-Vrancken, M. H.; Leenders, P. J.; Daemen, M. J.; Smits, J. F.; Wood, J. M.

    1997-01-01

    To investigate the effects of long-term treatment with blockers of the renin-angiotensin system on capillarization and growth of fibers in ischemic hind-limb muscles and in muscles under normal growth conditions. Ischemia was induced by partial ligation of the left common iliac artery. Ischemia

  5. Hemodynamic, morphometric and autonomic patterns in hypertensive rats - renin-angiotensin system modulation

    Directory of Open Access Journals (Sweden)

    Fernanda S. Zamo

    2010-01-01

    Full Text Available BACKGROUND: Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system. AIMS: To investigate the effects of the time-course of hypertension over 1 hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate; 2 left ventricular hypertrophy; and 3 local and systemic Renin-angiotensin system of the spontaneously hypertensive rats. METHODS: Male spontaneously hypertensive rats were randomized into two groups: young (n=13 and adult (n=12. Hemodynamic signals (blood pressure, heart rate, blood pressure variability (BPV and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g, by myocyte diameter (μm and by relative fibrosis area (RFA, %. ACE and ACE2 activities were measured by fluorometry (UF/min, and plasma renin activity (PRA was assessed by a radioimmunoassay (ng/mL/h. Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU. RESULTS: The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components. CONCLUSIONS: The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent

  6. The role of renin angiotensin system intervention in stage B heart failure.

    LENUS (Irish Health Repository)

    Collier, Patrick

    2012-04-01

    This article outlines the link between the renin angiotensin aldosterone system (RAAS) and various forms of cardiomyopathy, and also reviews the understanding of the effectiveness of RAAS intervention in this phase of ventricular dysfunction. The authors focus their discussion predominantly on patients who have had previous myocardial infarction or those who have left ventricular hypertrophy and also briefly discuss the role of RAAS activation and intervention in patients with alcoholic cardiomyopathy.

  7. MATHEMATICAL MODEL FOR THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM IN PATIENTS

    OpenAIRE

    Dr. T. Geetha; K. Balamurugan

    2016-01-01

    In this paper we use mathematical model for the application of The Renin-Angiotensin-Aldosterone system the difference of sleep related activity of the RAAS between depressed patients and healthy controls. We studied the nocturnal plasma concentration of ACTH, cortisol, renin and aldosterone, and sleep EEG in 7 medication free patients with depression. The huge increase in aldosterone in depressed subjects compared to controls and the unchanged cross correlation between the time course of noc...

  8. Cardiac repolarization during hypoglycaemia and hypoxaemia in healthy males: impact of renin-angiotensin system activity

    DEFF Research Database (Denmark)

    Due-Andersen, Rikke; Høi-Hansen, Thomas; Olsen, Niels Vidiendal

    2008-01-01

    AIMS: Activity in the renin-angiotensin system (RAS) may influence the susceptibility to cardiac arrhythmia. To study the effect of basal RAS activity on cardiac repolarization during myocardial stress induced by hypoglycaemia or hypoxaemia in healthy humans. METHODS AND RESULTS: Ten subjects...... with high RAS activity and 10 subjects with low RAS activity were studied on three different occasions: (i) hypoglycaemia (nadir P-glucose 2.7 +/- 0.5 mmol/L), (ii) hypoxaemia (nadir pO(2) 5.8 +/- 0.5 kPa), and (iii) normoglycaemic normoxia (control day). QT parameters were registered by Holter monitoring...

  9. The renin-angiotensin system; development and differentiation of the renal medulla

    DEFF Research Database (Denmark)

    Madsen, Kirsten; Robdrup Tinning, Anne; Marcussen, Niels

    2013-01-01

    Adverse events during fetal development can predispose the individual for cardiovascular disease later in life, a correlation known as fetal programming of adult hypertension. The "programming" events are not known but might reside in the kidneys due to these organs significant role...... on mechanisms of postnatal development the renal medulla and putting medullary developmental lesions into perspective with regard to the programming effect. Moreover, the renin-angiotensin system is critically involved in mammalian kidney development and signaling disorders give rise to developmental renal...

  10. Severe hypoglycaemia in type 1 diabetes: impact of the renin-angiotensin system and other risk factors

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik

    2009-01-01

    this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could contribute to improved prediction of, and inspire...... targets and thereby open for prevention of severe hypoglycaemia. Furthermore, subjects with elevated renin-angiotensin system activity and a high rate of severe hypoglycaemia might benefit from pharmacological blockade of the renin-angiotensin system by ACE inhibitors or angiotensin II receptor blockers...

  11. A Study on Renin-Angiotensin System and Total Exchangeable Sodium in Hypertension

    International Nuclear Information System (INIS)

    Choe, Kang Won; Park, Jung Sik; Lee, Jung Sang; Koh, Chang Soon

    1976-01-01

    The etiologic role of renin-angiotensin system and sodium-volume status in the pathophysiology of various forms of hypertension was investigated. Plasma renin activity (PRA) was measured by radioimmunoassay, while sodium-volume status was evaluated by the determination of total exchangeable sodium(NaE) using isotope dilution method. The subjects consisted of 25 controls, 24 patients with essential hypertension, 22 patients with chronic renal failure (13 with hypertension, 9 without hypertension) and 14 patients with malignant hypertension. The results were as follows: 1) An inverse correlation between NaE and PRA was noted in control subjects (r=-0.598, p 0.1) 3) Absolute value of PRA was not deviated significantly from control group (2.53±1.416 ng/ml/hr) except in malignant hypertension (6.09±2.042, p 0.1). It is suggested that renin-angiotensin system plays a predominant role in the pathogenesis of malignant hypertension and in hypertension of chronic renal failure, though sodium retention is also contributing factor. PRA variation in essential hypertension does not appear to be associated with any consistent change in Na-volume status, suggesting the existence of another mechanism in the genesis of hypertension and PRA variation.

  12. Involvement of renin-angiotensin system in hypertensive effect of cadmium in rats.

    Science.gov (United States)

    Lall, S B; Peshin, S S; Gulati, K; Khattar, S; Das, N; Seth, S D

    1997-04-01

    Role of renin-angiotensin system in hypertension induced by cadmium chloride (CdCl2) in rats has been investigated. Intravenous administration of CdCl (1 mg/kg) produced a biphasic response i.e. a transient fall followed by a marked and consistent rise in blood pressure. The peak hypertensive effect was accompanied by raised PRA levels. Pretreatment with captopril (1 mg/kg, i.v.) losartan (1 mg/kg, i.v.) or captopril + losartan attenuated the pressor response to Cd by 62%, 42% and 100% respectively in separate groups. Central administration of Cd (10 micrograms/rat, i.c.v.) showed a biphasic response similar to that observed after i.v. route. However, it was not accompanied by raised PRA levels. Prior treatment with losartan (10 micrograms/rat, i.c.v.) completely abolished the pressor response to Cd (i.c.v.) whereas it was not affected significantly by captopril (10 micrograms/rat, i.c.v.). On the other hand, centrally administered losartan only partially reduced the pressor response to i.v. Cd. The results are discussed in light of a differential involvement of central vs peripheral renin-angiotensin system in the hypertensive effect of Cd.

  13. Modulation of the renin-angiotensin system by food protein ...

    African Journals Online (AJOL)

    Chibuike

    derived BAPs can promote their use as safe antihypertensive agents. Moreover, future studies are needed to elucidate the long-term systemic molecular interactions of antihypertensive BAPs with the human genome, proteome and other cellular ...

  14. Gene-load score of the renin-angiotensin-aldosterone system is associated with coronary heart disease in familial hypercholesterolaemia

    NARCIS (Netherlands)

    van der Net, Jeroen B.; van Etten, Jeroen; Yazdanpanah, Mojgan; Dallinga-Thie, Geesje M.; Kastelein, John J. P.; Defesche, Joep C.; Koopmans, Richard P.; Steyerberg, Ewout W.; Sijbrands, Eric J. G.

    2008-01-01

    AIMS: Familial hypercholesterolaemia (FH) is characterized by premature coronary heart disease (CHD). However, the incidence of CHD varies considerably among FH patients. Genetic variation in the renin-angiotensin-aldosterone system (RAAS) and the adrenalin/noradrenalin system may be of importance

  15. The renin-angiotensin system in malignant hypertension revisited: plasma renin activity, microangiopathic hemolysis, and renal failure in malignant hypertension

    NARCIS (Netherlands)

    van den Born, Bert-Jan H.; Koopmans, Richard P.; van Montfrans, Gert A.

    2007-01-01

    BACKGROUND: Malignant hypertension is a renin-dependent form of hypertension. However, the variations in renin-angiotensin system (RAS) activation in malignant hypertension are not completely understood. A proposed mechanism for ongoing RAS activation is the presence of microangiopathic hemolysis

  16. Genetic variation and activity of the renin-angiotensin system and severe hypoglycemia in type 1 diabetes

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik; Dhamrait, Sukhbir S.; Sethi, Amar A

    2008-01-01

    BACKGROUND: The deletion-allele of the angiotensin-converting enzyme (ACE) gene and elevated ACE activity are associated with increased risk of severe hypoglycemia in type 1 diabetes. We explored whether genetic and phenotypic variations in other components of the renin-angiotensin system are sim...

  17. Angiotensin-converting enzyme 2, Angiotensin-(1-7) and Mas: new players of the Renin Angiotensin System

    DEFF Research Database (Denmark)

    Santos, Robson AS; Ferreira, Anderson J; Verano-Braga, Thiago

    2013-01-01

    Angiotensin(Ang)-(1-7) is now recognized as a biologically active component of renin-angiotensin system (RAS). Ang-(1-7) appears to play a central role in the RAS because it exerts a vast array of actions, many of them opposite to those attributed to the main effector peptide of the RAS, Ang II. ...

  18. Individual titration for maximal blockade of the renin-angiotensin system in proteinuric patients: A feasible strategy?

    NARCIS (Netherlands)

    Vogt, Liffert; Navis, Ger Jan; de Zeeuw, Dick

    2005-01-01

    Agents that interfere with the renin-angiotensin system (RAS) reduce proteinuria and afford renal protection. The combination of different measures that serve maximization of RAS blockade is thought to improve the antiproteinuric efficacy. The feasibility and the efficacy of such a combination

  19. Individual titration for maximal blockade of the renin-angiotensin system in proteinuric patients: a feasible strategy?

    NARCIS (Netherlands)

    Vogt, Liffert; Navis, Gerjan; de Zeeuw, Dick

    2005-01-01

    Agents that interfere with the renin-angiotensin system (RAS) reduce proteinuria and afford renal protection. The combination of different measures that serve maximization of RAS blockade is thought to improve the antiproteinuric efficacy. The feasibility and the efficacy of such a combination

  20. Between-patient differences in the renal response to renin-angiotensin system intervention : clue to optimising renoprotective therapy?

    NARCIS (Netherlands)

    Laverman, GD; de Zeeuw, D; Navis, G

    2002-01-01

    Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II (Ang II), AT(1)-receptor blockers (ARB) is the cornerstone of renoprotective therapy. Still, the number of patients with end-stage renal disease is increasing worldwide,

  1. Cardiac remodeling during and after renin-angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats

    DEFF Research Database (Denmark)

    Heijnen, Bart Fj; Pelkmans, Leonie Pj; Danser, Ah Jan

    2013-01-01

    This study investigated renin-angiotensin system (RAS)-induced cardiac remodeling and its reversibility in the presence and absence of high blood pressure (BP) in Cyp1a1-Ren2 transgenic inducible hypertensive rats (IHR). In IHR (pro)renin levels and BP can be dose-dependently titrated by oral...

  2. Inflammatory Renin-Angiotensin System Disruption Attenuates Sensory Hyperinnervation and Mechanical Hypersensitivity in a Rat Model of Provoked Vestibulodynia.

    Science.gov (United States)

    Chakrabarty, Anuradha; Liao, Zhaohui; Mu, Ying; Smith, Peter G

    2018-03-01

    Vestibulodynia is characterized by perivaginal mechanical hypersensitivity, hyperinnervation, and abundant inflammatory cells expressing renin-angiotensin system proteins. We developed a tractable rat model of vestibulodynia to further assess the contributions of the renin-angiotensin system. Complete Freund's adjuvant injected into the posterior vestibule induced marked vestibular hypersensitivity throughout a 7-day test period. Numbers of axons immunoreactive for PGP9.5, calcitonin gene-related peptide, and GFRα2 were increased. Numbers of macrophages and T cells were also increased whereas B cells were not. Renin-angiotensin-associated proteins were abundant, with T cells as well as macrophages contributing to increased renin and angiotensinogen. Media conditioned with inflamed vestibular tissue promoted neurite sprouting by rat dorsal root ganglion neurons in vitro, and this was blocked by the angiotensin II receptor type 2 receptor antagonist PD123319 or by an angiotensin II function blocking antibody. Sensory axon sprouting induced by inflamed tissue was dependent on activity of angiotensin-converting enzyme or chymase, but not cathepsin G. Thus, vestibular Complete Freund's adjuvant injection substantially recapitulates changes seen in patients with provoked vestibulodynia, and shows that manipulation of the local inflammatory renin-angiotensin system may be a useful therapeutic strategy. This study provides evidence that inflammation of the rat vestibule induces a phenotype recapitulating behavioral and cytological features of human vestibulodynia. The model confirms a crucial role of the local inflammatory renin-angiotensin system in hypersensitivity and hyperinnervation. Targeting this system holds promise for developing new nonopioid analgesic treatment strategies. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.

  3. Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension

    Science.gov (United States)

    De Man, Frances; Tu, Ly; Handoko, Louis; Rain, Silvia; Ruiter, Gerrina; François, Charlène; Schalij, Ingrid; Dorfmüller, Peter; Simonneau, Gérald; Fadel, Elie; Perros, Frederic; Boonstra, Anco; Postmus, Piet; Van Der Velden, Jolanda; Vonk-Noordegraaf, Anton; Humbert, Marc; Eddahibi, Saadia; Guignabert, Christophe

    2012-01-01

    Rationale Patients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems like renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system are upregulated but this may have long-term negative effects on the progression of iPAH. Objectives Assess systemic and pulmonary RAAS-activity in iPAH-patients and determine the efficacy of chronic RAAS-inhibition in experimental PAH. Measurements and Main Results We collected 79 blood samples from 58 iPAH-patients in the VU University Medical Center Amsterdam (between 2004–2010), to determine systemic RAAS-activity. We observed increased levels of renin, angiotensin (Ang) I and AngII, which was associated with disease progression (p<0.05) and mortality (p<0.05). To determine pulmonary RAAS-activity, lung specimens were obtained from iPAH-patients (during lung transplantation, n=13) and controls (during lobectomy or pneumonectomy for cancer, n=14). Local RAAS-activity in pulmonary arteries of iPAH-patients was increased, demonstrated by elevated ACE-activity in pulmonary endothelial cells and increased AngII type 1 (AT1) receptor expression and signaling. In addition, local RAAS- upregulation was associated with increased pulmonary artery smooth muscle cell proliferation via enhanced AT1-receptor signaling in iPAH-patients compared to controls. Finally, to determine the therapeutic potential of RAAS-activity, we assessed the chronic effects of an AT1-receptor antagonist (losartan) in the monocrotaline PAH-rat model (60 mg/kg). Losartan delayed disease progression, decreased RV afterload and pulmonary vascular remodeling and restored right ventricular-arterial coupling in PAH-rats. Conclusions Systemic and pulmonary RAAS-activities are increased in iPAH-patients and associated with increased pulmonary vascular remodeling. Chronic inhibition of RAAS by losartan is beneficial in experimental PAH. PMID:22859525

  4. Current aspects of the interactions between dementia, the brain renin-angiotensin system and oxidative stress

    Directory of Open Access Journals (Sweden)

    Serban Dragomir

    2015-01-01

    Full Text Available There is increased interest in the interactions between vascular disorders and Alzheimer’s disease (AD. While initially these interactions were explained by the fact that these are both very common disorders, particularly later in life, recently, the possibility that these deficiencies might actually coexist is increasingly being questioned. This review attempts to present modern aspects and current reports regarding the interactions between AD, the renin-angiotensin system (RAS and hypertension, while also describing the relevance of antihypertensive drug use acting via the RAS in the treatment and prevention of AD, as well as the importance of oxidative stress, the alteration of the balance between antioxidants and pro-oxidants, in the interaction between AD and the RAS.

  5. Dual Blockade of the Renin-angiotensin-aldosterone System in Type 2 Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Yan-Huan Feng

    2016-01-01

    Full Text Available Objective: To examine the efficacy and safety of dual blockade of the renin-angiotensin-aldosterone system (RAAS among patients with type 2 diabetic kidney disease. Data Sources: We searched the major literature repositories, including the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE, for randomized clinical trials published between January 1990 and October 2015 that compared the efficacy and safety of the use of dual blockade of the RAAS versus the use of monotherapy, without applying any language restrictions. Keywords for the searches included "diabetic nephropathy," "chronic kidney disease," "chronic renal insufficiency," "diabetes mellitus," "dual therapy," "combined therapy," "dual blockade," "renin-angiotensin system," "angiotensin-converting enzyme inhibitor," "angiotensin-receptor blocker," "aldosterone blockade," "selective aldosterone blockade," "renin inhibitor," "direct renin inhibitor," "mineralocorticoid receptor blocker," etc. Study Selection: The selected articles were carefully reviewed. We excluded randomized clinical trials in which the kidney damage of patients was related to diseases other than diabetes mellitus. Results: Combination treatment with an angiotensin-converting enzyme inhibitor supplemented by an angiotensin II receptor blocking agent is expected to provide a more complete blockade of the RAAS and a better control of hypertension. However, existing literature has presented mixed results, in particular, related to patient safety. In view of this, we conducted a comprehensive literature review in order to explain the rationale for dual blockade of the RAAS, and to discuss the pros and cons. Conclusions: Despite the negative results of some recent large-scale studies, it may be immature to declare that the dual blockade is a failure because of the complex nature of the RAAS surrounding its diversified functions and utility. Further trials are warranted to study the combination therapy as an

  6. Renin-Angiotensin System Blockade Associated with Statin Improves Endothelial Function in Diabetics

    Directory of Open Access Journals (Sweden)

    Ronaldo Altenburg Gismondi

    2015-01-01

    Full Text Available AbstractBackground:Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness.Objective:To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness.Methods:Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring, endothelial function (brachial artery flow-mediated dilation, and vascular stiffness (pulse wave velocity were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively.Results:The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007, and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003 when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820. There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586.Conclusion:Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes.

  7. The renin angiotensin system in the development of cardiovascular disease: role of aliskiren in risk reduction

    Directory of Open Access Journals (Sweden)

    Paolo Verdecchia

    2008-10-01

    Full Text Available Paolo Verdecchia1, Fabio Angeli1, Giovanni Mazzotta1, Giorgio Gentile2, Gianpaolo Reboldi21Department of Cardiology, Clinical Research Unit ‘Preventive Cardiology’, Hospital ‘Santa Maria della Misericordia’, and Fondazione Umbra Cuore e Ipertensione – AUCI Onlus, Perugia, Italy; 2Department of Internal Medicine University of Perugia, ItalyAbstract: An association has been shown between plasma renin activity (PRA and the risk of cardiovascular disease. There is also evidence that angiotensin II exerts detrimental effects on progression and instabilization of atherosclerotic plaque. The renin-angiotensin system (RAS can be inhibited through inhibition of angiotensin I (Ang I generation from angiotensinogen by direct renin inhibitors, inhibition of angiotensin II (Ang II generation from angiotensin I by angiotensin-converting enzyme inhibitors and finally by direct inhibition of the action of Ang II receptor level. Aliskiren, the first direct renin inhibitor to reach the market, is a lowmolecular-weight, orally active, hydrophilic nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by Ang II on renin synthesis. Because of its long pharmacological half-life, aliskiren is suitable for once-daily administration. Its through-to-peak ratio approximates 98% for the 300 mg/day dose. Because of its mechanism of action, aliskiren might offer the additional opportunity to inhibit progression of atherosclerosis at tissue level. Hypertension is an approved indication for this drug, which is also promising for the treatment of heart failure. The efficacy of this drug in reducing major clinical events is being tested in large ongoing clinical trials.Keywords: plasma renin activity, renin angiotensin system, aliskiren, angiotensinogen, renin, hypertension, heart failure, diabetes

  8. Associations of renin-angiotensin system genetic polymorphisms and clinical course after aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

    Griessenauer, Christoph J; Tubbs, R Shane; Foreman, Paul M; Chua, Michelle H; Vyas, Nilesh A; Lipsky, Robert H; Lin, Mingkuan; Iyer, Ramaswamy; Haridas, Rishikesh; Walters, Beverly C; Chaudry, Salman; Malieva, Aisana; Wilkins, Samantha; Harrigan, Mark R; Fisher, Winfield S; Shoja, Mohammadali M

    2017-05-01

    OBJECTIVE Renin-angiotensin system (RAS) genetic polymorphisms are thought to play a role in cerebral aneurysm formation and rupture. The Cerebral Aneurysm Renin Angiotensin System (CARAS) study prospectively evaluated associations of common RAS polymorphisms and clinical course after aneurysmal subarachnoid hemorrhage (aSAH). METHODS The CARAS study prospectively enrolled aSAH patients at 2 academic centers in the United States. A blood sample was obtained from all patients for genetic evaluation and measurement of plasma angiotensin converting enzyme (ACE) concentration. Common RAS polymorphisms were detected using 5'exonuclease genotyping assays and pyrosequencing. Analysis of associations of RAS polymorphisms and clinical course after aSAH were performed. RESULTS A total of 166 patients were screened, and 149 aSAH patients were included for analysis. A recessive effect of allele I (insertion) of the ACE I/D (insertion/deletion) polymorphism was identified for Hunt and Hess grade in all patients (OR 2.76, 95% CI 1.17-6.50; p = 0.0206) with subsequent poor functional outcome. There was a similar effect on delayed cerebral ischemia (DCI) in patients 55 years or younger (OR 3.63, 95% CI 1.04-12.7; p = 0.0439). In patients older than 55 years, there was a recessive effect of allele A of the angiotensin II receptor Type 2 (AT2) A/C single nucleotide polymorphism (SNP) on DCI (OR 4.70, 95% CI 1.43-15.4; p = 0.0111). CONCLUSIONS Both the ACE I/D polymorphism and the AT2 A/C single nucleotide polymorphism were associated with an age-dependent risk of delayed cerebral ischemia, whereas only the ACE I/D polymorphism was associated with poor clinical grade at presentation. Further studies are required to elucidate the relevant pathophysiology and its potential implication in the treatment of patients with aSAH.

  9. Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY)

    DEFF Research Database (Denmark)

    Lindhardt, Morten; Persson, Frederik; Currie, Gemma

    2016-01-01

    INTRODUCTION: Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment...

  10. Severe hypoglycaemia in type 1 diabetes: impact of the renin-angiotensin system and other risk factors

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik

    2009-01-01

    this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could contribute to improved prediction of, and inspire...... targets and thereby open for prevention of severe hypoglycaemia. Furthermore, subjects with elevated renin-angiotensin system activity and a high rate of severe hypoglycaemia might benefit from pharmacological blockade of the renin-angiotensin system by ACE inhibitors or angiotensin II receptor blockers...... diabetes. The series of studies that constitute this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could...

  11. Prevention of microalbuminuria using early intervention with renin-angiotensin system inhibitors in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, Frederik; Lindhardt, Morten; Rossing, Peter

    2016-01-01

    Hypothesis/objectives: Early prevention of diabetic nephropathy by way of blocking the renin-angiotensin system (RAS) in patients with normoalbuminuria seems rational, but trials have so far shown conflicting results. The present meta-analysis was undertaken to investigate if such treatment can p......-cause mortality(p=0.07). Conclusions: We conclude that in patients with type 2 diabetes and normoalbuminuria, early intervention with ACEis or ARBs reduces the risk for development of microalbuminuria.......Hypothesis/objectives: Early prevention of diabetic nephropathy by way of blocking the renin-angiotensin system (RAS) in patients with normoalbuminuria seems rational, but trials have so far shown conflicting results. The present meta-analysis was undertaken to investigate if such treatment can...

  12. RETRACTED: Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy.

    Science.gov (United States)

    Zhou, Tian-Biao; Li, Hong-Yan; Jiang, Zong-Pei; Zhou, Jia-Fan; Huang, Miao-Fang; Zhou, Zhi-Yang

    2015-12-01

    The following article has been included in a multiple retraction: Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System ( JRAAS) 1470320314563424, first published 18 December 2014. DOI: 10.1177/1470320314563424 . This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the JRAAS (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer-review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online-first articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy JRAAS 1470320314563426, first published 18 December 2014. DOI: 10.1177/1470320314563426 . Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy JRAAS 1470320314563424, first published 18 December 2014. DOI: 10.1177/1470320314563424 . Weiqiang Zhong, Zongpei Jiang and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population JRAAS1470320314566019, first published 26 January 2015. DOI: 10.1177/1470320314566019 . Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into

  13. Radioimmunologic analysis of the state of the renin-angiotensin-aldosterone system in arterial hypertension

    International Nuclear Information System (INIS)

    Slavnov, V.N.; Yakovlev, A.A.; Gandzha, T.I.; Yugrinov, O.G.

    1986-01-01

    For 110 patients having various forms of arterial hypertension (hypertension, aldersteronoma, phaeochromocytoma, corticosteroma) the parameters of the system renin-angiotensin-aldosterone (RAA) were measured. Basal values of aldosterone and renin activity in blood were determined as well as their concentration in blood taken from the vena cava inferior, renal and adrenal veins during selective renography. The 24-hours rhythm of the hormones in the blood, the reaction of the glomerular zone of the adrenal cortex and the juxtaglomerular renal system under acute lasix stress was evaluated. It was found, that the system RAA is disturbed in all patients with arterial hypertension. This is indicated by changes of aldosterone concentration, renin activity in peripheral blood and in the blood from the vena cava inferior, renal and adrenal veins, the 24-hour rhythm of their concentrations in serum and the reaction to acute lasix stress. The radioimmunoassays of quantitative parameters of the RAA system are decisive for the differential diagnostics of hypertension and suprarenomas connected with a hypertension syndrome. They facilitate a rational choice of the hypertension therapy and the daily distribution of the medicaments for patients with hypertension. The radioimmunoassays can be used for checking the efficiency of medicaments and surgery. (author)

  14. Renin-angiotensin system: an old player with novel functions in skeletal muscle.

    Science.gov (United States)

    Cabello-Verrugio, Claudio; Morales, María Gabriela; Rivera, Juan Carlos; Cabrera, Daniel; Simon, Felipe

    2015-05-01

    Skeletal muscle is a tissue that shows the most plasticity in the body; it can change in response to physiological and pathological stimuli. Among the diseases that affect skeletal muscle are myopathy-associated fibrosis, insulin resistance, and muscle atrophy. A common factor in these pathologies is the participation of the renin-angiotensin system (RAS). This system can be functionally separated into the classical and nonclassical RAS axis. The main components of the classical RAS pathway are angiotensin-converting enzyme (ACE), angiotensin II (Ang-II), and Ang-II receptors (AT receptors), whereas the nonclassical axis is composed of ACE2, angiotensin 1-7 [Ang (1-7)], and the Mas receptor. Hyperactivity of the classical axis in skeletal muscle has been associated with insulin resistance, atrophy, and fibrosis. In contrast, current evidence supports the action of the nonclassical RAS as a counter-regulator axis of the classical RAS pathway in skeletal muscle. In this review, we describe the mechanisms involved in the pathological effects of the classical RAS, advances in the use of pharmacological molecules to inhibit this axis, and the beneficial effects of stimulation of the nonclassical RAS pathway on insulin resistance, atrophy, and fibrosis in skeletal muscle. © 2015 Wiley Periodicals, Inc.

  15. Involvement of Renin-Angiotensin System in Retinopathy of Prematurity - A Possible Target for Therapeutic Intervention.

    Directory of Open Access Journals (Sweden)

    Madhu Nath

    Full Text Available Examining the Retinal Renin Angiotensin System (RRAS in the ROP neonates and analyzing the possibility of modulating the RRAS to prevent the progression in Oxygen Induced Retinopathy (OIR model.Vitreous of ROP patients (n = 44, median age 5.5 months was quantified for RRAS components, VEGF, HIF-1α and compared with age matched control. The involvement of RRAS in ROP was tested in the rat model of OIR and compared with normoxia. Expressions of RAS components, VEGF and HIF-1α in retina were analyzed using qPCR and retinal structure and function was also analyzed. Effect of Angiotensin Converting Enzyme Inhibitor (ACEI and Angiotensin Receptor Blocker (ARB was evaluated and compared with Bevacizumab which served as a positive control. Drug penetration into retina was confirmed by liquid chromatography coupled ESI-tandem mass spectroscopy (LC-MS/MS.Multifold increase in the expression of RAS components in human vitreous and rat retina showed their involvement in ROP. ERG & fundus studies in OIR revealed the altered function of retina and were successfully prevented by ARB (telmisartan, ACEI (lisinopril and bevacizumab. Retinal analysis revealed the presence of ACEI and ARB in their therapeutic levels.This study for the first time demonstrates the upregulated level of RAS components in human ROP vitreous and further that the pharmacological intervention in RRAS can functionally and structurally preserve retina against the progression of ROP in the OIR model.

  16. Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System.

    Science.gov (United States)

    Weidemann, Benjamin J; Voong, Susan; Morales-Santiago, Fabiola I; Kahn, Michael Z; Ni, Jonathan; Littlejohn, Nicole K; Claflin, Kristin E; Burnett, Colin M L; Pearson, Nicole A; Lutter, Michael L; Grobe, Justin L

    2015-06-11

    Dietary fats and sodium are both palatable and are hypothesized to synergistically contribute to ingestive behavior and thereby obesity. Contrary to this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary sodium content. This suppressive effect of dietary sodium upon weight gain was mediated specifically through a reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism. Replacement of circulating angiotensin II levels reversed the effects of high dietary sodium to suppress digestive efficiency. While the AT1 receptor antagonist losartan had no effect in mice fed low sodium, the AT2 receptor antagonist PD-123,319 suppressed digestive efficiency. Correspondingly, genetic deletion of the AT2 receptor in FVB/NCrl mice resulted in suppressed digestive efficiency even on a standard chow diet. Together these data underscore the importance of digestive efficiency in the pathogenesis of obesity, and implicate dietary sodium, the renin-angiotensin system, and the AT2 receptor in the control of digestive efficiency regardless of mouse strain or macronutrient composition of the diet. These findings highlight the need for greater understanding of nutrient absorption control physiology, and prompt more uniform assessment of digestive efficiency in animal studies of energy balance.

  17. Role of Renin-Angiotensin System and Oxidative Stress on Vascular Inflammation in Insulin Resistence Model

    Directory of Open Access Journals (Sweden)

    N. F. Renna

    2013-01-01

    Full Text Available (1 This study aims to demonstrate the causal involvement of renin angiotensin system (RAS and oxidative stress (OS on vascular inflammation in an experimental model of metabolic syndrome (MS achieved by fructose administration to spontaneously hypertensive rats (FFHR during 12 weeks. (2 Chronic treatment with candesartan (C (10 mg/kg per day for the last 6 weeks or 4OH-Tempol (T (10−3 mmol/L in drinking water for the last 6 weeks reversed the increment in metabolic variables and systolic blood pressure. In addition, chronic C treatment reverted cardiovascular remodeling but not T. (3 Furthermore, chronic treatment with C was able to completely reverse the expression of NF-κB and VCAM-1, but T only reduced the expression. C reduced the expression of proatherogenic cytokines as CINC2, CINC3, VEGF, Leptin, TNF-alpha, and MCP-1 and also significantly reduced MIP-3, beta-NGF, and INF-gamma in vascular tissue in this experimental model. T was not able to substantially modify the expression of these cytokines. (4 The data suggest the involvement of RAS in the expression of inflammatory proteins at different vascular levels, allowing the creation of a microenvironment suitable for the creation, perpetuation, growth, and destabilization of vascular injury.

  18. Persistent phenotypic shift in cardiac fibroblasts: impact of transient renin angiotensin system inhibition.

    Science.gov (United States)

    Hale, Taben M

    2016-04-01

    Fibrotic cardiac remodeling ultimately leads to heart failure - a debilitating and costly condition. Select antihypertensive agents have been effective in reducing or slowing the development of cardiac fibrosis. Moreover, some experimental studies have shown that the reduction in fibrosis induced by these agents persists long after stopping treatment. What has not been as well investigated is whether this transient treatment results in a protection against future fibrotic cardiac remodeling. In the present review, previously published studies are re-examined to assess whether the relative percent increase in collagen deposition over an off-treatment period is attenuated, relative to control, following transient antihypertensive treatment in young or adult rats. Present findings suggest that transient inhibition of the renin angiotensin system (RAS) not only produces a sustained reduction in cardiac fibrosis, but also results in a degree of protection against future collagen deposition. In addition, prior transient RAS inhibition appears to alter the cardiac fibroblast phenotype such that these cells show a muted response to myocardial injury - namely reduced proliferation, chemokine release, and collagen deposition. This review puts forth several potential mechanisms underlying this long-term cardiac protection that is afforded by transient RAS inhibition. Specifically, fibroblast phenotypic change, cardiac fibroblast apoptosis, sustained suppression of the RAS, persistent reduction in left ventricular hypertrophy, and persistent reduction in arterial pressure are each discussed. Identifying the mechanisms ultimately responsible for this change in cardiac fibroblast response to injury, hypertension, and aging may reveal novel targets for therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. The role of the renin-angiotensin-aldosterone system in heart failure

    Directory of Open Access Journals (Sweden)

    Thomas Unger

    2004-03-01

    Full Text Available Activity of the renin-angiotensin-aldosterone system (RAAS is increased in patients with heart failure, and its maladaptive mechanisms may lead to adverse effects such as cardiac remodelling and sympathetic activation. Elevated renin activity has been demonstrated in patients with dilated cardiomyopathy. (Third-generation synthetic non-peptide renin inhibitors, with more favourable properties than earlier renin inhibitors, lower ambulatory blood pressure and may have a role to play in other cardiovascular disease. Chymase, a protease inhibitor stored in mast cells that generates angiotensin II (Ang II (in addition to angiotensin-converting enzyme [ACE], has been linked to extracellular matrix remodelling in heart failure. Again, chymase inhibitors have been developed to investigate its functions in vitro and in vivo. Bradykinin is thought to contribute to the cardioprotective effect of ACE inhibition through modification of nitric oxide release, calcium handling and collagen accumulation. Ang II is believed to influence a number of molecular and structural changes in the heart, mostly mediated through the AT1-receptor. The importance of the RAAS in heart failure is shown by the survival benefit conferred by treatment with ACE inhibitors.

  20. Renin-Angiotensin System Genes Polymorphisms and Essential Hypertension in Burkina Faso, West Africa

    Directory of Open Access Journals (Sweden)

    Daméhan Tchelougou

    2015-01-01

    Full Text Available Objective. This study aimed to investigate the association between three polymorphisms of renin-angiotensin system and the essential hypertension in the population of Burkina Faso. Methodology. This was a case-control study including 202 cases and 204 matched controls subjects. The polymorphisms were identified by a classical and a real-time PCR. Results. The AGT 235M/T and AT1R 1166A/C polymorphisms were not associated with the hypertension while the genotype frequencies of the ACE I/D polymorphism between patients and controls (DD: 66.83% and 35.78%, ID: 28.22% and 50.98%, II: 4.95% and 13.24%, resp. were significantly different (p < 10−4. The genotype DD of ACE gene (OR = 3.40, p < 0.0001, the increasing age (OR = 3.83, p < 0.0001, obesity (OR = 4.84, p < 0.0001, dyslipidemia (OR = 3.43, p = 0.021, and alcohol intake (OR = 2.76, p < 0.0001 were identified as the independent risk factors for hypertension by multinomial logistic regression. Conclusion. The DD genotype of the ACE gene is involved in susceptibility to hypertension. Further investigations are needed to better monitor and provide individualized care for hypertensive patients.

  1. Renin angiotensin system and cardiac hypertrophy after sinoaortic denervation in rats

    Directory of Open Access Journals (Sweden)

    Aline Cristina Piratello

    2010-01-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the role of angiotensin I, II and 1-7 on left ventricular hypertrophy of Wistar and spontaneously hypertensive rats submitted to sinoaortic denervation. METHODS: Ten weeks after sinoaortic denervation, hemodynamic and morphofunctional parameters were analyzed, and the left ventricle was dissected for biochemical analyses. RESULTS: Hypertensive groups (controls and denervated showed an increase on mean blood pressure compared with normotensive ones (controls and denervated. Blood pressure variability was higher in denervated groups than in their respective controls. Left ventricular mass and collagen content were increased in the normotensive denervated and in both spontaneously hypertensive groups compared with Wistar controls. Both hypertensive groups presented a higher concentration of angiotensin II than Wistar controls, whereas angiotensin 1-7 concentration was decreased in the hypertensive denervated group in relation to the Wistar groups. There was no difference in angiotensin I concentration among groups. CONCLUSION: Our results suggest that not only blood pressure variability and reduced baroreflex sensitivity but also elevated levels of angiotensin II and a reduced concentration of angiotensin 1-7 may contribute to the development of left ventricular hypertrophy. These data indicate that baroreflex dysfunction associated with changes in the renin angiotensin system may be predictive factors of left ventricular hypertrophy and cardiac failure.

  2. Sex differences in the aging pattern of renin-angiotensin system serum peptidases.

    Science.gov (United States)

    Fernández-Atucha, A; Izagirre, A; Fraile-Bermúdez, A B; Kortajarena, M; Larrinaga, G; Martinez-Lage, P; Echevarría, E; Gil, J

    2017-01-01

    Serum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin-angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. In the present study, serum activities of RAS peptidases were analyzed to evaluate the existence of sexual differences, with a possible different pattern in pre- and post-andropausal/post-menopausal participants. One hundred and eighteen healthy men and women between 41 and 70 years of age (58 women and 60 men) were recruited to participate in the study. Serum RAS-regulating enzymes were measured by spectrofluorimetry. Enzymatic activity was recorded as units of enzyme per milliliter of serum (U/mL). Significantly lower serum APA activity was observed in men with respect to women; no sex differences were detected for ACE, ACE2, NEP, or APN. Significantly lower APA and ACE serum activity were observed in older men compared to older women. In contrast, younger (menopausia, on the critical serum enzymatic activities of the RAS, which could correlate with sexual differences in cardiovascular risk.

  3. Combination inhibition of the renin-angiotensin system: is more better?

    Science.gov (United States)

    Krause, Michelle W; Fonseca, Vivian A; Shah, Sudhir V

    2011-08-01

    Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are considered the standard of care for treatment of cardiovascular disease and chronic kidney disease. Combination therapy with both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers effectively inhibits the renin-angiotensin system as well as potentiates the vasodilatory effects of bradykinin. It has been advocated that this dual blockade approach theoretically should result in improved clinical outcomes in both cardiovascular disease and chronic kidney disease. Clinical trial evidence for the use of combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in cardiovascular disease has provided conflicting results in hypertension, congestive heart failure, and ischemic heart disease. Clinical trial evidence to support combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chronic kidney disease has largely been based on proteinuria reduction as a surrogate marker for clinically meaningful outcomes. Recent large-scale randomized clinical trials have not been able to validate protection in halting progression in chronic kidney disease with a dual blockade approach. This review serves as an appraisal on the clinical evidence of combination angiotensin-converting enzyme inhibition and angiotensin II receptor blockade in both cardiovascular disease and chronic kidney disease.

  4. Contribution of the renin-angiotensin system in chronic foot-shock induced hypertension in rats.

    Science.gov (United States)

    Wang, Lin-Hui; Dong, Tao; Liu, Bei-Bei; Zhao, Xiao-Dong; Chen, Jing-Wei; Murao, Koji; Zhu, Wei; Zhang, Guo-Xing

    2015-01-15

    Chronic foot shock has been demonstrated to induce hypertension. The present study was designed to explore whether the renin-angiotensin system (RAS) plays a role in this process and the possible mechanisms involved in chronic-foot-shock-induced hypertension. Male Sprague-Dawley rats were subjected to a two-week foot shock with or without an angiotensin II (Ang II) type 1 receptor blocker (ARB, candesartan) or an angiotensin I converting enzyme inhibitor (ACEI, captopril). The expression of RAS components in the central nervous and circulatory systems was examined. Antioxidant levels in the plasma were monitored. Two-week foot shock significantly increased systolic blood pressure (SBP). Angiotensinogen, angiotensin I converting enzyme (ACE)-1, ACE-2, angiotensin type 1a and type 1b receptors, and vasopressin (VAP) mRNA expression in the cerebral cortex and hypothalamus were increased along with the concentration of renin and Ang II in the plasma; these changes were accompanied by decreased glutathione peroxidase activity and increased lipid peroxidation levels and plasma corticosterone concentrations. Both candesartan and captopril suppressed not only the increases in SBP but also the increases in VAP expression in the hypothalamus and RAS components in the central nervous system and the circulatory system. The decreases in antioxidant levels and the increases in lipid peroxidation and corticosterone levels were also partially reversed by candesartan or captopril treatment. Chronic foot shock increases expression of the main RAS components, which play an important role in the development of high blood pressure through increased VAP levels, oxidative stress levels and stress hormone levels. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. The renin-angiotensin system in conscious newborn sheep: metabolic clearance rate and activity.

    Science.gov (United States)

    Velaphi, Sithembiso C; Despain, Kevin; Roy, Timothy; Rosenfeld, Charles R

    2007-06-01

    The role of the renin-angiotensin system (RAS) in regulating newborn mean arterial blood pressure (MAP) and tissue blood flow remains unclear. Although postnatal MAP increases, vascular responsiveness to infused angiotensin II (ANG II) is unchanged, possibly reflecting increased metabolic clearance rate of ANG II (MCR(ANG II)). To address this, we examined MAP, heart rate, plasma ANG II and renin activity (PRA), and MCR(ANG II) in conscious postnatal sheep (n = 9, 5-35 d old) before and during continuous systemic ANG II infusions to measure MCR (ANG II). Postnatal MAP increased (p < 0.02), whereas plasma ANG II decreased from 942 +/- 230 (SEM) to 471 +/- 152 and 240 +/- 70 pg/mL at <10 d, 10-20 d, and 21-35 d postnatally (p = 0.05), respectively. Despite high plasma ANG II, PRA remained elevated, averaging 6.70 +/- 1.1 ng/mL.h throughout the postnatal period, but decreased 35% (p = 0.01) during ANG II infusions. MCR(ANG II) decreased approximately sixfold after birth and averaged 115 mL/min.kg during the first month. Circulating ANG II is markedly increased after birth, reflecting placental removal, high fetal MCR(ANG II), and enhanced RAS activity. Although circulating ANG II decreases as MAP increases, MCR(ANG II) is unchanged, suggesting decreased ANG II production. Persistent vascular smooth muscle (VSM) AT2 receptor subtype (AT2R) expression after birth may modify the hypertensive effects of ANG II postnatally.

  6. Brain renin-angiotensin system: fetal epigenetic programming by maternal protein restriction during pregnancy.

    Science.gov (United States)

    Goyal, Ravi; Goyal, Dipali; Leitzke, Arthur; Gheorghe, Ciprian P; Longo, Lawrence D

    2010-03-01

    Maternal protein malnutrition during pregnancy can lead to significant alterations in the systemic renin-angiotensin system (RAS) in the fetus. All components of the RAS are present in brain and may be altered in many disease states. Importantly, these disorders are reported to be of higher incidence in prenatally malnourished individuals. In the current study, we tested the hypothesis that antenatal maternal low protein diet (MLPD) leads to epigenetic changes and alterations in gene expression of brain RAS of the mouse fetus. Mice dams were given control and 50% MLPD during second half of the gestation. We analyzed messenger RNA (mRNA), microRNA (miRNA), promoter DNA methylation, and protein expression of various RAS genes in the fetal offspring. As a consequence of 50% MLPD, fetal brains showed increased mRNA expression of angiotensinogen and angiotensin converting enzyme-1 (ACE-1), with a decrease in mRNA levels of angiotensin II type-2 (AT2) receptors. In contrast, while angiotensinogen protein expression was unaltered, the protein levels of ACE-1 and AT2 receptor genes were significantly reduced in the fetal brain from the MLPD dams. Our results also demonstrated hypomethylation of the CpG islands in the promoter regions of ACE-1 gene, and upregulation of the miRNAs, mmu-mir-27a and 27b, which regulate ACE-1 mRNA translation. Furthermore, our study showed reduced expression of the miRNA mmu-mir-330, which putatively regulates AT2 translation. For the developing fetal brain RAS, MLPD leads to significant alterations in the mRNA and protein expression, with changes in DNA methylation and miRNA, key regulators of hypertension in adults.

  7. Dual renin-angiotensin system blockade at optimal doses for proteinuria.

    Science.gov (United States)

    Laverman, Gozewijn D; Navis, Gerjan; Henning, Robert H; de Jong, Paul E; de Zeeuw, Dick

    2002-09-01

    The antiproteinuric effect of combining the angiotensin-converting enzyme (ACE) inhibitor lisinopril and the angiotensin II (Ang II) antagonist losartan was compared to that of the optimal antiproteinuric doses of monotherapy. To this purpose, lisinopril and losartan were studied in 9 nondiabetic renal patients with median proteinuria 4.5 g/day (95% CI, 3.5, 6.4), creatinine clearance of 80 mL/min (95% CI, 66, 96), and mean arterial pressure (MAP) of 102 mm Hg (95% CI, 93, 112). First, in two protocols with six-week treatment periods per dose, the optimal antiproteinuric dose of each drug was established in each patient. Losartan and lisinopril were used in randomized order, each preceded by a baseline period without medication. The doses of losartan (mg/day) were 50, 100, 150, and again 50. The lisinopril doses were 10, 20, 40, and again 10. After the second protocol, patients were treated with a combination, using the optimal antiproteinuric doses established for the individual drugs. The antiproteinuric response by losartan was optimal at 100 mg (-46%; 95% CI, -60, -24%), being larger than at the 50 mg dose (-27%; 95% CI, -42, -4%, P 150 mg dose (-46%; 95% CI, -58; -20%). Proteinuria decreased further at each up-titration step of lisinopril to -75% (95% CI, -85, -43%) at the 40 mg dose. Combination therapy reduced proteinuria more effectively (-85%; 95% CI, -96, -58) than monotherapy with losartan, and to a lesser extent than with lisinopril. Optimal blood pressure responses were obtained at similar doses. Dose-titration with a renin-angiotensin system blocker, followed by add-on therapy is highly effective in order to reduce proteinuria. The safety of this regimen needs to be addressed in future studies.

  8. Renin-angiotensin system blockade therapy after transcatheter aortic valve implantation.

    Science.gov (United States)

    Ochiai, Tomoki; Saito, Shigeru; Yamanaka, Futoshi; Shishido, Koki; Tanaka, Yutaka; Yamabe, Tsuyoshi; Shirai, Shinichi; Tada, Norio; Araki, Motoharu; Naganuma, Toru; Watanabe, Yusuke; Yamamoto, Masanori; Hayashida, Kentaro

    2018-04-01

    The persistence of left ventricular (LV) hypertrophy is associated with poor clinical outcomes after transcatheter aortic valve implantation (TAVI) for aortic stenosis. However, the optimal medical therapy after TAVI remains unknown. We investigated the effect of renin-angiotensin system (RAS) blockade therapy on LV hypertrophy and mortality in patients undergoing TAVI. Between October 2013 and April 2016, 1215 patients undergoing TAVI were prospectively enrolled in the Optimized CathEter vAlvular iNtervention (OCEAN)-TAVI registry. This cohort was stratified according to the postoperative usage of RAS blockade therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). Patients with at least two prescriptions dispensed 180 days apart after TAVI and at least a 6-month follow-up constituted the RAS blockade group (n=371), while those not prescribed any ACE inhibitors or ARBs after TAVI were included in the no RAS blockade group (n=189). At 6 months postoperatively, the RAS blockade group had significantly greater LV mass index regression than the no RAS blockade group (-9±24% vs -2±25%, p=0.024). Kaplan-Meier analysis revealed a significantly lower cumulative 2-year mortality in the RAS blockade than that in the no RAS blockade group (7.5% vs 12.5%; log-rank test, p=0.031). After adjusting for confounding factors, RAS blockade therapy was associated with significantly lower all-cause mortality (HR, 0.45; 95% CI 0.22 to 0.91; p=0.025). Postoperative RAS blockade therapy is associated with greater LV mass index regression and reduced all-cause mortality. These data need to be confirmed by a prospective randomised controlled outcome trial. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Chronic Renin-Angiotensin System (RAS) Blockade May Not Induce Hypotension During Anaesthesia for Bariatric Surgery.

    Science.gov (United States)

    Salvetti, Guido; Di Salvo, Claudio; Ceccarini, Giovanni; Abramo, Antonio; Fierabracci, Paola; Magno, Silvia; Piaggi, Paolo; Vitti, Paolo; Santini, Ferruccio

    2016-06-01

    The use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) for the treatment of hypertensive obese patients is steadily increasing. Some studies have reported that the use of these drugs was associated with an increased risk of hypotensive episodes, during general anaesthesia. The number of bariatric procedures is also increasing worldwide, but there is a lack of studies investigating the hypotensive effect of renin-angiotensin system (RAS) blockers in severely obese patients during general anaesthesia for bariatric surgery. The aim of this pilot study was to evaluate hemodynamic changes induced by general anaesthesia in obese patients chronically treated with ACE-I or ARB compared to a control group not treated with antihypertensive therapy. Fourteen obese subjects (mean body mass index (BMI) 47.5 kg/m(2)) treated with ACE-I or ARB and twelve obese (mean BMI 45.7 kg/m2) controls not treated with antihypertensive therapy underwent general anaesthesia to perform laparoscopic bariatric surgery. Systolic blood pressure, diastolic blood pressure, and heart rate were monitored continuously and registered at different time points: T0 before induction, then at 2, 5, 7, 10, 15, 20, 30, 60, 90, 120, and 150 min after induction, and the last time point taken following recovery from anaesthesia. A progressive reduction of both systolic and diastolic blood pressure values was observed without significant differences between the two groups. A similar trend of heart rate values was observed. In conclusion, our pilot study suggests that RAS blockers may be continued during the perioperative period in patients undergoing bariatric surgery, without increasing the risk of hypotensive episodes.

  10. Renin-angiotensin system at the crossroad of hypertension and hypercholesterolemia.

    Science.gov (United States)

    Borghi, C; Urso, R; Cicero, A F

    2017-02-01

    The aim of this study is to discuss the reliable scientific evidence of an interactive link between hypertension and hypercholesterolemia considering the metabolic pathways and the pathogenetic mechanisms connecting the two risk factors. Hypertension and hypercholesterolemia are highly prevalent in the general population and their coexistence in the same subjects additively increases the risk of cardiovascular disease. Probably, hypercholesterolemia is also a risk factor for the development of hypertension. On the other side, it is also possible that lipid-lowering treatment could improve blood pressure control. Although the mechanisms of interaction between these two risk factors have not been completely elucidated thus far, there is rapidly growing evidence that the involvement of the renin-angiotensin system (RAS) can be considered as the common link between hypertension and hypercholesterolemia. In particular, hypercholesterolemia seems to promote the upregulation of type 1 angiotensin II (AT1) receptor genes because of an increase in the stability of mRNA followed by structural overexpression of vascular AT1 receptors for angiotensin II. The treatment of both risk factors greatly improves individual risk profile, especially when statins and RAS blockers are used together. Hypertension and hypercholesterolemia are highly coprevalent and strongly related from a pathophysiological point of view. The RAS could be the main mediator of this link. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  11. The placental renin-angiotensin system and oxidative stress in pre-eclampsia.

    Science.gov (United States)

    Mistry, H D; Kurlak, L O; Broughton Pipkin, F

    2013-02-01

    There is an inverse correlation between human birthweight and umbilical venous angiotensin II (AngII) concentrations. Oxidative stress and increased pro-renin receptor (PRR) both enhance the cleavage of angiotensin I from angiotensinogen (AGT). Pre-eclampsia, a hypertensive disorder of pregnancy, manifests as high blood pressure and proteinuria, and is a state of increased oxidative stress. Pre-eclampsia will be associated with increased placental expression of components of the renin-angiotensin system, which could result in reduced infant birthweight. Biopsies were taken 1 cm from the placental edge from 27 normotensive controls and 23 pre-eclamptic White European women. Immunohistochemistry was performed for AGT, PRR, glutathione peroxidase 3 (GPx3) and the AT1R and AT2R AngII receptors. Protein expression was semi-quantitatively assessed (H-score). AT1R expression was significantly increased in pre-eclamptic placentae, and negatively correlated with birthweight (r = -0.529, P = 0.009). AT1R expression was also negatively correlated with GPx3 expression overall (r = -0.647; P = 0.005). AT2R expression positively correlated with AGT (r = 0.615, P = 0.002) in the pre-eclamptic placentae only. The raised AT1R expression in pre-eclampsia, together with inadequate antioxidant protection, possibly through lower GPx activity, might enhance the vasoconstrictor effect of locally-generated AngII, contributing to the restricted fetal growth characteristic of pre-eclampsia. Conversely, the AT2R:AGT association within the pre-eclamptic placenta may provide a compensatory mechanism. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. A Local Inflammatory Renin-Angiotensin System Drives Sensory Axon Sprouting in Provoked Vestibulodynia.

    Science.gov (United States)

    Liao, Zhaohui; Chakrabarty, Anuradha; Mu, Ying; Bhattacherjee, Aritra; Goestch, Martha; Leclair, Catherine M; Smith, Peter G

    2017-05-01

    Vestibulodynia is a form of provoked vulvodynia characterized by profound tenderness, hyperinnervation, and frequently inflammation within well-defined areas of the human vestibule. Previous experiments in animal models show that inflammatory hypersensitivity and hyperinnervation occur in concert with establishment of a local renin-angiotensin system (RAS). Moreover, mechanical hypersensitivity and sensory axon sprouting are prevented by blocking effects of angiotensin II on angiotensin II receptor type 2 (AT2) receptors. This case-control study assessed whether a RAS contributes to hyperinnervation observed in human vestibulodynia. Vestibular biopsies from asymptomatic controls or patients' nontender areas showed moderate innervation and small numbers of inflammatory cells. In women with vestibulodynia, tender areas contained increased numbers of mechanoreceptive nociceptor axons, T-cells, macrophages, and B-cells, whereas mast cells were unchanged. RAS proteins were increased because of greater numbers of T cells and B cells expressing angiotensinogen, and increased renin-expressing T cells and macrophages. Chymase, which converts angiotensin I to angiotensin II, was present in constant numbers of mast cells. To determine if tender vestibular tissue generates angiotensin II that promotes axon sprouting, we conditioned culture medium with vestibular tissue. Rat sensory neurons cultured in control-conditioned medium showed normal axon outgrowth, whereas those in tender tissue-conditioned medium showed enhanced sprouting that was prevented by adding an AT2 antagonist or angiotensin II neutralizing antibody. Hypersensitivity in provoked vestibulodynia is therefore characterized by abnormal mechanonociceptor axon proliferation, which is attributable to inflammatory cell-derived angiotensin II (or a closely related peptide) acting on neuronal AT2 receptors. Accordingly, reducing inflammation or blocking AT2 represent rational strategies to mitigate this common pain

  13. Targeting the renin-angiotensin system as novel therapeutic strategy for pulmonary diseases.

    Science.gov (United States)

    Tan, Wan Shun Daniel; Liao, Wupeng; Zhou, Shuo; Mei, Dan; Wong, Wai-Shiu Fred

    2017-12-27

    The renin-angiotensin system (RAS) plays a major role in regulating electrolyte balance and blood pressure. RAS has also been implicated in the regulation of inflammation, proliferation and fibrosis in pulmonary diseases such as asthma, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Current therapeutics suffer from some drawbacks like steroid resistance, limited efficacies and side effects. Novel intervention is definitely needed to offer optimal therapeutic strategy and clinical outcome. This review compiles and analyses recent investigations targeting RAS for the treatment of inflammatory lung diseases. Inhibition of the upstream angiotensin (Ang) I/Ang II/angiotensin receptor type 1 (AT 1 R) pathway and activation of the downstream angiotensin-converting enzyme 2 (ACE2)/Ang (1-7)/Mas receptor pathway are two feasible strategies demonstrating efficacies in various pulmonary disease models. More recent studies favor the development of targeting the downstream ACE2/Ang (1-7)/Mas receptor pathway, in which diminazene aceturate, an ACE2 activator, GSK2586881, a recombinant ACE2, and AV0991, a Mas receptor agonist, showed much potential for further development. As the pathogenesis of pulmonary diseases is so complex that RAS modulation may be used alone or in combination with existing drugs like corticosteroids, pirfenidone/nintedanib or endothelin receptor antagonists for different pulmonary diseases. Personalized medicine through genetic screening and phenotyping for angiotensinogen or ACE would aid treatment especially for non-responsive patients. This review serves to provide an update on the latest development in the field of RAS targeting for pulmonary diseases, and offer some insights into future direction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Preoperative renin-angiotensin system inhibitors protect renal function in aging patients undergoing cardiac surgery.

    Science.gov (United States)

    Barodka, Viachaslau; Silvestry, Scott; Zhao, Ning; Jiao, Xiangyin; Whellan, David J; Diehl, James; Sun, Jian-Zhong

    2011-05-15

    Renal failure (RF) represents a major postoperative complication for elderly patients undergoing cardiac surgery. This observational cohort study examines effects of preoperative use of renin-angiotensin system (RAS) inhibitors on postoperative renal failure in aging patients undergoing cardiac surgery. We retrospectively analyzed a cohort of 1287 patients who underwent cardiac surgery at this institution (2003-2007). The patients included were ≥65 years old, scheduled for elective cardiac surgery, and without preexisting RF (defined by the criteria of the Society of Thoracic Surgeons as described in Method). Of all patients evaluated, 346 patients met the inclusion criteria and were divided into two groups: using (n = 122) or not using (n = 224) preoperative RAS inhibitors. A comparison of the two groups showed no significant differences in baseline parameters, including creatinine clearance, body mass index, history of diabetes and smoking, preoperative medicines (except that more patients with RAS inhibitors had a history of hypertension or congestive heart failure, fewer RAS inhibitor patients had chronic lung disease), in intraoperative perfusion and aortic cross-clamp time, and in postoperative complications and 30-d mortality. Multivariate logistic regression analysis demonstrated, however, that preoperative RAS inhibitors significantly and independently reduced the incidence of postoperative RF in the patients undergoing cardiac surgery compared with those not taking RAS inhibitors: 1.6% versus 7.6%, yielding an odds ratio of 0.19 (95 % CI 0.04-0.84, P = 0.029). Preoperative RAS inhibitors may have significant renoprotective effects for aging patients undergoing elective cardiac surgery. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Modulation of the cardiac sodium/bicarbonate cotransporter by the renin angiotensin aldosterone system: pathophysiological consequences.

    Science.gov (United States)

    De Giusti, Verónica C; Ciancio, María C; Orlowski, Alejandro; Aiello, Ernesto A

    2013-01-01

    The sodium/bicarbonate cotransporter (NBC) is one of the major alkalinizing mechanisms in the cardiomyocytes. It has been demonstrated the existence of at least two functional isoforms, one that promotes the co-influx of 1 molecule of Na(+) per 1 molecule of HCO(-) 3 (electroneutral isoform; NBCn1) and the other one that generates the co-influx of 1 molecule of Na(+) per 2 molecules of HCO(-) 3 (electrogenic isoform; NBCe1). Both isoforms are important to maintain intracellular pH (pH i ) and sodium concentration ([Na(+)] i ). In addition, NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD). The renin-angiotensin-aldosterone system (RAAS) is implicated in the modulation of almost all physiological cardiac functions and is also involved in the development and progression of cardiac diseases. It was reported that angiotensin II (Ang II) exhibits an opposite effect on NBC isoforms: it activates NBCn1 and inhibits NBCe1. The activation of NBCn1 leads to an increase in pH i and [Na(+)] i , which indirectly, due to the stimulation of reverse mode of the Na(+)/Ca(2+) exchanger (NCX), conduces to an increase in the intracellular Ca(2+) concentration. On the other hand, the inhibition of NBCe1 generates an APD prolongation, potentially representing a risk of arrhythmias. In the last years, the potentially altered NBC function in pathological scenarios, as cardiac hypertrophy and ischemia-reperfusion, has raised increasing interest among investigators. This review attempts to draw the attention on the relevant regulation of NBC activity by RAAS, since it modulates pH i and [Na(+)] i , which are involved in the development of cardiac hypertrophy, the damage produced by ischemia-reperfusion and the generation of arrhythmic events, suggesting a potential role of NBC in cardiac diseases.

  16. Dysregulation of the renin-angiotensin system during lung ischemia-reperfusion injury.

    Science.gov (United States)

    Kehoe, K; Gielis, J F; Vliegen, G; Van Elzen, R; Verkerk, R; Driessens, E; Domen, A; Lambeir, A M; Maes, L; Cos, P; De Meester, I; Van Schil, P E Y

    2016-08-01

    Aim/Purpose of the Study: Activation of the renin-angiotensin system leading to increased angiotensin-(1-7) (Ang-(1-7)) and decreased angiotensin 2 (Ang 2) levels may be a new therapeutic approach to reduce acute lung injury. Prolylcarboxypeptidase (PRCP) and prolyloligopeptidase (PREP) are capable of hydrolyzing Ang 2 into Ang-(1-7). However, their relation with circulating Ang 2 levels after lung ischemia-reperfusion injury (LIRI) has never been explored. This study determines whether the activity and expression of PRCP and PREP in plasma and lung tissue is related to circulating Ang 2 levels in a murine model of LIRI. LIRI in Swiss mice (6 animals per group) was induced by temporary left lung hilar clamping (1 h) followed by 0, 1 or 24 h of reperfusion. Animals in the sham group received thoracotomy only. PRCP activity was measured via RP-HPLC, PREP activity using a fluorogenic substrate and plasma Ang 2 levels via ELISA. Western blotting was used to determine the PRCP and PREP protein expression profiles in left lung tissue. Plasma Ang 2 levels significantly rise after lung ischemia and remain increased after 1 h and 24 h of reperfusion compared to the sham group. While a significant decrease in plasma PREP activity was found after 24 h of reperfusion, a transient increase in plasma PRCP activity was observed after ischemia. However, no correlation with plasma Ang 2 levels could be demonstrated. The activity profiles of PRCP and PREP and the protein expression of PRCP in the lung tissues remained unchanged after LIRI. LIRI causes a dysregulation of circulating Ang 2 levels and plasma PREP activity, although no direct link between both phenomena could be shown. The activity profile of pulmonary PRCP and PREP was not significantly changed after LIRI, which implies a minor role for local PRCP and PREP in the ischemic lung itself.

  17. [Elevated serum aldosterone levels in dialysis patients: Are we underusing renin-angiotensin-aldosterone system blockers?

    Science.gov (United States)

    Fernández-Reyes, M J; Velasco, S; Gutierrez, C; Gonzalez Villalba, M J; Heras, M; Molina, A; Callejas, R; Rodríguez, A; Calle, L; Lopes, V

    Serum aldosteronelevels (SA) are a marker of cardiovascular (CV) risk in the general population. To analyze SA levels in dialysis patients and its relationship with characteristics of dialysis; comorbidity; blood pressure and the use of blocking renin-angiotensin-aldosterone system agents (BSRAA). We determined SA in 102 patients: 81 on hemodialysis (HD) and 21 on peritoneal dialysis. Mean age 71.4±12 years; 54.9% male; 29.4% diabetics. Mean time on dialysis 59.3±67 months. In 44 HD patients plasma renin activity (PRA) was measured. Mean SA was 72.6±114.9ng/dl (normal range 1.17-23.6ng/dl). A total of 57.8% of patients had above normal levels which were not related to dialysis characteristics or comorbidity. Only 21% of patients with heart failure and 19.2% with ischemic heart disease used BSRAA. A number of 25 patients treated with BSRAA had significantly lower levels of SA. There was an inverse correlation between AS and systolic blood pressure (SBP), and direct with PRA. The logistic regression analysis conducted to find SA levels above the median associated factors showed that SBP was the only independent risk variable in the overall population (OR 0.97; P=.022); in the 44 patients in whom PRA was determined this was the only independent risk factor (OR 2.24; P=.012). A high percentage of dialysis patients have elevated levels of SA that are associated to diminished SBP and activated PRA and not to dialysis characteristics. In patients with a history of heart disease we underuse BSRAA. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Renin-angiotensin-aldosterone system in bodybuilders using supraphysiological doses of anabolic-androgenic steroids

    Directory of Open Access Journals (Sweden)

    K Chrostowski

    2011-03-01

    Full Text Available This study was carried out in 40 bodybuilders voluntarily taking supraphysiological doses of anabolic-androgenic steroids (AAS. Echocardiographic examination of the heart and blood analysis were performed, and concentration of AAS in urine was examined. The presence, or absence, of AAS in urine had no influence on the echocardiographic parameters of the heart, body mass, body mass index (BMI and aldosterone level in blood plasma. It seems, therefore, that the presence of AAS in urine may confirm heart hypertrophy and overuse of AAS, while the absence of AAS in urine does not exclude the cardiological changes occurring as a result of taking the drugs. Metabolites detected in urine showed that the intake of 17α-alkyl testosterone derivatives caused higher values of left ventricular mass and BMI. However, the level of HDL cholesterol was lower in bodybuilders using only 19-nor-testosterone. Elevated level of plasma aldosterone did not differ between the two groups. As could be expected, the highest level of AAS in urine was detected in bodybuilders currently self-administering the anabolic-androgenic steroids (on cycle. The level of AAS in the urine decreased after stopping taking the drugs (off cycle. Refraining from AAS abuse for a period of 1-2 years was associated with a significant decrease in aldosterone level in the plasma. The positive correlations found between the blood plasma aldosterone, left ventricular mass and BMI lead to the conclusion that large doses of AAS taken by bodybuilders would cause extra activation of the renin-angiotensin-aldosterone system.

  19. Different expression of renin-angiotensin system components in hearts of normotensive and hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Jurkovičová, D.; Dobešová, Zdenka; Kuneš, Jaroslav; Križanová, O.

    2001-01-01

    Roč. 50, č. 1 (2001), s. 35-42 ISSN 0862-8408 R&D Projects: GA AV ČR IAA7011805 Grant - others:VEGA(SK) 2/7158(OK) Institutional research plan: CEZ:AV0Z5011922 Keywords : renin- angiotensin systém * heart * hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.027, year: 2001

  20. Regression of cardiac hypertrophy in the SHR by combined renin-angiotensin system blockade and dietary sodium restriction

    Directory of Open Access Journals (Sweden)

    Emad Abro

    2001-03-01

    Full Text Available Altered operation of the renin-angiotensin-aldosterone system (RAAS and dietary sodium intake have been identified as independent risk factors for cardiac hypertrophy. The way in which sodium intake and the operation of the renin-angiotensin-aldosterone system interact in the pathogenesis of cardiac hypertrophy is poorly understood. The aims of this study were to investigate the cardiac effects of the renin-angiotensin system (RAS blockade in the spontaneously hypertensive rat (SHR, using co-treatment with an angiotensin II receptor blocker (ARB and an angiotensin-converting enzyme (ACE inhibitor with different sodium intakes. Our experiments with SHR show that, at high levels of sodium intake (4.0%, aggressive RAS blockade treatment with candesartan (3 mg/kg and perindopril (6 mg/kg does not result in regression of cardiac hypertrophy. In contrast, RAS blockade coupled with reduced sodium diet (0.2% significantly regresses cardiac hypertrophy, impairs animal growth and is associated with elevated plasma renin and dramatically suppressed plasma angiotensinogen levels. Histological analyses indicate that the differential effect of reduced sodium on heart growth during RAS blockade is not associated with any change in myocardial interstitial collagen, but reflects modification of cellular geometry. Dimensional measurements of enzymatically-isolated ventricular myocytes show that, in the RAS blocked, reduced sodium group, myocyte length and width were decreased by about 16—19% compared with myocytes from the high sodium treatment group. Our findings highlight the importance of `titrating' sodium intake with combined RAS blockade in the clinical setting to optimise therapeutic benefit.

  1. Low birth weight activates the renin?angiotensin system, but limits cardiac angiogenesis in early postnatal life

    OpenAIRE

    Wang, Kimberley C W; Brooks, Doug A; Summers-Pearce, Brooke; Bobrovskaya, Larisa; Tosh, Darran N; Duffield, Jaime A; Botting, Kimberley J; Zhang, Song; Caroline McMillen, I; Morrison, Janna L

    2015-01-01

    Low birth weight (LBW) is associated with increased risk of adult cardiovascular disease and this association may be partly a consequence of early programming of the renin?angiotensin system (RAS). We investigated the effects of LBW on expression of molecules in the RAS and cardiac tissue remodeling. Left ventricular samples were collected from the hearts of 21?days old lambs that were born average birth weight (ABW) and LBW. Cardiac mRNA expression was quantified using real-time RT-PCR and p...

  2. Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin-angiotensin system inhibitors in the community increases the risk of acute kidney injury.

    Science.gov (United States)

    Dreischulte, Tobias; Morales, Daniel R; Bell, Samira; Guthrie, Bruce

    2015-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diuretics alone were not. However, earlier studies relied on hospital coding to define AKI, which may underestimate true risk. This nested case-control study characterized the risk of community-acquired AKI associated with NSAID use among 78,379 users of renin-angiotensin system inhibitors and/or diuretics, where AKI was defined as a 50% or greater increase in creatinine from baseline. The AKI incidence was 68/10,000 person-years. The relative increase in AKI risk was similar for NSAID use in both triple (adjusted rate ratio 1.64 (95% CI 1.25-2.14)) and dual combinations with either renin-angiotensin system inhibitors (1.60 (1.18-2.17)) or diuretics (1.64 (1.17-2.29)). However, the absolute increase in AKI risk was higher for NSAIDs used in triple versus dual combinations with renin-angiotensin system inhibitors or diuretics alone (numbers needed to harm for 1 year treatment with NSAID of 158 vs. over 300). AKI risk was highest among users of loop diuretic/aldosterone antagonist combinations, in those over 75 years of age, and in those with renal impairment. Thus, the nephrotoxic potential of both dual and triple combinations of NSAIDs with renin-angiotensin system inhibitors and/or diuretics yields a higher incidence of AKI than previously thought.

  3. Circadian Differences in the Contribution of the Brain Renin-Angiotensin System in Genetically Hypertensive Mice

    Directory of Open Access Journals (Sweden)

    Kristy L. Jackson

    2018-03-01

    Full Text Available Objective: Genetically hypertensive BPH/2J mice are recognized as a neurogenic model of hypertension, primarily based on sympathetic overactivity and greater neuronal activity in cardiovascular regulatory brain regions. Greater activity of the central renin angiotensin system (RAS and reactive oxygen species (ROS reportedly contribute to other models of hypertension. Importantly the peripheral RAS contributes to the hypertension in BPH/2J mice, predominantly during the dark period of the 24 h light cycle. The aim of the present study was to determine whether central AT1 receptor stimulation and the associated ROS signaling contribute to hypertension in BPH/2J mice in a circadian dependent manner.Methods: Blood pressure (BP was measured in BPH/2J and normotensive BPN/3J mice (n = 7–8 via pre-implanted telemetry devices. Acute intracerebroventricular (ICV microinjections of AT1 receptor antagonist, candesartan, and the superoxide dismutase (SOD mimetic, tempol, were administered during the dark and light period of the 24 h light cycle via a pre-implanted ICV guide cannula. In separate mice, the BP effect of ICV infusion of the AT1 receptor antagonist losartan for 7 days was compared with subcutaneous infusion to determine the contribution of the central RAS to hypertension in BPH/2J mice.Results: Candesartan administered ICV during the dark period induced depressor responses which were 40% smaller in BPH/2J than BPN/3J mice (Pstrain < 0.05, suggesting AT1 receptor stimulation may contribute less to BP maintenance in BPH/2J mice. During the light period candesartan had minimal effect on BP in either strain. ICV tempol had comparable effects on BP between strains during the light and dark period (Pstrain > 0.08, suggesting ROS signaling is also not contributing to the hypertension in BPH/2J mice. Chronic ICV administration of losartan (22 nmol/h had minimal effect on BPN/3J mice. By contrast in BPH/2J mice, both ICV and subcutaneously administered

  4. The renin-angiotensin system and vascular function. The role of angiotensin II, angiotensin-converting enzyme, and alternative conversion of angiotensin I

    NARCIS (Netherlands)

    Roks, A.; Buikema, H.; Pinto, Y. M.; van Gilst, W. H.

    1997-01-01

    The renin-angiotensin system has been implicated in vascular function and disease. Angiotensin-converting enzyme and angiotensin II are believed to be the most important components. However, alternative factors, such as angiotensin-I/II-(1-7) and chymase, have also been shown to be of significance

  5. Multilocus analyses of renin-angiotensin-aldosterone system gene variants on blood pressure at rest and during behavioral stress in young normotensive subjects

    NARCIS (Netherlands)

    Ge, Dongliang; Zhu, Haidong; Huang, Ying; Treiber, Frank A.; Harshfield, Gregory A.; Snieder, Harold; Dong, Yanbin

    The renin-angiotensin-aldosterone system (RAAS) is a proteolytic cascade that regulates and maintains blood pressure (BP). This study aimed to explore the interactive and integrative effects of multiple RAAS polymorphisms on BP at rest and during behavioral stress in a normotensive population. A

  6. Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial

    NARCIS (Netherlands)

    de Vries, Laura V.; Dobrowolski, Linn C.; van den Bosch, Jacqueline J. O. N.; Riphagen, Ineke J.; Krediet, C. T. Paul; Bemelman, Frederike J.; Bakker, Stephan J. L.; Navis, Gerjan

    2016-01-01

    In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore

  7. Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade : A Randomized Clinical Trial

    NARCIS (Netherlands)

    de Vries, Laura V; Dobrowolski, Linn C; van den Bosch, Jacqueline J O N; Riphagen, Ineke J; Krediet, C T Paul; Bemelman, Frederike J; Bakker, Stephan J L; Navis, Gerjan

    BACKGROUND: In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown.

  8. Differences in cortical and pituitary activity in response to hypoglycaemia and cognitive testing in healthy men with different basal activity of the renin-angiotensin system

    DEFF Research Database (Denmark)

    Bie-Olsen, Lise G; Pedersen-Bjergaard, Ulrik; Kjaer, Troels W

    2010-01-01

    INTRODUCTION: High renin-angiotensin system (RAS) activity has been associated with a high risk of severe hypoglycaemia in patients with type 1 diabetes and with cognitive deterioration during experimental hypoglycaemia in healthy subjects. The aim of this study was to describe possible differenc...

  9. Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels

    NARCIS (Netherlands)

    Asselbergs, Folkert W.; Williams, Scott M.; Hebert, Patricia R.; Coffey, Christopher S.; Hillege, Hans L.; Navis, Gerjan; Vaughan, Douglas E.; van Gilst, Wiek H.; Moore, Jason H.

    Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) directly influence thrombus formation and degradation and thereby risk for arterial thrombosis. Activation of the renin-angiotensin system has been linked to the production of PAI-1 expression via the angiotensin II

  10. Effects of warming yang and invigorating qi prescription on renin-angiotensin-aldosterone system in rats with heart failure after myocardial infarction

    Directory of Open Access Journals (Sweden)

    Lihua HAN

    Full Text Available Abstract This study investigated the effects of warming yang and invigorating qi prescription on renin-angiotensin-aldosterone system (RAAS in rats with heart failure after myocardial infarction. 126 rats were randomly divided into model group, sham operation, warming yang, invigorating qi, warming yang+invigorating qi, digoxin and captopril group for respective treatment. After intervention for 6, 8 and 10 weeks, the left ventricular ejection fraction (LVEF was calculated, and the plasma renin, angiotensin II and aldosterone levels were measured. Results showed that, after 6, 8 and 10 weeks, LVEF in warming yang, invigorating qi, warming yang+invigorating qi and captopril group was significantly higher than model group (P < 0.05, and the plasma renin, angiotensin II and aldosterone levels in warming yang, invigorating qi, warming yang+invigorating qi and captopril groups were significantly lower than model group (P < 0.05. Renin angiotensin II and aldosterone levels in invigorating qi, warming yang+invigorating qi and captopril groups after 10 weeks was significantly lower than after 6 weeks (P < 0.05; aldosterone level in captopril groups after 10 weeks was significantly lower than after 6 weeks (P < 0.05. Warming yang and invigorating qi prescription can improve LVEF in rats with heart failure after myocardial infarction, which may be related with the inhibition of RAAS activation.

  11. Pooled Analysis of Multiple Crossover Trials To Optimize Individual Therapy Response to Renin-Angiotensin-Aldosterone System Intervention

    DEFF Research Database (Denmark)

    Petrykiv, Sergei I.; Laverman, Gozewijn Dirk; Persson, Frederik

    2017-01-01

    BACKGROUND AND OBJECTIVES: In the treatment of CKD, individual patients show a wide variation in their response to many drugs, including renin-angiotensin-aldosterone system inhibitors (RAASi). To investigate whether therapy resistance to RAASi can be overcome by uptitrating the dose of drug......, changing the mode of intervention (with drugs from similar or different classes), or lowering dietary sodium intake, we meta-analyzed individual responses to different modes of interventions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Randomized crossover trials were analyzed to assess correlation...... of individual responses to RAASi and nonsteroidal anti-inflammatory drugs (NSAIDs; n=395 patients). Included studies compared the antialbuminuric effect of uptitrating the dose of RAASi (n=10 studies) and NSAIDs (n=1), changing within the same class of RAASi (e.g., angiotensin-converting enzyme inhibition...

  12. [Changes in the renin-angiotensin-aldosterone system and water-salt exchange in mining workers in coal mines].

    Science.gov (United States)

    Rebrov, B A

    1996-01-01

    Blood and urine content of electrolytes and creatinine was determined in 76 essentially healthy miners before and after work shift, as was activity of plasma renin, blood plasma level of aldosterone and its urinary excretion, with the aid of radioimmunoassay. The greatest activity of the renin-angiotensine-aldosterone system (RAAS) occurred in those individuals engaged in hard physical labour under most harsh conditions of underground workings, this being recordable not only is response to the load but also from the very start. Controls and miners doing jobs of medium-level strenuousness demonstrated changes in the correlations between RAAS and water-salt balance after the work shift as compared with those before the work shift, while in those miners engaged in hard work correlations RAAS-water-salt exchange remained practically the same throughout the study.

  13. A high sodium intake reduces antiproteinuric response to renin-angiotensin-aldosterone system blockade in kidney transplant recipients.

    Science.gov (United States)

    Monfá, Elena; Rodrigo, Emilio; Belmar, Lara; Sango, Cristina; Moussa, Fozi; Ruiz San Millán, Juan Carlos; Piñera, Celestino; Fernández-Fresnedo, Gema; Arias, Manuel

    Post-transplant proteinuria is associated with lower graft and patient survival. Renin-angiotensin-aldosterone system blockers are used to reduce proteinuria and improve renal outcome. Although it is known that a high salt intake blunts the antiproteinuric effect of ACEI and ARB drugs in non-transplant patients, this effect has not been studied in kidney transplant recipients. To analyse the relationship between sodium intake and the antiproteinuric effect of ACEI/ARB drugs in kidney transplant recipients. We selected 103 kidney transplant recipients receiving ACEI/ARB drugs for more than 6 months due to proteinuria>1 g/day. Proteinuria was analysed at baseline and at 6 months after starting ACEI/ARB treatment. Salt intake was estimated by urinary sodium to creatinine ratio (uNa/Cr). Proteinuria fell to less than 1g/day in 46 patients (44.7%). High uNa/Cr was associated with a smaller proteinuria decrease (r=-0.251, P=.011). The percentage proteinuria reduction was significantly lower in patients in the highest uNa/Cr tertile [63.9% (IQR 47.1%), 60.1% (IQR 55.4%), 38.9% (IQR 85.5%), P=.047]. High uNa/Cr independently relates (OR 2.406 per 100 mEq/g, 95% CI: 1.008-5.745, P=.048) to an antiproteinuric response <50% after renin-angiotensin-aldosterone system blockade. A high salt intake results in a smaller proteinuria decrease in kidney transplant recipients with proteinuria treated with ACEI/ARB drugs. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Daily sesame oil supplementation attenuates local renin-angiotensin system via inhibiting MAPK activation and oxidative stress in cardiac hypertrophy.

    Science.gov (United States)

    Liu, Chuan-Teng; Liu, Ming-Yie

    2017-04-01

    The renin-angiotensin system (RAS) is involved in the development of left ventricular hypertrophy (LVH) by which increases cardiac morbidity and mortality. Activation of mitogen-activated protein kinases (MAPKs) and oxidative stress are important in RAS-mediated cardiac hypertrophy. Sesame oil, a potent antioxidant, attenuates hypertension-dependent LVH. We examined the protective role of sesame oil on RAS-mediated MAPK activation and oxidative stress in rats. We induced LVH using a hypertensive model by subcutaneously injecting deoxycorticosterone acetate (DOCA; 15 mg/ml/kg in mineral oil; twice weekly for 5 weeks) and supplementing with 1% sodium chloride drinking water (DOCA/salt) to uninephrectomized rats. Sesame oil was gavaged (0.5 or 1 ml/kg/day for 7 days) after 4 weeks of DOCA/salt treatment. Cardiac histopathology, RAS parameters, expression of MAPKs, reactive oxygen species and lipid peroxidation were assessed 24 h after the last dose of sesame oil. Sesame oil significantly decreased the size of cardiomyocytes and the levels of cardiac renin, angiotensin-converting enzyme and angiotensin II. In addition, sesame oil down-regulated the expression of angiotensin type 1 receptor, JNK and p38 MAPK and apoptosis signal regulating kinase 1, c-Fos and c-Jun in rats receiving DOCA/salt. Furthermore, the induction of nicotinamide adenine dinucleotide phosphate oxidase, superoxide anion and hydroxyl radical and lipid peroxidation by DOCA/salt were inhibited by sesame oil. Sesame oil modulates cardiac RAS to ameliorate LVH by inhibiting MAPK activation and lowering oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. KCNQ1 A340E impairs electrolyte homeostasis independently of the renin-angiotensin-aldosterone system in mice.

    Science.gov (United States)

    Pan, Q; Sang, Y; Sun, C; Li, G; Wang, Y

    2016-07-25

    KCNQ1 (KvLQT1) is the pore-forming a-subunit of the potassium channel. To uncover its role in electrolyte metabolism, we investigated the effects of KCNQ1 A340E, a loss-of-function mutant, on J343 mice. Compared with the normal controls (C57BL/6J mice) bearing the wild-type KCNQ1 gene, J343 mice bearing KCNQ1 A340E demonstrated a much higher 24-h intake of electrolytes (potassium, sodium, and chloride). However, they suffered from significant electrolyte loss through both the feces and urine during a period of 24 h. Unbalance in electrolyte metabolism disrupted the electrolyte homeostasis in the J343 mice, which was characterized by the comparatively lower level of serum potassium (J343 vs C57BL/6J: 12.06 ± 1.47 vs 14.44 ± 3.58 mM, P = 0.01) and higher levels of serum sodium (J343 vs C57BL/6J: 148.05 ± 4.47 vs 115.15 ± 17.25 mM, P = 4.20 x 10(-4)) and chloride (J343 vs C57BL/6J: 118.0 ± 4.47 vs 85.21 ± 11.90 mM, P = 2.47 x 10(-5)). Between the J343 and C57BL/6J mice, there was no statistically significant difference in KCNQ1 expression in the gastrointestinal tract and kidney. Normal concentrations of plasma renin, angiotensin I, and aldosterone were also detected in both lines of mice. KCNQ1, therefore, is suggested to play a central role in electrolyte metabolism. KCNQ1 A340E, with the loss-of-function phenotype, may dysregulate electrolyte homeostasis in mice independently of the activity of the renin-angiotensin-aldosterone system.

  16. Acute and chronic role of nitric oxide, renin-angiotensin system and sympathetic nervous system in the modulation of calcium sensitization in Wistar Rats

    Czech Academy of Sciences Publication Activity Database

    Brunová, Aneta; Bencze, Michal; Behuliak, Michal; Zicha, Josef

    2015-01-01

    Roč. 64, č. 4 (2015), s. 447-457 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP304/12/0259; GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : blood pressure * kalcium sensitization * Rho kinase * nitric oxide * renin-angiotensin system * sympathetic nervous system * fasudil Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.643, year: 2015

  17. Effects of aqueous extract of Hibiscus sabdariffa on the renin-angiotensin-aldosterone system of Nigerians with mild to moderate essential hypertension: A comparative study with lisinopril

    OpenAIRE

    Nwachukwu, Daniel Chukwu; Aneke, Eddy Ikemefuna; Obika, Leonard Fidelis; Nwachukwu, Nkiru Zuada

    2015-01-01

    Objectives: The present study investigated the effects of aqueous extract of Hibiscus sabdariffa (HS) on the three basic components of renin-angiotensin-aldosterone system: Plasma renin, serum angiotensin-converting enzyme (ACE), and plasma aldosterone (PA) in mild to moderate essential hypertensive Nigerians and compared with that of lisinopril, an ACE inhibitor. Materials and Methods: A double-blind controlled randomized clinical study was used. Seventy-eight newly diagnosed but untreate...

  18. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.

    Science.gov (United States)

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A; Castillo, Andrés E; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E; Kalergis, Alexis M

    2016-06-23

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage.

  19. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Natalia Muñoz-Durango

    2016-06-01

    Full Text Available Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage.

  20. Acute Total and Chronic Partial Sleep Deprivation: Effects on Neurobehavioral Functions, Waking EEG and Renin-Angiotensin System

    Science.gov (United States)

    Dijk, Derk-Jan

    1999-01-01

    protocol of the Quantitative EEG and Waking Neurobehavioral Function project. This will allow us to investigate two additional specific aims: 1) Test the hypothesis that chronic partial sleep deprivation during a 17 day bed rest experiment results in deterioration of neurobehavioral function during waking and increases in EEG power density in the theta frequencies, especially in frontal areas of the brain, as well as the nonREM- REM cycle dependent modulation of heart-rate variability. 2) Test the hypothesis that acute total sleep deprivation modifies the circadian rhythm of the renin-angiotensin system, changes the acute responsiveness of this system to posture beyond what a microgravity environment alone does and affects the nonREM-REM cycle dependent modulation of heart-rate variability.

  1. Palmitoylethanolamide treatment reduces blood pressure in spontaneously hypertensive rats: involvement of cytochrome p450-derived eicosanoids and renin angiotensin system.

    Directory of Open Access Journals (Sweden)

    Giuseppina Mattace Raso

    Full Text Available Palmitoylethanolamide (PEA, a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR. Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF, and renin angiotensin system (RAS modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the

  2. Renin-angiotensin system activity in vitamin D deficient, obese individuals with hypertension: An urban Indian study

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2011-01-01

    Full Text Available Background: Elevated renin-angiotensin-aldosterone system (RAAS activity is an important mechanism in the development of hypertension. Both obesity and 25-hydroxy vitamin D [25(OHD] deficiency have been associated with hypertension and augmented renin-angiotensin system (RAS activity. We tried to test the hypothesis that vitamin D deficiency and obesity are associated with increased RAS activity in Indian patients with hypertension. Materials and Methods: Fifty newly detected hypertensive patients were screened. Patients with secondary hypertension, chronic kidney disease, or coronary artery disease were excluded. Patients underwent measurement of vitamin D and plasma renin and plasma aldosterone concentrations. They were divided into three groups according to their baseline body mass index (BMI; normal <25 kg/m 2 , overweight 25-29.9 kg/m 2 and obese ≥30 kg/m 2 and 25(OHD levels (deficient <20 ng/ml, insufficient 20-29 ng/ml and optimal ≥30 ng/ml. Results: A total of 50 (male:female = 32:18 patients were included, with a mean age of 49.5 ± 7.8 years, mean BMI of 28.3 ± 3.4 kg/m 2 and a mean 25(OHD concentration of 18.5 ± 6.4 ng/ml. Mean systolic blood pressure (SBP was 162.4 ± 20.2 mm Hg and mean diastolic blood pressure (DBP was 100.2 ± 11.2 mm Hg. All the three blood pressure parameters [SBP, DBP and mean arterial pressure (MAP] were significantly higher among individuals with lower 25(OHD levels. The P values for trends in SBP, DBP and MAP were 0.009, 0.01 and 0.007, respectively. Though all the three blood pressure parameters (SBP, DBP and MAP were higher among individuals with higher BMIs, they were not achieving statistical significance. Increasing trends in PRA and PAC were noticed with lower 25(OHD and higher BMI levels. Conclusion: Vitamin D deficiency and obesity are associated with stimulation of RAAS activity. Vitamin D supplementation along with weight loss may be studied as a therapeutic strategy to reduce tissue RAS

  3. Inhibition of the Renin-Angiotensin System Post Myocardial Infarction Prevents Inflammation-Associated Acute Cardiac Rupture.

    Science.gov (United States)

    Gao, Xiao-Ming; Tsai, Alan; Al-Sharea, Annas; Su, Yidan; Moore, Shirley; Han, Li-Ping; Kiriazis, Helen; Dart, Anthony M; Murphy, Andrew J; Du, Xiao-Jun

    2017-04-01

    Inhibition of the renin-angiotensin system (RAS) is beneficial in patient management after myocardial infarction (MI). However, whether RAS inhibition also provides cardiac protection in the acute phase of MI is unclear. Male 129sv mice underwent coronary artery occlusion to induce MI, followed by treatment with losartan (L, 20 and 60 mg/kg), perindopril (P, 2 and 6 mg/kg), amlodipine (20 mg/kg as a BP-lowering agent) or vehicle as control. Drug effects on hemodynamics were examined. Effects of treatments on incidence of cardiac rupture, haematological profile, monocyte and neutrophil population in the spleen and the heart, cardiac leukocyte density, expression of inflammatory genes and activity of MMPs were studied after MI. Incidence of cardiac rupture within 2 weeks was significantly and similarly reduced by both losartan (L) and perindopril (P) in a dose-dependent manner [75% (27/36) in vehicle, 40-45% in low-dose (L 10/22, P 8/20) and 16-20% (L 5/32, P 4/20) in high-dose groups, all P infarct tissue were attenuated by losartan and/or perindopril treatment (all P acute phase of MI through blockade of splenic release of monocytes and neutrophils and consequently attenuation of systemic and regional inflammatory responses.

  4. Exercise attenuates dexamethasone-induced hypertension through an improvement of baroreflex activity independently of the renin-angiotensin system.

    Science.gov (United States)

    Constantino, Paula B; Dionísio, Thiago J; Duchatsch, Francine; Herrera, Naiara A; Duarte, Josiane O; Santos, Carlos F; Crestani, Carlos C; Amaral, Sandra L

    2017-12-01

    Dexamethasone-induced hypertension may be caused by baroreflex alterations or renin-angiotensin system (RAS) exacerbation. Aerobic training has been recommended for hypertension treatment, but the mechanisms responsible for reduction of arterial pressure (AP) in dexamethasone (DEX) treated rats are still inconclusive.This study evaluated whether mechanisms responsible for training-induced attenuation of hypertension involve changes in autonomic nervous system and in RAS components. Rats underwent aerobic training protocol on treadmill or were kept sedentary for 8 weeks. Additionally, animals were treated with DEX during the last 10 days of exercise. Body weight (BW), AP and baroreflex activity were analyzed. Tibialis anterior (TA), soleus (SOL) and left ventricle (LV) were collected for evaluation of RAS components gene expression and protein levels. Dexamethasone decreased BW (20%), caused TA atrophy (16%) and increased systolic AP (SAP, 16%) as well as decreased baroreflex activity. Training attenuated SAP increase and improved baroreflex activity, although it did not prevent DEX-induced BW reduction and muscle atrophy. Neither DEX nor training caused expressive changes in RAS components. In conclusion, exercise training was effective in attenuating hypertension induced by DEX and this response may be mediated by a better autonomic balance through an improvement of baroreflex activity rather than changes in RAS components. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The Brain Renin-Angiotensin System and Mitochondrial Function: Influence on Blood Pressure and Baroreflex in Transgenic Rat Strains

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    Manisha Nautiyal

    2013-01-01

    Full Text Available Mitochondrial dysfunction is implicated in many cardiovascular diseases, including hypertension, and may be associated with an overactive renin-angiotensin system (RAS. Angiotensin (Ang II, a potent vasoconstrictor hormone of the RAS, also impairs baroreflex and mitochondrial function. Most deleterious cardiovascular actions of Ang II are thought to be mediated by NADPH-oxidase- (NOX- derived reactive oxygen species (ROS that may also stimulate mitochondrial oxidant release and alter redox-sensitive signaling pathways in the brain. Within the RAS, the actions of Ang II are counterbalanced by Ang-(1–7, a vasodilatory peptide known to mitigate against increased oxidant stress. A balance between Ang II and Ang-(1–7 within the brain dorsal medulla contributes to maintenance of normal blood pressure and proper functioning of the arterial baroreceptor reflex for control of heart rate. We propose that Ang-(1–7 may negatively regulate the redox signaling pathways activated by Ang II to maintain normal blood pressure, baroreflex, and mitochondrial function through attenuating ROS (NOX-generated and/or mitochondrial.

  6. Involvement of Renin-Angiotensin System in Damage of Angiotensin-Converting Enzyme Inhibitor Captopril on Bone of Normal Mice.

    Science.gov (United States)

    Liu, Jin-Xin; Wang, Liang; Zhang, Yan

    2015-01-01

    This study was performed to investigate the effect of angiotensin-converting enzyme inhibitor, captopril, on bone metabolism and histology, and the action of captopril on the components of the skeletal renin-angiotensin system (RAS) and bradykinin receptor in normal male mice. The mice were orally administered captopril (10 mg/kg) for 4 weeks with vehicle-treated mice as normal control. The histology of trabecular bone at the distal femoral end was determined by hematoxylin & eosin, Safranin O and Masson-Trichrome staining. The captopril-treated mice showed a decreased level of testosterone (pCaptopril has detrimental effects on trabecular bone as demonstrated by the loss of cancellous bone mass and network connections as well as changes to the chondrocytes zone. The expression of angiotensin-converting enzyme (pcaptopril treatment. Thus, the potential underlying mechanism of the damage of captopril on bone can be attributed the increased activity of local bone RAS and the activation of bradykinin receptor.

  7. Farmácia Popular Program: pharmaceutical market analysis of antihypertensive acting on the renin-angiotensin system medicines.

    Science.gov (United States)

    Silva, Rondineli Mendes da; Chaves, Gabriela Costa; Chaves, Luisa Arueira; Campos, Mônica Rodrigues; Luiza, Vera Lucia; Bertoldi, Andréa Dâmaso; Ross-Degnan, Dennis; Emmerick, Isabel Cristina Martins

    2017-08-01

    This paper aims to analyse changes in the retail pharmaceutical market following policy changes in the Farmácia Popular Program (FP), a medicines subsidy program in Brazil. The retrospective longitudinal analyses focus on therapeutic class of agents acting on the renin-angiotensin system. Data obtained from QuintilesIMS (formerly IMS Health) included private retail pharmacy sales volume (pharmaceutical units) and sales values from 2002 to 2013. Analyses evaluated changes in market share following key FP policy changes. The therapeutic class was selected due to its relevance to hypertension treatment. Market share was analysed by therapeutic sub-classes and by individual company. Losartan as a single product accounted for the highest market share among angiotensin II antagonists. National companies had higher sales volume during the study period, while multinational companies had higher sales value. Changes in pharmaceutical market share coincided with the inclusion of specific products in the list of medicines covered by FP and with increases in or exemption from patient copayment.

  8. Angioedema Triggered by Medication Blocking the Renin/Angiotensin System: Retrospective Study Using the French National Pharmacovigilance Database.

    Science.gov (United States)

    Faisant, Charles; Armengol, Guillaume; Bouillet, Laurence; Boccon-Gibod, Isabelle; Villier, Céline; Lévesque, Hervé; Cottin, Judith; Massy, Nathalie; Benhamou, Ygal

    2016-01-01

    Bradykinin-mediated angioedema (AE) is a rare side effect of some medications, including angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). In France, side-effects to treatments are reported to the national pharmacovigilance database. The national MedDRA database was searched using the term "angioedema". Patients were included if they met the clinical criteria corresponding to bradykinin-mediated AE, if their C1-inhibitor levels were normal, and if they were treated with an ACEi or an ARB. 7998 cases of AE were reported between 1994 and 2013. Among these, 112 met the criteria for bradykinin-mediated AE with normal C1-inhibitor levels. On the 112 drug-AE, patients were treated with an ARB in 21% of cases (24 patients), or an ACEi in 77% of cases (88 patients), in combination with another treatment in 17 cases (mTORi for 3 patients, iDPP-4 for 1 patient, hormonal treatment for 7 patients). ENT involvement was reported in 90% of cases (tongue: 48.2%, larynx: 23.2%). The median duration of treatment before the first attack was 720 days, and the mean duration of attacks was 36.6 h. Forty-one percent (19/46) of patients relapsed after discontinuing treatment. Angioedema triggered by medication blocking the renin/angiotensin system is rare but potentially severe, with a high risk of recurrence despite cessation of the causative drug.

  9. ROLE OF RENIN-ANGIOTENSIN SYSTEM AND OXIDATIVE STRESS AND INFLAMMATION TO THE BLOOD PRESSURE CONTROL IN YOUNG SUBJECTS

    Directory of Open Access Journals (Sweden)

    Emiko Sato

    2012-06-01

    Full Text Available Renin-Angiotensin System (RAS, oxidative stress and inflammation is involved in the pathogenesis of hypertension and salt sensitivity of hypertension. The present study was designed to evaluate the role of RAS, oxidative stress and inflammation to the regulation of blood pressure in young subjects. 111 young students (19.2±0.8 years old who have taken health checkup were randomly selected for the study. Urinary excretions of angiotensinogen (AGT, oxidative stress (TBARS, and inflammatory markers (MCP-1 were analyzed. Urinary excretions of these parameters were estimated by 24-hour urinary creatinine excretion, age, height and body weight. Subjects were divided to two groups based on the blood pressure: below 140/90 mmHg (Normal and over 140/90 mmHg (High. Blood pressure was significantly increased with increased BMI. Urinary AGT, TBARS, and MCP-1 of high blood pressure group were significantly (p<0.05 increased compared to those of normal blood pressure. Urinary AGT has significant positive correlation with urinary TBARS, though it did not have a significant correlation with MCP-1. Estimated 24-h urinary Na excretion was significantly increased with increased urinary MCP-1, and TBARS. These results indicate that increase in blood pressure is accompanied with RAS, oxidative stress, and inflammation in young subjects, which is associated with salt intake.

  10. Farmácia Popular Program: pharmaceutical market analysis of antihypertensive acting on the renin-angiotensin system medicines

    Directory of Open Access Journals (Sweden)

    Rondineli Mendes da Silva

    Full Text Available Abstract This paper aims to analyse changes in the retail pharmaceutical market following policy changes in the Farmácia Popular Program (FP, a medicines subsidy program in Brazil. The retrospective longitudinal analyses focus on therapeutic class of agents acting on the renin-angiotensin system. Data obtained from QuintilesIMS (formerly IMS Health included private retail pharmacy sales volume (pharmaceutical units and sales values from 2002 to 2013. Analyses evaluated changes in market share following key FP policy changes. The therapeutic class was selected due to its relevance to hypertension treatment. Market share was analysed by therapeutic sub-classes and by individual company. Losartan as a single product accounted for the highest market share among angiotensin II antagonists. National companies had higher sales volume during the study period, while multinational companies had higher sales value. Changes in pharmaceutical market share coincided with the inclusion of specific products in the list of medicines covered by FP and with increases in or exemption from patient copayment.

  11. Side Chain-oxidized Oxysterols Regulate the Brain Renin-Angiotensin System through a Liver X Receptor-dependent Mechanism*

    Science.gov (United States)

    Mateos, Laura; Ismail, Muhammad-Al-Mustafa; Gil-Bea, Francisco-Javier; Schüle, Rebecca; Schöls, Ludger; Heverin, Maura; Folkesson, Ronnie; Björkhem, Ingemar; Cedazo-Mínguez, Angel

    2011-01-01

    Disturbances in cholesterol metabolism have been associated with hypertension and neurodegenerative disorders. Because cholesterol metabolism in the brain is efficiently separated from plasma cholesterol by the blood-brain barrier (BBB), it is an unsolved paradox how high blood cholesterol can cause an effect in the brain. Here, we discuss the possibility that cholesterol metabolites permeable to the BBB might account for these effects. We show that 27-hydroxycholesterol (27-OH) and 24S-hydroxycholesterol (24S-OH) up-regulate the renin-angiotensin system (RAS) in the brain. Brains of mice on a cholesterol-enriched diet showed up-regulated angiotensin converting enzyme (ACE), angiotensinogen (AGT), and increased JAK/STAT activity. These effects were confirmed in in vitro studies with primary neurons and astrocytes exposed to 27-OH or 24S-OH, and were partially mediated by liver X receptors. In contrast, brain RAS activity was decreased in Cyp27a1-deficient mice, a model exhibiting reduced 27-OH production from cholesterol. Moreover, in humans, normocholesterolemic patients with elevated 27-OH levels, due to a CYP7B1 mutation, had markers of activated RAS in their cerebrospinal fluid. Our results demonstrate that side chain-oxidized oxysterols are modulators of brain RAS. Considering that levels of cholesterol and 27-OH correlate in the circulation and 27-OH can pass the BBB into the brain, we suggest that this cholesterol metabolite could be a link between high plasma cholesterol levels, hypertension, and neurodegeneration. PMID:21628469

  12. Study of prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves

    Directory of Open Access Journals (Sweden)

    Divya Bhadoo

    2015-01-01

    Full Text Available Aims: Study on prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves. Materials and Methods: Antenatally diagnosed hydronephrosis patients were included. Postnatally, they were divided into two groups, posterior urethral valve (PUV and non-PUV. The studied parameters were: Gestational age at detection, surgical intervention, ultrasound findings, cord blood and follow up plasma renin activity (PRA values, vesico-ureteric reflux (VUR, renal scars, and glomerular filtration rate (GFR. Results: A total of 25 patients were included, 10 PUV and 15 non-PUV. All infants with PUV underwent primary valve incision. GFR was less than 60 ml/min/1.73 m 2 body surface area in 4 patients at last follow-up. Keyhole sign, oligoamnios, absent bladder cycling, and cortical cysts were not consistent findings on antenatal ultrasound in PUV. Cord blood PRA was significantly higher (P < 0.0001 in PUV compared to non-PUV patients. Gestational age at detection of hydronephrosis, cortical cysts, bladder wall thickness, and amniotic fluid index were not significantly correlated with GFR while PRA could differentiate between poor and better prognosis cases with PUV. Conclusions: Ultrasound was neither uniformly useful in diagnosing PUV antenatally, nor differentiating it from cases with non-PUV hydronephrosis. In congenital hydronephrosis, cord blood PRA was significantly higher in cases with PUV compared to non-PUV cases and fell significantly after valve ablation. Cord blood PRA could distinguish between poor and better prognosis cases with PUV.

  13. Role of MicroRNAs in Renin-Angiotensin-Aldosterone System-Mediated Cardiovascular Inflammation and Remodeling

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    Maricica Pacurari

    2015-01-01

    Full Text Available MicroRNAs are endogenous regulators of gene expression either by inhibiting translation or protein degradation. Recent studies indicate that microRNAs play a role in cardiovascular disease and renin-angiotensin-aldosterone system- (RAAS- mediated cardiovascular inflammation, either as mediators or being targeted by RAAS pharmacological inhibitors. The exact role(s of microRNAs in RAAS-mediated cardiovascular inflammation and remodeling is/are still in early stage of investigation. However, few microRNAs have been shown to play a role in RAAS signaling, particularly miR-155, miR-146a/b, miR-132/122, and miR-483-3p. Identification of specific microRNAs and their targets and elucidating microRNA-regulated mechanisms associated RAS-mediated cardiovascular inflammation and remodeling might lead to the development of novel pharmacological strategies to target RAAS-mediated vascular pathologies. This paper reviews microRNAs role in inflammatory factors mediating cardiovascular inflammation and RAAS genes and the effect of RAAS pharmacological inhibition on microRNAs and the resolution of RAAS-mediated cardiovascular inflammation and remodeling. Also, this paper discusses the advances on microRNAs-based therapeutic approaches that may be important in targeting RAAS signaling.

  14. Renal Kallikrein Activation and Renoprotection after Dual Blockade of Renin-Angiotensin System in Diet-Induced Diabetic Nephropathy

    Science.gov (United States)

    Zou, Xia; Zhang, Xiao-xi; Liu, Xin-yu; Li, Rong; Wang, Min; Wu, Wei-jie; Sui, Yi; Zhao, Hai-lu

    2015-01-01

    Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS) on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN). Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF-) β and α-smooth muscle action (SMA). Results. DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (all P < 0.05). Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, and α-SMA. Conclusion. The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response. PMID:25918729

  15. Efficacy of renin-angiotensin system (RAS) blockers on cardiovascular and renal outcomes in patients with type 2 diabetes.

    Science.gov (United States)

    Cao, Zemin; Cooper, Mark E

    2012-08-01

    Cardiovascular disease is the predominant cause of morbidity in people with type 2 diabetes. Hypertension frequently coexists with diabetes and substantially increases the risk of developing end-organ damage. Controlling hypertension in patients with diabetes is therefore critical to reducing microvascular and macrovascular complications. Agents that block the renin-angiotensin system are increasingly used in patients with diabetes based on their cardiovascular and renoprotective effects, in addition to their direct effects on reducing blood pressure. Telmisartan, an angiotensin II receptor blocker (ARB), has a number of distinguishing pharmacological properties such as having the longest half-life and highest lipophilicity in its class. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET(®)) trial showed that telmisartan reduces cardiovascular morbidity (including myocardial infarction and stroke) in subjects with a broad spectrum of cardiovascular risk factors, including type 2 diabetes. Telmisartan is the only ARB indicated for the reduction of cardiovascular morbidity in patients with diabetes and end-organ damage, as well as in patients without diabetes but with a history of coronary artery disease, peripheral artery disease, or previous stroke. Trials of telmisartan in patients with diabetes and varying degrees of nephropathy also suggest that this drug can slow the progression of renal disease, an effect that appears to be at least partly independent of reduction in blood pressure. Telmisartan is therefore an important therapeutic option for optimizing cardiovascular and renal protection in the type 2 diabetic population.

  16. [Cardiovascular risk study in patients with renin-angiotensin system blockade by means of the proteone of circulating extracellular vesicles].

    Science.gov (United States)

    de la Cuesta, F; Baldan-Martin, M; Mourino-Alvarez, L; Sastre-Oliva, T; Alvarez-Llamas, G; Gonzalez-Calero, L; Ruiz-Hurtado, G; Segura, J; Vivanco, F; Ruilope, L M; Barderas, M G

    2016-01-01

    Extracellular vesicles (EVs) are released to the bloodstream by certain cell types due to transport, activation and cell death processes. Blood count of EVs from platelet and endothelial origin has been proved to be a cardiovascular risk biomarker. Thus, EVs proteome might reflect the underlying cellular processes in hypertensive patients with albuminuria. Protein content of circulating EVs was analyzed by liquid chromatography coupled to mass spectrometry. EVs were isolated by an ultracentrifugation protocol optimized in order to avoid contamination by blood plasma proteins. Purity of the isolated fraction was verified by electronic and confocal microscopy, and by flow cytometry. We hereby show a method to isolate circulating EVs from hypertensive patients with/without albuminuria with high yield and purity. Besides, we provide a reference proteome of the EVs of these patients, composed of 2,463 proteins, and prove that the proteins carried by these vesicles are associated with crucial processes involved in the inherent cardiovascular risk. The proteome of circulating EVs is an interesting source of indicators in the evaluation of cardiovascular risk in hypertensive patients with renin-angiotensin system blockage. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

  17. Activation of renin-angiotensin-aldosterone system (RAAS) in the lung of smoking-induced pulmonary arterial hypertension (PAH) rats.

    Science.gov (United States)

    Yuan, Yi-Ming; Luo, Li; Guo, Zhen; Yang, Ming; Ye, Ren-Song; Luo, Chuan

    2015-06-01

    To explore the role of the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of pulmonary arterial hypertension (PAH) induced by chronic exposure to cigarette smoke. 48 healthy male SD rats were randomly divided into four groups (12/group): control group (group A); inhibitor alone group (group B); cigarette induction group (group C); cigarette induction + inhibitor group (group D). After the establishment of smoking-induced PAH rat model, the right ventricular systolic pressure (RVSP) was detected using an inserted catheter; western blotting was used to detect the protein expression of angiotensin-converting enzyme-2 (ACE2) and angiotensin-converting enzyme (ACE); expression levels of angiotensin II (AngII) in lung tissue were measured by radioimmunoassay. After six months of cigarette exposure, the RVSP of chronic cigarette induction group was significantly higher than that of the control group; expression levels of AngII and ACE increased in lung tissues, but ACE2 expression levels reduced. Compared with cigarette exposure group, after losartan treatment, RVSP, ACE and AngII obviously decreased (Psmoking-induced PAH. © The Author(s) 2015.

  18. Combined effects of aging and inflammation on renin-angiotensin system mediate mitochondrial dysfunction and phenotypic changes in cardiomyopathies.

    Science.gov (United States)

    Burks, Tyesha N; Marx, Ruth; Powell, Laura; Rucker, Jasma; Bedja, Djahida; Heacock, Elisa; Smith, Barbara J; Foster, D Brian; Kass, David; O'Rourke, Brian; Walston, Jeremy D; Abadir, Peter M

    2015-05-20

    Although the effects of aging and inflammation on the health of the cardiac muscle are well documented, the combined effects of aging and chronic inflammation on cardiac muscle are largely unknown. The renin-angiotensin system (RAS) has been linked independently to both aging and inflammation, but is understudied in the context of their collective effect. Thus, we investigated localized cardiac angiotensin II type I and type II receptors (AT(1)R, AT(2)R), downstream effectors, and phenotypic outcomes using mouse models of the combination of aging and inflammation and compared it to a model of aging and a model of inflammation. We show molecular distinction in the combined effect of aging and inflammation as compared to each independently. The combination maintained an increased AT(1)R:AT(2)R and expression of Nox2 and exhibited the lowest activity of antioxidants. Despite signaling pathway differences, the combined effect shared phenotypic similarities with aging including oxidative damage, fibrosis, and hypertrophy. These phenotypic similarities have dubbed inflammatory conditions as premature aging, but they are, in fact, molecularly distinct. Moreover, treatment with an AT(1)R blocker, losartan, selectively reversed the signaling changes and ameliorated adverse phenotypic effects in the combination of aging and inflammation as well as each independently.

  19. Urinary renin-angiotensin markers in polycystic kidney disease

    NARCIS (Netherlands)

    Salih, Mahdi; Bovee, Dominique M.; Roksnoer, Lodi C. W.; Casteleijn, Niek F.; Bakker, Stephan J. L.; Gansevoort, Ronald T.; Zietse, Robert; Danser, A. H. Jan; Hoorn, Ewout J.

    2017-01-01

    In autosomal dominant polycystic kidney disease (ADPKD), activation of the renin-angiotensin aldosterone system (RAAS) may contribute to hypertension and disease progression. Although previous studies have focused on circulating RAAS components, preliminary evidence suggests that APDKD may increase

  20. Nifedipine-sensitive blood pressure component in hypertensive models characterized by high activity of either sympathetic nervous system or renin-angiotensin system

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Dobešová, Zdenka; Behuliak, Michal; Pintérová, Mária; Kuneš, Jaroslav; Vaněčková, Ivana

    2014-01-01

    Roč. 63, č. 1 (2014), s. 13-26 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/09/0336; GA ČR(CZ) GAP304/12/0259 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : voltage-gated caclium channels * sympathetic nervous system * renin-angiotensin system * nitric oxide Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.293, year: 2014

  1. Maternal Dexamethasone Treatment Alters Tissue and Circulating Components of the Renin-Angiotensin System in the Pregnant Ewe and Fetus

    Science.gov (United States)

    Jellyman, Juanita K.; De Blasio, Miles J.; Johnson, Emma; Giussani, Dino A.; Broughton Pipkin, Fiona; Fowden, Abigail L.

    2015-01-01

    Antenatal synthetic glucocorticoids promote fetal maturation in pregnant women at risk of preterm delivery and their mechanism of action may involve other endocrine systems. This study investigated the effect of maternal dexamethasone treatment, at clinically relevant doses, on components of the renin-angiotensin system (RAS) in the pregnant ewe and fetus. From 125 days of gestation (term, 145 ± 2 d), 10 ewes carrying single fetuses of mixed sex (3 female, 7 male) were injected twice im, at 10–11 pm, with dexamethasone (2 × 12 mg, n = 5) or saline (n = 5) at 24-hour intervals. At 10 hours after the second injection, maternal dexamethasone treatment increased angiotensin-converting enzyme (ACE) mRNA levels in the fetal lungs, kidneys, and heart and ACE concentration in the circulation and lungs, but not kidneys, of the fetuses. Fetal cardiac mRNA abundance of angiotensin II (AII) type 2 receptor decreased after maternal dexamethasone treatment. Between the two groups of fetuses, there were no significant differences in plasma angiotensinogen or renin concentrations; in transcript levels of renal renin, or AII type 1 or 2 receptors in the lungs and kidneys; or in pulmonary, renal or cardiac protein content of the AII receptors. In the pregnant ewes, dexamethasone administration increased pulmonary ACE and plasma angiotensinogen, and decreased plasma renin, concentrations. Some of the effects of dexamethasone treatment on the maternal and fetal RAS were associated with altered insulin and thyroid hormone activity. Changes in the local and circulating RAS induced by dexamethasone exposure in utero may contribute to the maturational and tissue-specific actions of antenatal glucocorticoid treatment. PMID:26039155

  2. The role of tissue renin angiotensin aldosterone system in the development of endothelial dysfunction and arterial stiffness

    Directory of Open Access Journals (Sweden)

    Annayya R Aroor

    2013-10-01

    Full Text Available Epidemiological studies support the notion that arterial stiffness is an independent predictor of adverse cardiovascular events contributing significantly to systolic hypertension, impaired ventricular-arterial coupling and diastolic dysfunction, impairment in myocardial oxygen supply and demand, and progression of kidney disease. Although arterial stiffness is associated with aging, it is accelerated in the presence of obesity and diabetes. The prevalence of arterial stiffness parallels the increase of obesity that is occurring in epidemic proportions and is partly driven by a sedentary life style and consumption of a high fructose, high salt and high fat western diet. Although the underlying mechanisms and mediators of arterial stiffness are not well understood, accumulating evidence supports the role of insulin resistance and endothelial dysfunction. The local tissue renin angiotensin aldosterone system (RAAS in the vascular tissue and immune cells and perivascular adipose tissue is recognized as an important element involved in endothelial dysfunction which contributes significantly to arterial stiffness. Activation of vascular RAAS is seen in humans and animal models of obesity and diabetes, and associated with enhanced oxidative stress and inflammation in the vascular tissue. The cross talk between angiotensin and aldosterone underscores the importance of mineralocorticoid receptors in modulation of insulin resistance, decreased bioavailability of nitric oxide, endothelial dysfunction and arterial stiffness. In addition, both innate and adaptive immunity are involved in this local tissue activation of RAAS. In this review we will attempt to present a unifying mechanism of how environmental and immunological factors are involved in this local tissue RAAS activation, and the role of this process in the development of endothelial dysfunction and arterial stiffness and targeting tissue RAAS activation.

  3. The Renin-Angiotensin-Aldosterone system in patients with depression compared to controls – a sleep endocrine study

    Directory of Open Access Journals (Sweden)

    Künzel Heike

    2003-10-01

    Full Text Available Abstract Background Hypercortisolism as a sign of hypothamamus-pituitary-adrenocortical (HPA axis overactivity and sleep EEG changes are frequently observed in depression. Closely related to the HPA axis is the renin-angiotensin-aldosterone system (RAAS as 1. adrenocorticotropic hormone (ACTH is a common stimulus for cortisol and aldosterone, 2. cortisol release is suppressed by mineralocorticoid receptor (MR agonists 3. angiotensin II (ATII releases CRH and vasopressin from the hypothalamus. Furthermore renin and aldosterone secretion are synchronized to the rapid eyed movement (REM-nonREM cycle. Methods Here we focus on the difference of sleep related activity of the RAAS between depressed patients and healthy controls. We studied the nocturnal plasma concentration of ACTH, cortisol, renin and aldosterone, and sleep EEG in 7 medication free patients with depression (1 male, 6 females, age: (mean +/-SD 53.3 ± 14.4 yr. and 7 age matched controls (2 males, 5 females, age: 54.7 ± 19.5 yr.. After one night of accommodation a polysomnography was performed between 23.00 h and 7.00 h. During examination nights blood samples were taken every 20 min between 23.00 h and 7.00 h. Area under the curve (AUC for the hormones separated for the halves of the night (23.00 h to 3.00 h and 3.00 h to 7.00 h were used for statistical analysis, with analysis of co variance being performed with age as a covariate. Results No differences in ACTH and renin concentrations were found. For cortisol, a trend to an increase was found in the first half of the night in patients compared to controls (p Conclusion Hyperaldosteronism could be a sensitive marker for depression. Further our findings point to an altered renal mineralocorticoid sensitivity in patients with depression.

  4. Renin angiotensin system blockers-associated angioedema in the Thai population: analysis from Thai National Pharmacovigilance Database.

    Science.gov (United States)

    Win, Thet Su Zin; Chaiyakunapruk, Nathorn; Suwankesawong, Wimon; Dilokthornsakul, Piyameth; Nathisuwan, Surakit

    2015-09-01

    Renin-angiotensin-aldosterone system (RAS) blockers are commonly used for cardiovascular diseases. Currently, little information exists for the Asian population on angioedema, a rare yet serious adverse event. This study aimed to describe characteristics of RAS blockers-associated angioedema (RASBA) in Thai patients. A retrospective study using the national pharmacovigilance database of Thailand was undertaken. Cases indicating the presence of angioedema with RAS blockers uses from 1984-2011 were identified. Patient demographics, co-morbidities, concomitant drugs, information for the RAS blockers and angioedema were obtained as well as causality assessment and quality of reports. A total of 895 cases were identified. Mean age was 59.9+12.8 years and 66.5% being female. Most angioedema events (48.6%) occurred during the first week of treatment. Angiotensin converting enzyme inhibitors (87.7%) were the most commonly implicated agents followed by angiotensin receptor blockers (10.5%), aldosterone antagonist (2.1%) and direct renin inhibitor (0.2%). Out of the 895 cases incorporated in this study, 165 (18.4%) were classified as serious events and resulted in hospitalization. The overall case fatality rate was 0.4%. Respiratory disturbance occurred in 46 cases (5.1%). Patients with respiratory complications tended to be younger (53.4+13.9 vs 60.3+12.7 years old; p=0.002) and with higher frequency of allergy history (26.1% vs 14.7%; p=0.032) compared to those without respiratory complications. Based on multivariate logistic regression, the adjusted OR for history of allergy was 2.23 (95%CI: 1.04 - 4.78, p = 0.041). RASBA in Thai population occurred mostly in elderly female patients and often led to hospitalization. Since large number of patients is regularly exposed to RAS-blockers, a nationwide attempt to raise awareness of clinicians when prescribing RAS-blockers is prudent.

  5. Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System

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    Therese Featherston

    2016-09-01

    Full Text Available Aim We have recently identified and characterized cancer stem cell (CSC subpopulations within moderately differentiated buccal mucosal squamous cell carcinoma (MDBMSCC. We hypothesized that these CSCs express components of the renin-angiotensin system (RAS.Methods 3,3-Diaminobenzidine (DAB immunohistochemical (IHC staining was performed on formalin-fixed paraffin-embedded MDBMSCC samples to investigate the expression of the components of the RAS: pro(renin receptor (PRR, angiotensin converting enzyme (ACE, angiotensin II receptor 1 (ATIIR1 and angiotensin II receptor 2 (ATIIR2. NanoString mRNA gene expression analysis and Western Blotting (WB were performed on snap-frozen MDBMSCC samples to confirm gene expression and translation of these transcripts, respectively. Double immunofluorescent (IF IHC staining of these components of the RAS with the embryonic stem cell markers OCT4 or SALL4 was performed to demonstrate their localization in relation to the CSC subpopulations within MDBMSCC.Results DAB IHC staining demonstrated expression of PRR, ACE, ATIIR1 and ATIIR2 in MDBMSCC. IF IHC staining showed that PRR was expressed by the CSC subpopulations within the tumor nests, the peri-tumoral stroma and the endothelium of the microvessels within the peri-tumoral stroma. ATIIR1 and ATIIR2 were localized to the CSC subpopulations within the tumor nests and the peri-tumoral stroma, while ACE was localized to the endothelium of the microvessels within the peri-tumoral stroma. WB and NanoString analyses confirmed protein expression and transcription activation of PRR, ACE and ATIIR1 but not of ATIIR2, respectively.

  6. Association of renin-angiotensin system genes polymorphism with progression of diabetic nephropathy in patients with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ilić Vesna

    2014-01-01

    Full Text Available Background/Aim. Diabetic nephropathy (DN as a major microvascular complication of diabetes mellitus (DM include a progressive increase in urinary albumin excretion in association with an increase in blood pressure and to end stage renal failure. Hypertension connected with renin-angiotensin system (RAS hyperactivity and corresponding genotypes, angiotensinogen (AGT, angiotensine-converting enzyme (ACE and angiotensin II type 1 receptor (AT1R, predispose the increasing risk of DN. The aim of this study was to assess the distribution of AGT, ACE and AT1R gene polymorphisms in patients with type 1 DM according to the level of DN and patients clinical characteristics. Methods. The study included 79 type 1 diabetic patients. Inclusion criteria were: age between 20-40, duration of diabetes > 5 years, and no other severe diseases. Clinical characteristics were gained from interviewing the patients. Polymorphism was detected by polymerase chain reaction (PCR and restriction fragment length polymorphism using restriction enzymes Psy I (Tth 111 I and Hae III. Results. The patients with proteinuria compared with normo- and microalbuminuric patients, highly differed in age, diabetes duration, blood pressure level, hypertension, rethynopathy and urinary albumin excretion values (p < 0.001. No statistically significant difference between the groups was found for the ACE and AT1R gene polymorphisms distribution. The presence of TT genotype of the M235T polymorphism was significantly higher in the group with proteinuria (p < 0.05. The patients with hypertension raised nephropathy 5.2 times higher (OR = 5.20, p < 0.05 while carriers of TT allel developed nephropathy 28.38 times higher (OR = 28.389, p < 0.01 than those with MM genotype. Conclusion. Increased association of hypertension and TT angiotensinogen gene polymorphism in patients with diabetes mellitus with proteinuria could be a significant marker of diabetic nephropathy.

  7. Renin-angiotensin system blockade reduces cardiovascular events in nonheart failure, stable patients with prior coronary intervention.

    Science.gov (United States)

    Choi, Young; Lim, Sungmin; Lee, Kwan Yong; Park, Ha-Wook; Byeon, Jaeho; Hwang, Byung-Hee; Kim, Jin Jin; Oh, Yong-Seog; Youn, Ho-Joong; Jung, Wook Sung; Seung, Ki-Bae; Chang, Kiyuk

    2018-02-27

    The effects of renin-angiotensin system (RAS) blockade on the clinical outcome in patients with stable coronary artery disease (SCAD) are conflicting. We evaluated the long-term effects of RAS blockers (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker) on the clinical outcomes in patients with SCAD without heart failure (HF) who underwent percutaneous coronary intervention (PCI) with drug-eluting stent using a large-scale, multicenter, prospective cohort registry. A total of 5722 patients with SCAD were enrolled and divided into two groups according to the use of RAS blockers after PCI: RAS blocker group included 4070 patients and no RAS blocker group included 1652 patients. Exclusion criteria were left ventricular ejection fraction less than 50% and the history of HF or myocardial infarction. A major adverse cardiovascular event (MACE) was defined as a composite of cardiovascular death, nonfatal myocardial infarction, and stroke. During a median follow-up of 29.7 months, RAS blockers were associated with a significant reduction in the risk of MACE [adjusted hazard ratio (HR): 0.781; 95% confidence interval (CI): 0.626-0.975; P=0.015] and all-cause death (adjusted HR: 0.788; 95% CI: 0.627-0.990; P=0.041) but did not affect the risk of coronary revascularization. In the propensity score matched cohort, overall findings were consistent (MACE: adjusted HR: 0.679; 95% CI: 0.514-0.897; P=0.006; all-cause death: adjusted HR: 0.723; 95% CI: 0.548-0.954; P=0.022), and the benefit of RAS blockade was maintained in all predefined subgroups. This study demonstrated that RAS blockers were effective preventive therapies for reducing long-term cardiovascular events in patients with SCAD without HF who underwent PCI.

  8. Renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.

    Directory of Open Access Journals (Sweden)

    Eliete Dalla Corte Frantz

    Full Text Available BACKGROUND: The associations between obesity, hypertension and diabetes are well established, and the renin-angiotensin system (RAS may provide a link among them. The effect of RAS inhibition on type 2 diabetes is still unclear; however, RAS seems to play an important role in the regulation of the pancreas and glucose intolerance of mice fed high-fat (HF diet. METHODS: C57BL/6 mice fed a HF diet (8 weeks were treated with aliskiren (50 mg/kg/day, enalapril (30 mg/kg/day or losartan (10 mg/kg/day for 6 weeks, and the protective effects were extensively compared among groups by morphometry, stereological tools, immunostaining, Western blotting and hormonal analysis. RESULTS: All RAS inhibitors significantly attenuated the increased blood pressure in mice fed a HF diet. Treatment with enalapril, but not aliskiren or losartan, significantly attenuated body mass (BM gain, glucose intolerance and insulin resistance, improved the alpha and beta cell mass and prevented the reduction of plasma adiponectin. Furthermore, enalapril treatment improved the protein expression of the pancreatic islet Pdx1, GLUT2, ACE2 and Mas receptors. Losartan treatment showed the greatest AT2R expression. CONCLUSION: Our findings indicate that ACE inhibition with enalapril attenuated several of the deleterious effects of the HF diet. In summary, enalapril appears to be responsible for the normalization of islet morphology and function, of alpha and beta cell mass and of Pdx1 and GLUT2 expression. These protective effects of enalapril were attributed, primarily, to the reduction in body mass gain and food intake and the enhancement of the ACE2/Ang (1-7 /Mas receptor axis and adiponectin levels.

  9. Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life.

    Science.gov (United States)

    Wang, Kimberley C W; Brooks, Doug A; Summers-Pearce, Brooke; Bobrovskaya, Larisa; Tosh, Darran N; Duffield, Jaime A; Botting, Kimberley J; Zhang, Song; Caroline McMillen, I; Morrison, Janna L

    2015-02-01

    Low birth weight (LBW) is associated with increased risk of adult cardiovascular disease and this association may be partly a consequence of early programming of the renin-angiotensin system (RAS). We investigated the effects of LBW on expression of molecules in the RAS and cardiac tissue remodeling. Left ventricular samples were collected from the hearts of 21 days old lambs that were born average birth weight (ABW) and LBW. Cardiac mRNA expression was quantified using real-time RT-PCR and protein expression was quantified using Western blotting. DNA methylation and histone acetylation were assessed by combined bisulfite restriction analysis and chromatin immunoprecipitation, respectively. There were increased plasma renin activity, angiotensin I (ANGI), and ANGII concentrations in LBW compared to ABW lambs at day 20. In LBW lambs, there was increased expression of cardiac ACE2 mRNA, decreased ANGII receptor type 1 (AT1R) protein, and acetylation of histone H3K9 of the AT1R promoter but no changes in AT1R mRNA expression and AT1R promoter DNA methylation. There was no difference in the abundance of proteins involved in autophagy or fibrosis. BIRC5 and VEGF mRNA expression was increased; however, the total length of the capillaries was decreased in the hearts of LBW lambs. Activation of the circulating and local cardiac RAS in neonatal LBW lambs may be expected to increase cardiac fibrosis, autophagy, and capillary length. However, we observed only a decrease in total capillary length, suggesting a dysregulation of the RAS in the heart of LBW lambs and this may have significant implications for heart health in later life. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  10. Characterization of the cardiac renin angiotensin system in oophorectomized and estrogen-replete mRen2.Lewis rats.

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    Hao Wang

    Full Text Available The cardioprotective effects of estrogen are well recognized, but the mechanisms remain poorly understood. Accumulating evidence suggests that the local cardiac renin-angiotensin system (RAS is involved in the development and progression of cardiac hypertrophy, remodeling, and heart failure. Estrogen attenuates the effects of an activated circulating RAS; however, its role in regulating the cardiac RAS is unclear. Bilateral oophorectomy (OVX; n = 17 or sham-operation (Sham; n = 13 was performed in 4-week-old, female mRen2.Lewis rats. At 11 weeks of age, the rats were randomized and received either 17 β-estradiol (E2, 36 µg/pellet, 60-day release, n = 8 or vehicle (OVX-V, n = 9 for 4 weeks. The rats were sacrificed, and blood and hearts were used to determine protein and/or gene expression of circulating and tissue RAS components. E2 treatment minimized the rise in circulating angiotensin (Ang II and aldosterone produced by loss of ovarian estrogens. Chronic E2 also attenuated OVX-associated increases in cardiac Ang II, Ang-(1-7 content, chymase gene expression, and mast cell number. Neither OVX nor OVX+E2 altered cardiac expression or activity of renin, angiotensinogen, angiotensin-converting enzyme (ACE, and Ang II type 1 receptor (AT1R. E2 treatment in OVX rats significantly decreased gene expression of MMP-9, ACE2, and Ang-(1-7 mas receptor, in comparison to sham-operated and OVX littermates. E2 treatment appears to inhibit upsurges in cardiac Ang II expression in the OVX-mRen2 rat, possibly by reducing chymase-dependent Ang II formation. Further studies are warranted to determine whether an E2-mediated reduction in cardiac chymase directly contributes to this response in OVX rats.

  11. Renin-angiotensin-aldosterone system inhibitors lower hemoglobin and hematocrit only in renal transplant recipients with initially higher levels.

    Science.gov (United States)

    Mikolasevic, I; Zaputovic, L; Zibar, L; Begic, I; Zutelija, M; Klanac, A; Majurec, I; Simundic, T; Minazek, M; Orlic, L

    2016-04-01

    We have analyzed the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on evolution of hemoglobin (Hb) and hematocrit (Htc) levels as well as on the evaluation of kidney graft function in stable renal transplant recipients (RTRs) in respect with initially higher or lower Hb and Htc values. The study group comprised of 270 RTRs with stable graft function. Besides other prescribed antihypertensive therapy, 169 of them have been taking RAAS inhibitors. We wanted to analyze the effect of the use of RAAS inhibitors on Hb and Htc in patients with initially higher or lower Hb/Htc values. For this analysis, only RTRs that were taking RAAS inhibitors were stratified into two groups: one with higher Hb and Htc (initial Hb≥150g/L and Htc≥45%) and another one with lower Hb and Htc (initial Hb<150g/L and Htc<45%) values. Thirty-four RTRs with initially higher Hb and 41 RTRs with initially higher Htc had a statistically significant decrease in Hb (p=0.006) and Htc (p<0.0001) levels after 12-months of follow-up. In the group of patients with initially lower Hb (135 RTRs) and Htc (128 RTRs) there was a significant increase in Hb (p=0.0001) and Htc (p=0.004) levels through the observed period. The use of RAAS inhibitors has been associated with a trend of slowing renal insufficiency in RTRs (p=0.03). RAAS inhibitors lower Hb and Htc only in RTRs with initially higher levels. In patients with initially lower Hb and Htc levels, the use of these drugs is followed by beneficial impact on erythropoiesis and kidney graft function. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  12. Epistatic Effects of Polymorphisms in Genes from the Renin-Angiotensin, Bradykinin, and Fibrinolytic Systems on Plasma t-PA and PAI-1 Levels

    Science.gov (United States)

    Asselbergs, Folkert W.; Williams, Scott M.; Hebert, Patricia R.; Coffey, Christopher S.; Hillege, Hans L.; Navis, Gerjan; Vaughan, Douglas E.; van Gilst, Wiek H.; Moore, Jason H.

    2007-01-01

    Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) directly influence thrombus formation and degradation and thereby risk for arterial thrombosis. Activation of the renin-angiotensin system has been linked to the production of PAI-1 expression via the angiotensin II type 1 receptor (AT1R). In addition, bradykinin can induce the release of t-PA through a B2 receptor mechanism. In the present study, we aimed to investigate the epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin and fibrinolytic systems on plasma t-PA and PAI-1 levels in a large population-based sample (n=2,527). We demonstrated a strong significant interaction within genetic variations of the bradykinin B2 gene (p=0.002) and between ACE and bradykinin B2 (p=0.003) polymorphisms on t-PA levels in females. In males, polymorphisms in the bradykinin B2 and AT1R gene showed the most strong effect on t-PA levels (p=0.006). In both females as well as males, the bradykinin B2 gene interacted with AT1R gene on plasma PAI-1 levels (p=0.026 and p=0.039, respectively). In addition, the current study found a borderline significant interaction between PAI 4G5G and ACE I/D on plasma t-PA and PAI-1 levels. These results support the idea that the interplay between the renin-angiotensin, bradykinin, and fibrinolytic systems might play an important role in t-PA and PAI-1 biology. PMID:17207964

  13. Association studies suggest a key role for endothelin-1 in the pathogenesis of preeclampsia and the accompanying renin-angiotensin-aldosterone system suppression.

    Science.gov (United States)

    Verdonk, Koen; Saleh, Langeza; Lankhorst, Stephanie; Smilde, J E Ilse; van Ingen, Manon M; Garrelds, Ingrid M; Friesema, Edith C H; Russcher, Henk; van den Meiracker, Anton H; Visser, Willy; Danser, A H Jan

    2015-06-01

    Women with preeclampsia display low renin-angiotensin-aldosterone system activity and a high antiangiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase (sFlt)-1 and reduced placental growth factor levels. To investigate whether renin-angiotensin-aldosterone system suppression in preeclampsia is because of this disturbed angiogenic balance, we measured mean arterial pressure, creatinine, endothelin-1 (ET-1), and renin-angiotensin-aldosterone system components in pregnant women with a high (≥85; n=38) or low (<85; n=65) soluble Fms-like tyrosine kinase-1/placental growth factor ratio. Plasma ET-1 levels were increased in women with a high ratio, whereas their plasma renin activity and plasma concentrations of renin, angiotensinogen, and aldosterone were decreased. Plasma renin activity-aldosterone relationships were identical in both the groups. Multiple regression analysis revealed that plasma renin concentration correlated independently with mean arterial pressure and plasma ET-1. Plasma ET-1 correlated positively with soluble Fms-like tyrosine kinase-1 and negatively with plasma renin concentration, and urinary protein correlated with plasma ET-1 and mean arterial pressure. Despite the lower plasma levels of renin and angiotensinogen in the high-ratio group, their urinary levels of these components were elevated. Correction for albumin revealed that this was because of increased glomerular filtration. Subcutaneous arteries obtained from patients with preeclampsia displayed an enhanced, AT2 receptor-mediated response to angiotensin II. In conclusion, a high antiangiogenic state associates with ET-1 activation, which together with the increased mean arterial pressure may underlie the parallel reductions in renin and aldosterone in preeclampsia. Because ET-1 also was a major determinant of urinary protein, our data reveal a key role for ET-1 in the pathogenesis of preeclampsia. Finally, the enhanced angiotensin responsiveness

  14. Renin-angiotensin-aldosterone system inhibition: overview of the therapeutic use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and direct renin inhibitors.

    Science.gov (United States)

    Mercier, Kelly; Smith, Holly; Biederman, Jason

    2014-12-01

    Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy in hypertensive diabetic patients with macroalbuminuria, microalbuminuria, or normoalbuminuria has been repeatedly shown to improve cardiovascular mortality and reduce the decline in glomerular filtration rate. Renin-angiotensin-aldosterone system (RAAS) blockade in normotensive diabetic patients with normoalbuminuria or microalbuminuria cannot be advocated at present. Dual RAAS inhibition with ACE inhibitors plus ARBs or ACE inhibitors plus direct renin inhibitors has failed to improve cardiovascular or renal outcomes but has predisposed patients to serious adverse events. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. [The renin-angiotensin system and the sympathetic nervous system in essential hypertension].

    Science.gov (United States)

    Vincent, M; Milon, H; Revol, T; Annat, G; Froment, A; Sassard, J; Cier, J F

    1982-06-01

    In 112 patients with essential hypertension (HTA), free of any therapeutic and receiving the standard ward, a significant inverse relationship was found between age and plasma renin activity (PRA) and plasma aldosterone (PA), measured in the supine and upright position. Urinary epinephrine and norepinephrine were not related with age. When dividing the patients in 4 different age groups, it appeared that those younger than 30 years exhibited a significantly higher PRA and PA values and a higher frequency of borderline hypertension (45 p. 100) than the older ones (12 p. 100). So as to determine the characteristics associated with borderline HTA, it was necessary to eliminate the influence of age. This was achieved by comparing two groups of carefully age-matched patients, one with borderline HTA and the other with stable HTA. The only significant difference found was a significantly more marked increase in PRA in response to orthostatism, in patients with borderline HTA. Since renin responses to an orthostatic stress are largely mediated by renal nerves, this result suggest that borderline HTA could be associated with an increased reactivity of the sympathetic nervous system.

  16. Effects of aerobic exercise training on cardiac renin-angiotensin system in an obese Zucker rat strain.

    Directory of Open Access Journals (Sweden)

    Diego Lopes Mendes Barretti

    Full Text Available OBJECTIVE: Obesity and renin angiotensin system (RAS hyperactivity are profoundly involved in cardiovascular diseases, however aerobic exercise training (EXT can prevent obesity and cardiac RAS activation. The study hypothesis was to investigate whether obesity and its association with EXT alter the systemic and cardiac RAS components in an obese Zucker rat strain. METHODS: THE RATS WERE DIVIDED INTO THE FOLLOWING GROUPS: Lean Zucker rats (LZR; lean Zucker rats plus EXT (LZR+EXT; obese Zucker rats (OZR and obese Zucker rats plus EXT (OZR+EXT. EXT consisted of 10 weeks of 60-min swimming sessions, 5 days/week. At the end of the training protocol heart rate (HR, systolic blood pressure (SBP, cardiac hypertrophy (CH and function, local and systemic components of RAS were evaluated. Also, systemic glucose, triglycerides, total cholesterol and its LDL and HDL fractions were measured. RESULTS: The resting HR decreased (∼12% for both LZR+EXT and OZR+EXT. However, only the LZR+EXT reached significance (p<0.05, while a tendency was found for OZR versus OZR+EXT (p = 0.07. In addition, exercise reduced (57% triglycerides and (61% LDL in the OZR+EXT. The systemic angiotensin I-converting enzyme (ACE activity did not differ regardless of obesity and EXT, however, the OZR and OZR+EXT showed (66% and (42%, respectively, less angiotensin II (Ang II plasma concentration when compared with LZR. Furthermore, the results showed that EXT in the OZR prevented increase in CH, cardiac ACE activity, Ang II and AT2 receptor caused by obesity. In addition, exercise augmented cardiac ACE2 in both training groups. CONCLUSION: Despite the unchanged ACE and lower systemic Ang II levels in obesity, the cardiac RAS was increased in OZR and EXT in obese Zucker rats reduced some of the cardiac RAS components and prevented obesity-related CH. These results show that EXT prevented the heart RAS hyperactivity and cardiac maladaptive morphological alterations in obese Zucker rats.

  17. Effect of Uric Acid Lowering on Renin-Angiotensin-System Activation and Ambulatory BP: A Randomized Controlled Trial.

    Science.gov (United States)

    McMullan, Ciaran J; Borgi, Lea; Fisher, Naomi; Curhan, Gary; Forman, John

    2017-05-08

    Higher serum uric acid levels, even within the reference range, are strongly associated with increased activity of the renin-angiotensin system (RAS) and risk of incident hypertension. However, the effect of lowering serum uric acid on RAS activity in humans is unknown, although the data that lowering serum uric acid can reduce BP are conflicting. In a double-blind placebo-controlled trial conducted from 2011 to 2015, we randomly assigned 149 overweight or obese adults with serum uric acid ≥5.0 mg/dl to uric acid lowering with either probenecid or allopurinol, or to placebo. The primary endpoints were kidney-specific and systemic RAS activity. Secondary endpoints included mean 24-hour systolic BP, mean awake and asleep BP, and nocturnal dipping. Allopurinol and probenecid markedly lowered serum uric acid after 4 and 8 weeks compared with placebo (mean serum uric acid in allopurinol, probenecid, and placebo at 8 weeks was 2.9, 3.5, and 5.6 mg/dl, respectively). The change in kidney-specific RAS activity, measured as change in the median (interquartile range) renal plasma flow response to captopril (in ml/min per 1.73 m 2 ) from baseline to 8 weeks, was -4 (-25 to 32) in the probenecid group ( P =0.83), -4 (-16 to 9) in the allopurinol group ( P =0.32), and 1 (-21 to 17) in the placebo group ( P =0.96), with no significant treatment effect ( P =0.77). Similarly, plasma renin activity and plasma angiotensin II levels did not significantly change with treatment. The change in mean (±SD) 24-hour systolic BPs from baseline to 8 weeks was -1.6±10.1 with probenecid ( P =0.43), -0.4±6.1 with allopurinol ( P =0.76), and 0.5±6.0 with placebo ( P =0.65); there was no significant treatment effect ( P =0.58). Adverse events occurred in 9%, 12%, and 2% of those given probenecid, allopurinol, or placebo, respectively. In contrast to animal experiments and observational studies, this randomized, placebo-controlled trial found that uric acid lowering had no effect on kidney

  18. Acute kidney injury secondary to a combination of renin-angiotensin system inhibitors, diuretics and NSAIDS: "The Triple Whammy".

    Science.gov (United States)

    Camin, Rosa Maria Garcia; Cols, Montse; Chevarria, Julio Leonel; Osuna, Rosa García; Carreras, Marc; Lisbona, Josep Maria; Coderch, Jordi

    2015-01-01

    Renin-angiotensin system inhibitors (ACEI/ARB-II), diuretics and NSAIDs, a combination known as "Triple Whammy", can result in decreased glomerular filtration rate (GFR) and acute kidney injury (AKI). Objectives: To describe the incidence of AKI for each drug type and their combinations. To define the profile of patients admitted for drug-related AKI secondary to Triple Whammy drugs (AKITW), with an assessment of costs and mortality. A retrospective observational 15-month study developed in three stages: - First: a cross-sectional stage to identify and describe hospitalizations due to AKITW. - Second: a follow-up stage of an outpatient cohort consuming these drugs (15,307 subjects). - Third: a cohort stage to assess costs and mortality, which compared 62 hospitalized patients with AKITW and 62 without AKI, paired by medical specialty, sex, age and comorbidity according to their Clinical Risk Groups. There were 85 hospitalization episodes due to AKITW, and 78% of patients were over the age of 70. The incidence of AKITW in the population was 3.40 cases/1000 users/year (95% CI: 2.59-4.45). By categories, these were: NSAIDs + diuretics 8.99 (95% CI: 3.16-25.3); Triple Whammy 8.82 (95% CI: 4.4-17.3); ACEI/ARB-II + diuretics 6.87 (95% CI: 4.81-9.82); and monotherapy with diuretics 3.31 (95% CI: 1.39-7.85). Mean hospital stay was 7.6 days (SD 6.4), and mean avoidable costs were estimated at €214,604/100,000 inhabitants/year. Mortality during hospitalization and at 12 months was 11.3% and 38.7% respectively, and there were no significant differences when compared with the control group. Treatment with ACEI, ARB-II, diuretics and/or NSAIDs shows a high incidence of hospitalization episodes due to AKI; diuretics as monotherapy or dual and triple combination therapy cause the highest incidence. AKITW involves high health care costs and avoidable mortality. Copyright © 2015. Published by Elsevier España, S.L.U.

  19. Impact of The Protective Renin-Angiotensin System (RAS) on The Vasoreparative Function of CD34+ CACs in Diabetic Retinopathy

    Science.gov (United States)

    Duan, Yaqian; Moldovan, Leni; Miller, Rehae C.; Beli, Eleni; Salazar, Tatiana; Hazra, Sugata; Al-Sabah, Jude; Chalam, KV; Raghunandan, Sneha; Vyas, Ruchi; hide

    2016-01-01

    Purpose: In diabetes, the impaired vasoreparative function of Circulating Angiogenic Cells (CACs) is believed to contribute to the progression of diabetic retinopathy (DR). Accumulating evidence suggests that the protective arm of renin-angiotensin system (RAS) ACE2 Angiotensin-(1-7) Mas plays an important role in restoring the function of diabetic CACs. We examined the protective RAS in CACs in diabetic individuals with different stages of retinopathy. Methods: Study subjects (n43) were recruited as controls or diabetics with either no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR or proliferative DR (PDR). Fundus photography and fluorescein angiograms were analyzed using Vessel Generation Analysis (VESGEN) software in a cohort of subjects. CD34+ CACs were isolated from peripheral blood of diabetics and control subjects. RAS gene expressions in CACs were measured by qPCR. The vasoreparative function of CACs was assessed by migration ability toward CXCL12 using the QCM 5M 96-well chemotaxis cell migration assay. Results: ACE2 gene is a key enzyme converting the deleterious Angiotensin II to the beneficial Angiotensin-(1-7). ACE2 expression in CACs from diabetic subjects without DR was increased compared to controls, suggestive of compensation (p0.0437). The expression of Mas (Angiotensin-(1-7) receptor) in CACs was also increased in diabetics without DR, while was reduced in NPDR compared to controls (p0.0002), indicating a possible loss of compensation of the protective RAS at this stage of DR. The presence of even mild NPDR was associated with CD34+ CAC migratory dysfunction. When pretreating CACs of DR subjects with Angiotensin-(1-7), migratory ability to a chemoattractant CXCL12 was restored (p0.0008). By VESGEN analysis, an increase in small vessel density was observed in NPDR subjects when compared with the controls. Conclusions: These data suggest the protective RAS axis within diabetic CACs may help maintain their vasoreparative potential

  20. Plasma Molecular Signatures in Hypertensive Patients With Renin-Angiotensin System Suppression: New Predictors of Renal Damage and De Novo Albuminuria Indicators.

    Science.gov (United States)

    Baldan-Martin, Montserrat; Mourino-Alvarez, Laura; Gonzalez-Calero, Laura; Moreno-Luna, Rafael; Sastre-Oliva, Tamara; Ruiz-Hurtado, Gema; Segura, Julian; Lopez, Juan Antonio; Vazquez, Jesus; Vivanco, Fernando; Alvarez-Llamas, Gloria; Ruilope, Luis M; de la Cuesta, Fernando; Barderas, Maria G

    2016-07-01

    Albuminuria is a risk factor strongly associated with cardiovascular disease, the first cause of death in the general population. It is well established that renin-angiotensin system suppressors prevent the development of new-onset albuminuria in naïf hypertensive patients and diminish its excretion, but we cannot forget the percentage of hypertensive patients who develop de novo albuminuria. Here, we applied multiple proteomic strategy with the purpose to elucidate specific molecular pathways involved in the pathogenesis and provide predictors and chronic organ damage indicators. Briefly, 1143 patients were followed up for a minimum period of 3 years. One hundred and twenty-nine hypertensive patients chronically renin-angiotensin system suppressed were recruited, classified in 3 different groups depending on their albuminuria levels (normoalbuminuria, de novo albuminuria, and sustained albuminuria), and investigated by multiple proteomic strategies. Our strategy allowed us to perform one of the deepest plasma proteomic analysis to date, which has shown 2 proteomic signatures: (1) with predictive value of de novo albuminuria and (2) sustained albuminuria indicator proteins. These proteins are involved in inflammation, immune as well as in the proteasome activation occurring in situations of endoplasmic reticulum stress. Furthermore, these results open the possibility of a future strategy based on anti-immune therapy to treat hypertension which could help to prevent the development of albuminuria and, hence, the progression of kidney damage. © 2016 American Heart Association, Inc.

  1. The renin-angiotensin-aldosterone system (RAAS – physiology and molecular mechanisms of functioning

    Directory of Open Access Journals (Sweden)

    Monika Chaszczewska-Markowska

    2016-09-01

    Full Text Available Secretion of renin juxtaglomerular cells into bloodstream initiates activation of an enzymatic-hormonal cascade known as the RAAS (renin – angiotensin – aldosterone system. As a result, blood pressure is increased by the means several interrelated mechanisms. Mechanism of Zjednoczoaction of this system has been known for decades, but a few previously unknown components were recently added, such as ACE-2 and Ang(1-7, and their role often seems to be opposite to that of the conventional components. Local tissue systems also have important biological functions. They operate largely independently of the systemic activity, and their activity is observed primarily in the kidney, heart, in blood vessels, adrenal gland and nervous system. Angiotensin-2 (Ang-2, the main RAAS effector, has a wide scope of action, and thus abnormalities in its functioning have many consequences. Excessive activation is accompanied by chronic inflammation, as Ang-2 stimulates inflammatory mediators. As a result, degenerative processes and atherosclerosis are initiated. RAAS imbalance is associated with the most common diseases of civilization, such as cardio-vascular diseases, diabetes, kidney diseases, preeclampsia, osteoporosis and even neurodegenerative diseases. Many of these pathological processes are attributed to the excessive activation of tissue RA system. Therapeutic strategies based on inhibition of the RAAS are commonly used mainly in the treatment of hypertension and other cardiovascular disorders. The benefits of this class of drugs is primarily a decrease in blood pressure, but also the suppression of inflammatory processes and other pathological phenomena resulting from excessive activation of the RAAS. For that reason, some consider to use RAAS inhibitors in other diseases, e.g. Parkinson’s disease. Further studies give hope for the improvement of RAAS inhibitor therapy and the development of new therapeutic strategies

  2. The Renin-Angiotensin system in Hypertension and Diabetes: from man to rodent and back

    NARCIS (Netherlands)

    L.C.W. Roksnoer (Lodi)

    2016-01-01

    markdownabstractAbstract In addition to the systemic (endocrine) RAS, it is generally believed that the kidney has its own (paracrine) RAS, since it is capable of local angiotensin II synthesis, and all RAS components are expressed locally. Another source of RAS components in the kidney may be

  3. Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin-angiotensin-aldosterone system

    DEFF Research Database (Denmark)

    Aachmann-Andersen, Niels J.; Christensen, Soren J.; Lisbjerg, Kristian

    2018-01-01

    The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt...... intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance). rhEPO increased arterial blood pressure, total peripheral resistance...... of renin and aldosterone, independent of changes in red blood cell mass, blood volumes, and blood pressure. We also found changes in biomarkers showing evidence that rhEPO induced a prothrombotic state. Our results suggest that rhEPO causes a direct downregulation in proximal tubular reabsorption...

  4. Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY) : Essential study design and rationale of a randomised clinical multicentre trial

    NARCIS (Netherlands)

    Lindhardt, Morten; Persson, Frederik; Currie, Gemma; Pontillo, Claudia; Beige, Joachim; Delles, Christian; von der Leyen, Heiko; Mischak, Harald; Navis, Gerjan; Noutsou, Marina; Ortiz, Alberto; Ruggenenti, Piero Luigi; Rychlik, Ivan; Spasovski, Goce; Rossing, Peter

    2016-01-01

    Introduction Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment in

  5. Human in vivo study of the renin-angiotensin-aldosterone system and the sympathetic activity after 8 weeks daily intake of fermented milk

    DEFF Research Database (Denmark)

    Usinger, Lotte; Ibsen, Hans; Linneberg, Allan

    2010-01-01

    OBJECTIVE: Milk fermented by lactic acid bacteria is suggested to have antihypertensive effect in humans. In vitro and animal studies have established an angiotensin-converting enzyme (ACE) inhibitor effect of peptides in fermented milk. However, other modes of action must be considered, because...... until today no human studies have confirmed an ACE inhibition in relation to the intake of fermented milk. MATERIALS AND METHODS: We undertook a double-blinded randomized placebo-controlled study including 94 borderline-hypertensive persons to study the effect on human physiology of Lactobacillus...... helveticus fermented milk. The subjects were randomized into three groups: Cardi04-300 ml, Cardi04-150 ml or placebo. All components of the renin-angiotensin-aldosterone system were measured several times. Sympathetic activity was estimated by plasma noradrenaline and cardiovascular response to head-up tilt...

  6. Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity

    DEFF Research Database (Denmark)

    Høi-Hansen, Thomas; Pedersen-Bjergaard, Ulrik; Andersen, Rikke Due

    2009-01-01

    potentials and hypoglycaemic symptoms were recorded. RESULTS: At a hypoglycaemic nadir of 2.2 (SD 0.3) mmol/L the high RAS group displayed significant deterioration in cognitive performance during hypoglycaemia in the three most complex reaction time tasks. In the low RAS group, hypoglycaemia led......INTRODUCTION: High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patients...... with low RAS activity. MATERIALS AND METHODS: Nine patients with type 1 diabetes and high and nine with low RAS activity were subjected to hypoglycaemia and euglycaemia in a cross-over study using an intravenous insulin infusion protocol. Cognitive function, electroencephalography, auditory evoked...

  7. Human in vivo study of the renin-angiotensin-aldosterone system and the sympathetic activity after 8 weeks daily intake of fermented milk.

    Science.gov (United States)

    Usinger, Lotte; Ibsen, Hans; Linneberg, Allan; Azizi, Michel; Flambard, Bénédicte; Jensen, Lars T

    2010-03-01

    Milk fermented by lactic acid bacteria is suggested to have antihypertensive effect in humans. In vitro and animal studies have established an angiotensin-converting enzyme (ACE) inhibitor effect of peptides in fermented milk. However, other modes of action must be considered, because until today no human studies have confirmed an ACE inhibition in relation to the intake of fermented milk. We undertook a double-blinded randomized placebo-controlled study including 94 borderline-hypertensive persons to study the effect on human physiology of Lactobacillus helveticus fermented milk. The subjects were randomized into three groups: Cardi04-300 ml, Cardi04-150 ml or placebo. All components of the renin-angiotensin-aldosterone system were measured several times. Sympathetic activity was estimated by plasma noradrenaline and cardiovascular response to head-up tilt at baseline and after 8 weeks of intervention. No ACE inhibition of the fermented milk was demonstrated, as none of the components of the renin-angiotensin-aldosteron system changed. Plasma noradrenaline response to tilt test after intervention stayed unchanged between groups (P = 0.38), but declined in the group Cardi04-300 from 2.01 +/- 0.93 nmol l(-1) at baseline to 1.49 +/- 0.74 nmol l(-1) after 8 weeks (P = 0.002). There was no change in 24-h ambulatory blood pressure or heart rate between groups. Despite a known ACE inhibitory effect in vitro and in animals, milk fermented with Lb. helveticus did not inhibit ACE in humans. Our results suggest that the intake of fermented milk decreases sympathetic activity, although not to an extent mediating reductions of blood pressure and heart rate in borderline-hypertensive subjects.

  8. Potential impact of renin-angiotensin system inhibitors and calcium channel blockers on plasma high-molecular-weight adiponectin levels in hemodialysis patients

    International Nuclear Information System (INIS)

    Nakagawa, Naoki; Yao, Naoyuki; Hirayama, Tomoya

    2011-01-01

    Although metabolic syndrome confers an increased risk of cardiovascular disease in the general population, little is known about the alteration of abdominal adiposity and its association with adipocytokines in hemodialysis patients. We investigated the plasma high-molecular-weight (HMW) adiponectin level and its relationship to visceral fat area (VFA) and various markers of atherosclerosis in hemodialysis patients. In a cross-sectional study, conventional cardiovascular risk factors, plasma total and HMW adiponectin, the number of components of the metabolic syndrome and, using computed tomography, the distribution of abdominal adiposity were assessed in 144 hemodialysis patients (90 men and 54 women; mean age, 60.7 years) and 30 age- and sex-matched patients with chronic kidney disease (CKD). Plasma HMW adiponectin levels in hemodialysis patients were significantly higher than those in patients with CKD, negatively associated with VFA and serum triglycerides and positively associated with plasma total adiponectin, as well as the HMW-to-total adiponectin ratio in men and women (all P<0.05) in a simple regression analysis. In a multiple regression analysis, VFA was a significant determinant of HMW adiponectin in hemodialysis patients. Furthermore, after adjustment for classical risk factors, HMW adiponectin levels were significantly higher in patients undergoing treatment with renin-angiotensin system inhibitors or calcium channel blockers compared with patients not undergoing such treatment. This study shows that plasma HMW adiponectin levels were negatively associated with VFA and positively associated with treatment with blockade of the renin-angiotensin system and of the calcium channel. Therefore, these drugs might be effective for improving adipocytokine-related metabolic abnormalities in hemodialysis patients. (author)

  9. Upregulation of the Renin-Angiotensin-Aldosterone-Ouabain System in the Brain Is the Core Mechanism in the Genesis of All Types of Hypertension

    Directory of Open Access Journals (Sweden)

    Hakuo Takahashi

    2012-01-01

    Full Text Available Basic research using animal models points to a causal role of the central nervous system in essential hypertension; however, since clinical research is technically difficult to perform, this connection has not been confirmed in humans. Recently, renal nerve ablation in humans proved to continuously decrease blood pressure in resistant hypertension. Furthermore, when electrical stimulation was continuously applied to the carotid baroreceptor nerve of human adults, their blood pressure lowered. These findings promoted the concept that the central nervous system may actually be involved in the pathogenesis of essential hypertension, which is closely associated with excess sodium intake. We have demonstrated that endogenous digitalis plays a key role in hypertension associated with excess sodium intake via sympathetic activation in rats. Increased sodium concentration inside the brain activates epithelial sodium channels and the renin-angiotensin-aldosterone system in the brain. Aldosterone releases ouabain from neurons in the paraventricular nucleus in the hypothalamus. Angiotensin II and aldosterone of peripheral origin reach the brain to augment sympathetic outflow. Collectively essential hypertension associated with excess sodium intake and obesity, renovascular hypertension, and primary aldosteronism and pseudoaldosteronism all seem to have a common cause originating from the central nervous system.

  10. Effect of ipsilateral ureteric obstruction on contralateral kidney and role of renin angiotensin system blockade on renal recovery in experimentally induced unilateral ureteric obstruction

    Directory of Open Access Journals (Sweden)

    Shasanka S Panda

    2013-01-01

    Full Text Available Aims: To study, the effects of ipsilateral ureteric obstruction on contralateral kidney and the role of renin angiotensin system (RAS blockade on renal recovery in experimentally induced unilateral ureteric obstruction. Materials and Methods: Unilateral upper ureteric obstruction was created in 96 adult Wistar rats that were reversed after pre-determined intervals. Losartan and Enalapril were given to different subgroups of rats following relief of obstruction. Results: The severity of dilatation on the contralateral kidney varied with duration of ipsilateral obstruction longer the duration more severe the dilatation. There is direct correlation between renal parenchymal damage, pelvi-ureteric junction (PUJ fibrosis, inflammation and severity of pelvi-calyceal system dilatation of contralateral kidney with duration of ipsilateral PUJ obstruction. Conclusions: Considerable injury is also inflicted to the contralateral normal kidney while ipsilateral kidney remains obstructed. Use of RAS blocking drugs has been found to significantly improve renal recovery on the contralateral kidney. It can, thus, be postulated that contralateral renal parenchymal injury was mediated through activation of RAS.

  11. Interactive effects of apelin, renin-angiotensin system and nitric oxide in treatment of obesity-induced type 2 diabetes mellitus in male albino rats.

    Science.gov (United States)

    Sabry, Maha Mohamed; Mahmoud, Manal Moustafa; Shoukry, Heba Samy; Rashed, Laila; Kamar, Samaa Samir; Ahmed, Mona Mohamed

    2018-03-22

    Apelin and its receptor (APJ) are involved in the regulation of a variety of pathophysiological processes. We studied the effect of apelin treatment on obesity-induced type 2 diabetes mellitus (T2DM) and possible interaction between apelin/APJ system and renin-angiotensin system (RAS). Forty eight male albino rats were divided into two groups: control group and diabetic group. Diabetic group was subdivided into: control diabetic, apelin-treated, apelin + losartan-treated, apelin + l-NAME-treated and losartan-treated diabetic subgroup. Administration of apelin-13 yielded an improvement of IR, dyslipidaemia, inflammation, oxidative stress with significant decrease in AT1R gene expression and significant increase in ACE2 gene expression in adipose tissues. Losartan + apelin yielded a further significant decrease in ATR1 gene expression, glycaemic indices, serum TGs and TPA versus Apelin only. Adding l-NAME in subgroup (2D) reversed the effect of apelin. We suggested that the beneficial effect of Apelin is mainly mediated by NO-activated pathway and/or ACE2/Ang (1-7) dependent pathway.

  12. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

    Science.gov (United States)

    Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

    2015-01-01

    Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1–7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1–7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation. PMID:26569234

  13. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

    Directory of Open Access Journals (Sweden)

    Guoxing Wang

    2015-11-01

    Full Text Available Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg group. Thirty min after drug infusion, ventricular fibrillation (8 min and cardiopulmonary resuscitation (up to 30 min was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II and Ang (1–7 levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE, ACE2, Ang II type 1 receptor (AT1R, and the Ang (1–7 receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS, cyclic guanosine monophosphate (cGMP and inducible nitric oxide synthase(iNOS. Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

  14. Effects of aqueous extract of Hibiscus sabdariffa on the renin-angiotensin-aldosterone system of Nigerians with mild to moderate essential hypertension: A comparative study with lisinopril.

    Science.gov (United States)

    Nwachukwu, Daniel Chukwu; Aneke, Eddy Ikemefuna; Obika, Leonard Fidelis; Nwachukwu, Nkiru Zuada

    2015-01-01

    The present study investigated the effects of aqueous extract of Hibiscus sabdariffa (HS) on the three basic components of renin-angiotensin-aldosterone system: Plasma renin, serum angiotensin-converting enzyme (ACE), and plasma aldosterone (PA) in mild to moderate essential hypertensive Nigerians and compared with that of lisinopril, an ACE inhibitor. A double-blind controlled randomized clinical study was used. Seventy-eight newly diagnosed but untreated mild to moderate hypertensive subjects attending Medical Outpatients Clinic of Enugu State University Teaching Hospital, Enugu were recruited for the study. Those in Group A received placebo (150 mg/kg/day), Group B were given lisinopril (10 mg once daily) while those in Group C received aqueous extract of HS (150 mg/kg/day). After 4 weeks of treatment, the levels of plasma renin, serum ACE, and PA were determined. HS and lisinopril significantly (P < 0.001) reduced PA compared to placebo by 32.06% and 30.01%, respectively. Their effects on serum ACE and plasma renin activity (PRA) were not significant compared to placebo; they reduced ACE by 6.63% and 5.67% but increased plasma PRA by 2.77% and 5.36%, respectively. HS reduced serum ACE and PA in mild to moderate hypertensive Nigerians with equal efficacy as lisinopril. These actions are possibly due to the presence of anthocyanins in the extract.

  15. Prenatal inflammation-induced NF-κB dyshomeostasis contributes to renin-angiotensin system over-activity resulting in prenatally programmed hypertension in offspring

    Science.gov (United States)

    Deng, Youcai; Deng, Yafei; He, Xiaoyan; Chu, Jianhong; Zhou, Jianzhi; Zhang, Qi; Guo, Wei; Huang, Pei; Guan, Xiao; Tang, Yuan; Wei, Yanling; Zhao, Shanyu; Zhang, Xingxing; Wei, Chiming; Namaka, Michael; Yi, Ping; Yu, Jianhua; Li, Xiaohui

    2016-01-01

    Studies involving the use of prenatally programmed hypertension have been shown to potentially contribute to prevention of essential hypertension (EH). Our previous research has demonstrated that prenatal inflammatory stimulation leads to offspring’s aortic dysfunction and hypertension in pregnant Sprague-Dawley rats challenged with lipopolysaccharide (LPS). The present study found that prenatal LPS exposure led to NF-κB dyshomeostasis from fetus to adult, which was characterized by PI3K-Akt activation mediated degradation of IκBα protein and impaired NF-κB self-negative feedback loop mediated less newly synthesis of IκBα mRNA in thoracic aortas (gestational day 20, postnatal week 7 and 16). Prenatal or postnatal exposure of the IκBα degradation inhibitor, pyrollidine dithiocarbamate, effectively blocked NF-κB activation, endothelium dysfunction, and renin-angiotensin system (RAS) over-activity in thoracic aortas, resulting in reduced blood pressure in offspring that received prenatal exposure to LPS. Surprisingly, NF-κB dyshomeostasis and RAS over-activity were only found in thoracic aortas but not in superior mesenteric arteries. Collectively, our data demonstrate that the early life NF-κB dyshomeostasis induced by prenatal inflammatory exposure plays an essential role in the development of EH through triggering RAS over-activity. We conclude that early life NF-κB dyshomeostasis is a key predictor of EH, and thus, NF-κB inhibition represents an effective interventional strategy for EH prevention. PMID:26877256

  16. Effect of L-5-Hydroxytryptophan on drinking behavior in Coturnix japonica (Temminck and Schlegel, 1849 (Galliformes: Aves: involvement of renin-angiotensin system

    Directory of Open Access Journals (Sweden)

    PL Cedraz-Mercez

    Full Text Available The purpose of this study was to explore the role of L-5-hydroxytryptophan (L-HTP and its relationship with the renin-angiotensin system (RAS on the drinking behavior in Japanese quails. Normally-hydrated quails that received injections of L-HTP (12.5; 25 and 50 mg.kg-1 by the intracoelomic route (ic expressed an increase in water intake, which was inhibited by captopril, an angiotensin converting enzyme (ACE inhibitor. In addition, captopril also induced such a response in birds under previous fluid deprivation. High doses of captopril (35-70 mg.kg-1, sc in normally-hydrated quails decreased the spontaneous water intake while low doses of captopril (2-5 mg.kg-1, sc did not prompt water intake after L-HTP administration. Losartan, an AT1 receptor antagonist in mammals, did not change the water intake levels in normally-hydrated or water-deprivated birds. Serotonin (5-HT injections did not provoke its known dipsogenic response.

  17. Prenatal inflammation-induced NF-κB dyshomeostasis contributes to renin-angiotensin system over-activity resulting in prenatally programmed hypertension in offspring.

    Science.gov (United States)

    Deng, Youcai; Deng, Yafei; He, Xiaoyan; Chu, Jianhong; Zhou, Jianzhi; Zhang, Qi; Guo, Wei; Huang, Pei; Guan, Xiao; Tang, Yuan; Wei, Yanling; Zhao, Shanyu; Zhang, Xingxing; Wei, Chiming; Namaka, Michael; Yi, Ping; Yu, Jianhua; Li, Xiaohui

    2016-02-15

    Studies involving the use of prenatally programmed hypertension have been shown to potentially contribute to prevention of essential hypertension (EH). Our previous research has demonstrated that prenatal inflammatory stimulation leads to offspring's aortic dysfunction and hypertension in pregnant Sprague-Dawley rats challenged with lipopolysaccharide (LPS). The present study found that prenatal LPS exposure led to NF-κB dyshomeostasis from fetus to adult, which was characterized by PI3K-Akt activation mediated degradation of IκBα protein and impaired NF-κB self-negative feedback loop mediated less newly synthesis of IκBα mRNA in thoracic aortas (gestational day 20, postnatal week 7 and 16). Prenatal or postnatal exposure of the IκBα degradation inhibitor, pyrollidine dithiocarbamate, effectively blocked NF-κB activation, endothelium dysfunction, and renin-angiotensin system (RAS) over-activity in thoracic aortas, resulting in reduced blood pressure in offspring that received prenatal exposure to LPS. Surprisingly, NF-κB dyshomeostasis and RAS over-activity were only found in thoracic aortas but not in superior mesenteric arteries. Collectively, our data demonstrate that the early life NF-κB dyshomeostasis induced by prenatal inflammatory exposure plays an essential role in the development of EH through triggering RAS over-activity. We conclude that early life NF-κB dyshomeostasis is a key predictor of EH, and thus, NF-κB inhibition represents an effective interventional strategy for EH prevention.

  18. Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity.

    Science.gov (United States)

    Høi-Hansen, Thomas; Pedersen-Bjergaard, Ulrik; Andersen, Rikke Due; Kristensen, Peter Lommer; Thomsen, Carsten; Kjaer, Troels; Høgenhaven, Hans; Smed, Annelise; Holst, Jens Juul; Dela, Flemming; Boomsma, Frans; Thorsteinsson, Birger

    2009-12-01

    High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patients with low RAS activity. Nine patients with type 1 diabetes and high and nine with low RAS activity were subjected to hypoglycaemia and euglycaemia in a cross-over study using an intravenous insulin infusion protocol. Cognitive function, electroencephalography, auditory evoked potentials and hypoglycaemic symptoms were recorded. At a hypoglycaemic nadir of 2.2 (SD 0.3) mmol/L the high RAS group displayed significant deterioration in cognitive performance during hypoglycaemia in the three most complex reaction time tasks. In the low RAS group, hypoglycaemia led to cognitive dysfunction in only one reaction time task. The high RAS group reported lower symptom scores during hypoglycaemia than the low RAS group, suggesting poorer hypoglycaemia awareness. High RAS activity is associated with increased cognitive dysfunction and blunted symptoms during mild hypoglycaemia compared to low RAS activity. This may explain why high RAS activity is a risk factor for severe hypoglycaemia in type 1 diabetes.

  19. MITOCHONDRIAL REACTIVE OXYGEN SPECIES (ROS AS SIGNALLING MOLECULES OF INTRACELLULAR PATHWAYS TRIGGERED BY THE CARDIAC RENIN-ANGIOTENSIN II-ALDOSTERONE SYSTEM (RAAS.

    Directory of Open Access Journals (Sweden)

    Verónica Celeste De Giusti

    2013-05-01

    Full Text Available Mitochondria represent major sources of basal reactive oxygen species (ROS production of the cardiomyocyte. The role of ROS as signalling molecules that mediate different intracellular pathways has gained increasing interest among physiologists in the last years. In our lab, we have been studying the participation of mitochondrial ROS in the intracellular pathways triggered by the renin-angiotensin II-aldosterone system (RAAS in the myocardium during the past few years. We have demonstrated that acute activation of cardiac RAAS induces mitochondrial ATP-dependent potassium channel (mitoKATP opening with the consequent enhanced production of mitochondrial ROS. These oxidant molecules, in turn, activate membrane transporters, as sodium/hydrogen exchanger (NHE-1 and sodium/bicarbonate cotransporter (NBC via the stimulation of the ROS-sensitive MAPK cascade. The stimulation of such effectors leads to an increase in cardiac contractility. In addition, it is feasible to suggest that a sustained enhanced production of mitochondrial ROS induced by chronic cardiac RAAS, and hence, chronic NHE-1 and NBC stimulation, would also result in the development of cardiac hypertrophy.

  20. Prognostic Impact of Loop Diuretics in Patients With Chronic Heart Failure - Effects of Addition of Renin-Angiotensin-Aldosterone System Inhibitors and β-Blockers.

    Science.gov (United States)

    Miura, Masanobu; Sugimura, Koichiro; Sakata, Yasuhiko; Miyata, Satoshi; Tadaki, Soichiro; Yamauchi, Takeshi; Onose, Takeo; Tsuji, Kanako; Abe, Ruri; Oikawa, Takuya; Kasahara, Shintaro; Nochioka, Kotaro; Takahashi, Jun; Shimokawa, Hiroaki

    2016-05-25

    It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients. From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (Pdiuretics were associated with worse prognosis with HR 1.32 and 1.56, respectively (both Pdiuretics. Chronic use of loop diuretics is significantly associated with worse prognosis in CHF patients in a dose-dependent manner, whereas the triple combination of RAAS inhibitor(s), MRA, and β-blocker(s) is associated with better prognosis when combined with low-dose loop diuretics. (Circ J 2016; 80: 1396-1403).

  1. Paradoxic activation of the renin-angiotensin system in twin-twin transfusion syndrome: an explanation for cardiovascular disturbances in the recipient.

    Science.gov (United States)

    Mahieu-Caputo, Dominique; Meulemans, Alain; Martinovic, Jelena; Gubler, Marie-Claire; Delezoide, Anne-Lise; Muller, Françoise; Madelenat, Patrick; Fisk, Nicholas M; Dommergues, Marc

    2005-10-01

    Despite advances in treatment, twin-to-twin transfusion syndrome (TTTS) still carries a high risk for perinatal mortality and morbidity. Simple blood transfer from the donor to the recipient twin cannot explain all of the features of this disease, in particular the recipient's hypertensive cardiomyopathy. We report a case in which TTTS resulted in preterm delivery with early neonatal death of both twins, allowing assessment of the renin angiotensin system (RAS) status of each fetus, both by cord blood renin and aldosterone assay and by renal immunohistochemistry. The donor had severe oliguria/oligohydramnios, whereas the recipient, in addition to severe polyuria/polyhydramnios, had cardiomyopathy, atrioventricular regurgitation, and ascites. Although immunohistochemistry demonstrated that renal secretion of renin was up-regulated in the donor and down-regulated in the recipient, cord blood levels of renin and aldosterone were similar, with high renin levels in both twins. This observation supports the hypothesis that despite renal RAS down-regulation, the recipient is exposed to RAS effectors elaborated in the donor and transferred via placental shunts. This may contribute to cardiomyopathy and hypertension in the recipient, which cannot be accounted for by hypervolemia alone. We thus hypothesized that in TTTS, the recipient's hypertensive cardiomyopathy could be due to a mechanism similar to the classical model of hypertension referred to as "2 kidneys-1 clip." Thus the hypovolemic donor twin, comparable to the clipped kidney, produces vasoactive hormones that compromise the recipient, comparable to the normal kidney, causing hypertension and cardiomyopathy.

  2. Association between renin-angiotensin-aldosterone system blockade and future osteoporotic fracture risk in hypertensive population: A population-based cohort study in Taiwan.

    Science.gov (United States)

    Chen, Chang-I; Yeh, Jong-Shiuan; Tsao, Nai-Wen; Lin, Fen-Yen; Shih, Chun-Ming; Chiang, Kuang-Hsing; Kao, Yung-Ta; Fang, Yu-Ann; Tsai, Lung-Wen; Liu, Wen-Chi; Nakagami, Hironori; Morishita, Ryuichi; Kuo, Yi-Jie; Huang, Chun-Yao

    2017-11-01

    Tissue renin-angiotensin-aldosterone system (RAAS) activation in sites of osteoporosis had been demonstrated in animal studies; however, the possibility of RAAS blockade to prevent future osteoporotic fracture had rarely been verified in clinical studies. We Used the Taiwan Longitudinal Health insurance database 2000 to 2008, the cohort study comprised patients age over 40 with a recorded new diagnosis of hypertension between January 1, 2000 to December 31, 2008, in addition, patients who had diagnosis of osteoporosis before the date of cohort enter were excluded. After the definite diagnosis of hypertension, each patient was followed until osteoporotic fracture happened or the end of 2008. The occurrence of osteoporotic fracture was evaluated in patients who either were or without taking RAAS blockade agents. Cox proportional hazard regressions were used to evaluate the osteoporotic fracture incidence after adjusting for known confounding factors. In total, 57,132 hypertensive patients comprised the study cohort. Our study results showed that the incidence of osteoporosis fracture in the whole cohort was significantly higher in the RAAS blockade non-user group than the user group. This phenomenon was observed in both sex and all age categories. Sensitivity analysis further showed the concordant lower osteoporosis fracture risk in patients with various RAAS blockers usage durations; the risk of osteoporosis fracture was the lowest in those drug use >365 days when compared with the non-user cohort. In conclusion, our study result demonstrated the lower future osteoporotic fracture risk in hypertensive subjects who received long term RAAS blocker treatment.

  3. Early renin-angiotensin system intervention is more beneficial than late intervention in delaying end-stage renal disease in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Schievink, B; Kröpelin, T; Mulder, S

    2016-01-01

    AIMS: To develop and validate a model to simulate progression of diabetic kidney disease (DKD) from early onset until end-stage renal disease (ESRD), and to assess the effect of renin-angiotensin system (RAS) intervention in early, intermediate and advanced stages of DKD. METHODS: We used data from......, intermediate and advanced stage of disease, whose mean age was 60 years and who received placebo, the median time to ESRD was 21.4, 10.8 and 4.7 years, respectively. RAS intervention delayed the predicted time to ESRD by 4.2, 3.6 and 1.4 years, respectively. The benefit of early RAS intervention was more...... pronounced in younger patients; for example, for patients with a mean age of 45 years, RAS intervention at early, intermediate or advanced stage delayed ESRD by 5.9, 4.0 and 1.1 years versus placebo. CONCLUSIONS: RAS intervention early in the course of proteinuric DKD is more beneficial than late...

  4. The Relationship Between the Renin-Angiotensin-Aldosterone System and NMDA Receptor-Mediated Signal and the Prevention of Retinal Ganglion Cell Death.

    Science.gov (United States)

    Kobayashi, Mamoru; Hirooka, Kazuyuki; Ono, Aoi; Nakano, Yuki; Nishiyama, Akira; Tsujikawa, Akitaka

    2017-03-01

    Excitotoxicity, which is due to glutamate-induced toxic effects on the retinal ganglion cell (RGC), is one of several mechanisms of RGC loss. The renin-angiotensin-aldosterone system (RAAS) has also been implicated in RGC death. Therefore, it is important to determine the exact relationship between the RAAS and N-methyl-d-aspartate (NMDA) receptor-mediated signal in order to prevent RGC death. N-methyl-d-aspartate or aldosterone was injected into the vitreous body. After intravitreal injection of NMDA or aldosterone, animals were treated with spironolactone or memantine. Retinal damage was evaluated by measuring the number of RGCs at 4 weeks after local administration of aldosterone or at 2 weeks after local administration of NMDA. Vitreous humor levels of aldosterone were measured using enzyme immunoassay kits. A significantly decreased number of RGCs were observed after intravitreal injection of NMDA. Although spironolactone did not show any neuroprotective effects, memantine significantly reduced NMDA-induced degeneration in the retina. Furthermore, a significant decrease in the number of RGCs was observed after an intravitreal injection of aldosterone. While memantine did not exhibit any neuroprotective effects, spironolactone caused a significant reduction in the aldosterone-induced degeneration in the retina. There was no change in the aldosterone concentration in the vitreous humor after an NMDA injection. Our findings indirectly show that there is no relationship between the RAAS and NMDA receptor-mediated signal with regard to RGC death.

  5. Long-Term Regulation of the Local Renin-Angiotensin System in the Myocardium of Spontaneously Hypertensive Rats by Feeding Bioactive Peptides Derived from Spirulina platensis.

    Science.gov (United States)

    Pan, Huanglei; She, Xingxing; Wu, Hongli; Ma, Jun; Ren, Difeng; Lu, Jun

    2015-09-09

    This study investigated the long-term (8 weeks) anti-hypertensive effects of 10 mg/kg tripeptides isolated from Spirulina platensis, Ile-Gln-Pro (IQP) and Val-Glu-Pro (VEP), and S. platensis hydrolysates (SH) on spontaneously hypertensive rats. The treatment period was 6 weeks, and observation continued for another 2 weeks. After treatment, weighted systolic blood pressure, weighted diastolic blood pressure, left ventricular mass index, and right ventricular mass index of groups treated with IQP, VEP, and SH were significantly lower than those of the group treated with distilled water, even when the treatments had been withdrawn for 2 weeks. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting showed the mRNA expression levels and protein/peptide concentrations of the main components of the renin angiotensin system in myocardium were significantly affected by treatment: angiotensin converting enzyme, angiotensin II, and angiotensin type 1 receptor were down-regulated, whereas angiotensin type 2 receptor, angiotensin converting enzyme 2, angiotensin-(1-7), and Mas receptor were up-regulated.

  6. Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat

    Directory of Open Access Journals (Sweden)

    Jian-Dong Li

    2016-01-01

    Full Text Available Heart failure (HF is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS activity and elevated levels of proinflammatory cytokines (PICs. Renal denervation (RD has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO- induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-α inhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD.

  7. Orthostatic effects of midodrine versus L-NAME on cerebral blood flow and the renin-angiotensin-aldosterone system in tetraplegia.

    Science.gov (United States)

    Wecht, Jill M; Radulovic, Miroslav; Rosado-Rivera, Dwindally; Zhang, Run-Lin; LaFountaine, Michael F; Bauman, William A

    2011-11-01

    To compare responses to head-up tilt (HUT) in individuals with chronic tetraplegia after midodrine hydrochloride (10 mg) versus nitro-L-arginine methyl ester (L-NAME, 1 mg/kg) administration. Prospective comparative drug trial. Veterans Affairs medical center. Participants (N=7) were studied during 3 laboratory visits: no drug, midodrine (administered orally 30 min before HUT), and L-NAME (infused over a 60-min period). Anti-hypotensive agents, midodrine, and L-NAME. Mean arterial pressure (MAP), cerebral blood flow (CBF), and markers of the renin-angiotensin-aldosterone system (RAAS, plasma renin and serum aldosterone) were measured in the supine position at baseline (BL) and during a 45° HUT maneuver. Data were compared between BL and the average of 3 assessments collected during HUT. Orthostatic MAP and CBF were increased with the midodrine and L-NAME groups compared with the no drug trial and the relationship between the change in MAP and CBF was significant (r=0.770; Pmidodrine appeared to suppress the post-HUT RAAS response compared with no drug. Increasing orthostatic blood pressure with L-NAME or midodrine appears to increase CBF and suppress the RAAS during HUT in persons with tetraplegia, although more data are needed to confirm these preliminary findings. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  8. [The in vitro cross-effects of inhibitors of renin-angiotensin and fibrinolytic systems on the key enzymes of these systems].

    Science.gov (United States)

    Mukhametova, L I; Gulin, D A; Binevskiĭ, P V; Aĭsina, R B; Kost, O A; Nikol'skaia, I I

    2008-01-01

    The effects of hypotensive agents (captopril, enalaprilate, and lisinopril) on the activities of components of the fibrinolytic system (FS) and the effects of antifibrinolytic agents (6-aminohexanoic acid (6-AHA) and tranexamic acid (t-AMCHA)) on the activities of angiotensin converting enzyme (ACE) were studied in vitro. Enalaprilate did not affect the FS activity. Captopril considerably inhibited the amidase activities of urokinase (u-PA), plasminogen tissue activator (t-PA), and plasmin ([I]50 (2.0-2.6) +/- 0.1 mM), and the activation of Glu-plasminogen affected by t-PA and u-PA ([I]50 (1.50-1.80) +/- 0.06 mM), which may be due to the presence of a mercapto group in the inhibitor molecule. Lisinopril did not affect the amidase activities of FS enzymes, but stimulated Glu-plasminogen and u-PA activation and inhibited activation of t-PA-fibrin-bound Glu-plasminogen ([I]50 (12.0 +/- 0.5) mM). Presumably, these effects can be explained by the presence in lisinopril of a Lys side residue, whose binding to lysine-binding Glu-plasminogen centers resulted, on the one hand, in the transformation of its closed conformation to a semi-open one and, on the other hand, in its desorption from fibrin. Unspecific inhibition of the activity of ACE, a key enzyme of the renin-angiotensin system, in the presence of 6-AHA and t-AMCHA ([I]50 10.0 +/- 0.5 and 7.5 +/- 0.4 mM, respectively) was found. A decrease in the ACE activity along with the growth of the fibrin monomer concentration was revealed. The data demonstrate that, along with endogenous mediated interactions, relations based on the direct interactions of exogenous inhibitors of one system affecting the activities of components of another system can take place.

  9. Addition of ETA receptor blockade increases renoprotection provided by renin-angiotensin system blockade in 5/6 nephrectomized Ren-2 transgenic rats

    Czech Academy of Sciences Publication Activity Database

    Čertíková; Chábová, V.; Vernerová, Z.; Kujal, P.; Husková, Z.; Škaroupková, P.; Tesař, V.; Kramer, H. J.; Kompanowska; Jezierska, E.; Walkowska, A.; Sadowski, J.; Červenka, L.; Vaněčková, Ivana

    2014-01-01

    Roč. 118, č. 2 (2014), s. 297-305 ISSN 0024-3205 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : renal failure * 5/6 nephrectomy * renin-angiotensin * endothelin * survival Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.702, year: 2014

  10. Quantification of systemic renin-angiotensin system peptides of hypertensive black and white African men established from the RAS-Fingerprint®

    Directory of Open Access Journals (Sweden)

    JM van Rooyen

    2016-10-01

    Full Text Available Objective: The objective of this study was to make use of a quantitative and qualitative approach comparing the systemic renin-angiotensin system (RAS of hypertensive black and white African men by using RAS equilibrium analysis. Materials and methods: This sub-study involved 23 black (n = 15 and white (n = 8 hypertensive men aged 39.5–41 years, living in the North West Province of South Africa. The RAS-Fingerprinting was determined with LC-MS/MS quantification of angiotensin peptides. Blood pressure and other variables were determined with known methods. Results: The main finding of this study was the significant lower Ang I (<5.0 and 45.1 pg/ml; p = 0.005 and Ang II (15.6 and 123.9 pg/ml; p ⩽ 0.001 encountered in the hypertensive black African men compared to their white counterparts. Levels of Ang 1-5 (downstream metabolite of Ang 1-7 (1.8 and 3.0 pg/ml, were detected in black and white hypertensive men, respectively. Conclusions: The observed differences between circulating RAS components, which are reflected via equilibrium angiotensin levels, point to a distinctive molecular regulation of the RAAS in the two study cohorts. The increased peripheral resistance observed in hypertensive black individuals might take over a dominant role in control of blood pressure in this study population. A novel highly sensitive LC-MS/MS method resolved the issue of peptide recovery variations during sample preparation by using internal standards for each individual angiotensin metabolite.

  11. Endothelin A receptor antagonism in experimental congestive heart failure results in augmentation of the renin-angiotensin system and sustained sodium retention.

    Science.gov (United States)

    Schirger, John A; Chen, Horng H; Jougasaki, Michihisa; Lisy, Ondrej; Boerrigter, Guido; Cataliotti, Alessandro; Burnett, John C

    2004-01-20

    While both the endothelin-1 (ET-1) and renin-angiotensin systems (RAS) are activated in congestive heart failure (CHF), the temporal sequence of this activation remains unclear. Understanding this pattern of neurohumoral activation may aid in understanding the significance of ET-1 in CHF and provide strategies for ET-1 antagonism. Although acute endothelin (ET) receptor antagonism improves systemic hemodynamics in CHF, clinical trials with chronic ET receptor antagonism report worsening CHF symptoms. In a canine model of progressive left ventricular dysfunction, we demonstrated activation of myocardial and plasma ET-1 without activation of the RAS during transition to overt CHF, suggesting that ET-1 contributes to this transition. We next evaluated the effects of chronic oral ET-A receptor antagonism on neurohumoral function, renal hemodynamics, and sodium excretion in pacing-induced CHF. After 7 days of treatment (n=7) with ET-A receptor antagonism (with LU135252), sodium excretion did not improve in treated versus untreated CHF (n=6). Furthermore, both plasma renin activity and plasma ET-1 increased with ET-A receptor blockade. Activation of the myocardial and plasma ET-1 systems precedes activation of the myocardial and plasma RAS in CHF. ET-A receptor antagonism in experimental CHF further activates the RAS without improving sodium excretion. These findings suggest an important role for ET-1 in the progression of CHF and a potential mechanism for the exacerbation of CHF symptoms observed in clinical trials with chronic ET receptor antagonism. Further studies with combined modulation of the ET and other neurohumoral systems in CHF are required.

  12. A method to evaluate the renin-angiotensin system in rat renal cortex using a microdialysis technique combined with HPLC-fluorescence detection.

    Science.gov (United States)

    Kajiro, Toshi; Nakajima, Yuki; Fukushima, Takeshi; Imai, Kazuhiro

    2002-09-01

    A microdialysis (MD) technique, combined with HPLC-fluorescence (FL) detection, was developed for the evaluation of the tissue-specific renin-angiotensin system (RAS) in the rat renal cortex. An MD probe constructed with a hydrophilic hollow fiber dialysis tubing, AN69, showed high recovery (more than 50%) in vitro for all four angiotensins: angiotensin I (Ang I), Ang II, Ang III, and Ang (1-7). Angiotensins, successfully derivatized with m-BS-ABD-F, a water-soluble fluorogenic reagent that has a 2,1,3-benzoxadiazole (benzofurazan) structure, could be simultaneously determined by coupled-column HPLC. The detection limit for Ang I, Ang II, Ang III, and Ang (1-7) were 94, 44, 47, and 83 fmol, respectively. All these peptides were determined with good linearity (0.0125-3.1 microM, equivalent to 0.25-62 pmol, correlation coefficient >0.99) and good precision (recovery >91%). In the MD studies, generation of Ang (1-7) and Ang II was observed when Ang I was perfused, and Ang (1-7) was the major biologically active angiotensin found in the dialysate samples. The concentration of Ang (1-7) and Ang II in the dialysate samples showed good correlation to that of Ang I in a MD perfusate (20-100 microM). Cleavage of Ang I to Ang (1-7) was drastically suppressed by the co-perfusion of phoshoramidon (0.5-5 mM), an inhibitor of neprilysin, which generates Ang (1-7) from Ang I. These results are consistent with the previously reported characteristics of tissue-specific renal RAS, suggesting that our MD/HPLC-FL system may have the potential to be employed to evaluate tissue-specific RAS in the rat renal cortex.

  13. Increased expression of the renin-angiotensin system and mast cell density but not of angiotensin-converting enzyme II in late stages of human heart failure.

    Science.gov (United States)

    Batlle, Montserrat; Roig, Eulàlia; Perez-Villa, Fèlix; Lario, Sergio; Cejudo-Martin, Pilar; García-Pras, Ester; Ortiz, José; Roqué, Mercé; Orús, Josefina; Rigol, Montserrat; Heras, Magdalena; Ramírez, José; Jimenez, Wladimiro

    2006-09-01

    The activation of the renin-angiotensin system (RAS) contributes to the progression of left ventricular dysfunction. A novel human homologue of the angiotensin-converting enzyme (ACE), named ACE2, has been described but its role in human heart failure (HF) has not been elucidated. Besides, there is controversy as to whether the major angiotensin II-forming-activity in heart is ACE or chymase released from mast cells. Furthermore, long-term blockade of nitric oxide (NO) synthesis has been shown to increase ACE activity. To assess the locally activated vasoactive mediators that may contribute to the ventricular deterioration process, we sought to simultaneously analyze their expression in failing hearts. We analyzed left ventricular biopsies from 30 patients with heart failure undergoing heart transplantation and 12 organ donors. The mRNA levels of ACE, ACE2, chymase and endothelial nitric oxide synthase (eNOS), were quantified by real-time polymerase chain reaction and mast cell density was assessed by immunohistochemistry. The mRNA levels of the atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP) were also quantified as controls. There was higher ACE and chymase mRNA expression and mast cell density in failing than in control myocardium and no changes in ACE2 expression were detected. eNOS mRNA levels were lower in failing hearts. Both ANP and BNP expression were higher in pathological than in control samples. These data document a decompensation of vasoactive systems that may contribute to the progressive impairment of the myocardial function in HF. On the other hand, ACE2 mRNA expression is not altered in human end-stage HF.

  14. Dysregulation of microRNAs and renin-angiotensin system in high salt diet-induced cardiac dysfunction in uninephrectomized rats.

    Science.gov (United States)

    Amara, Venkateswara Rao; Surapaneni, Sunil Kumar; Tikoo, Kulbhushan

    2017-01-01

    Uninephrectomy is not associated with major adverse events in cardiovascular and renal functions of live kidney donors. The effect of high salt diet on the quality of life of live kidney donors is largely unknown. Hence in this study, we aimed to determine the effect of high salt diet on the alterations of renin-angiotensin system and microRNAs leading to CV and renal dysfunction in uninephrectomized rats. In order to mimic clinical scenario, uninephrectomized male Sprague Dawley rats were fed initially with normal pellet diet for 12 weeks and then for 20 weeks with high salt (10% w/w NaCl) diet. At the end of the study, biochemical, functional, histological and molecular parameters were measured. High salt diet feeding resulted in renal dysfunction & fibrosis, decreased baroreflex sensitivity, increased in vivo cardiovascular reactivity to angiotensin II owing to upregulation of angiotensin II type 1 receptors and L-type calcium channels leading to cardiovascular dysfunction in uninephrectomized rats (UNX+HSD) worse than that of normal (binephric) rats fed with high salt diet (HSD). Protein expression of functional and hypertrophic protein markers revealed decreased SERCA, p-AMPK and increased p-AKT. Interestingly, levels of miR-25, miR-451 and miR-155 increased and miR-99 decreased in heart of uninephrectomized rats fed with high salt. However, circulating miR-25 and miR-451 levels decreased and miR-99b increased in these animals. Our study points out that since tissue and circulating levels of miRNAs are not similar, caution must be exercised during the usage of miRs as diagnostic or prognostic biomarkers. To our knowledge, we are the first to show that epigenetic alterations result in cardiac dysfunction in uninephrectomized rats fed with high salt diet.

  15. Effects of Renin-Angiotensin System Inhibitors on Renal Expression of Renalase in Sprague-Dawley Rats Fed With High Salt Diet.

    Science.gov (United States)

    Wang, Yang; Xie, Bing-Qing; Gao, Wei-Hua; Yan, Ding-Yi; Zheng, Wen-Ling; Lv, Yong-Bo; Cao, Yu-Meng; Hu, Jia-Wen; Yuan, Zu-Yi; Mu, Jian-Jun

    2015-01-01

    The aim of our study was to investigate the effect of high-salt diet on the renal expression of renalase and the potential role of the local renin-angiotensin system in this process. Sprague-Dawley (SD) rats were divided into groups according to salt content in diet and drug treatment as follows: normal-salt diet (NS), high-salt diet (HS), high-salt intake with hydralazine (HS+H), high-salt diet with enalapril (HS+E), and high-salt diet with valsartan (HS+V). The dietary intervention and drugs were given for four weeks. Renin activity and angiotensin II type 1 receptor (AT1R) levels were detected by real-time PCR. Renalase mRNA and protein were also measured. After four weeks, systolic blood pressure and proteinuria were significantly increased in the HS group with respect to the NS group. Dietary salt intake caused a dramatic decrease in renalase expression in the rat kidneys. Renal cortex renin and AT1R increased significantly in the HS and HS+H groups. Urinary protein was positively correlated with renal renin and AT1R levels. However, in the HS+E and HS+V groups, enalapril and valsartan failed to influence renal renalase expression but abolished the increase in proteinuria, renal cortex renin, and AT1R levels with respect to the HS group. This study indicates that high salt intake reduces renal expression, and renal RAS may be not involved in the regulation of renalase in SD rats fed with high-salt diet. © 2015 The Author(s) Published by S. Karger AG, Basel.

  16. Evaluation of the Clinical Utility of Renin-Angiotensin System Inhibitors in Patients Undergoing Radical Surgery for Urothelial Carcinoma of the Upper Urinary Tract.

    Science.gov (United States)

    Yoshida, Takashi; Matsuzaki, Tomoaki; Murota, Takashi; Kawa, Gen; Matsuda, Tadashi; Kinoshita, Hidefumi

    2017-12-01

    Renin-angiotensin system (RAS) inhibitors are effective for treating patients with cancer. The present study evaluated the impact of RAS inhibitors, including angiotensin-2 converting enzyme inhibitors and angiotensin 2 receptor blockers, after patients underwent radical surgery for upper urinary tract urothelial carcinoma (UTUC). This retrospective study included 312 patients with nonmetastatic UTUC who underwent radical surgery. The oncological outcomes of patients treated or not treated with RAS inhibitors following surgery were evaluated. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were assessed using the Kaplan-Meier method and Cox regression analysis. The median follow-up duration after radical surgery was 44.7 months. The 5-year RFS, CSS, and OS rates of patients who did or did not receive RAS inhibitors were 82.3% versus 68.9% (P = .018), 88.9% versus 71.8% (P = .0044), and 68.7% versus 61.8% (P = .047), respectively. Multivariable analyses revealed that the use of RAS inhibitors was an independent prognostic factor for RFS, CSS, and OS (hazard ratio [HR] 0.48, P = .013; HR 0.31, P = .002; and HR 0.52, P = .01, respectively). Moreover, patients treated with RAS inhibitors versus untreated patients had better 5-year RFS compared with those in the pT2 and < pN1 subgroups (pT2: 100.0% vs. 62.2%, P = .014 and < pN1: 87.2% vs. 74.7%, P = .034). RAS inhibitors significantly improved RFS, CSS, and OS of patients with UTUC who underwent radical surgery. These agents may be particularly beneficial for patients with stage pT2 or < pN1 disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial.

    Science.gov (United States)

    de Vries, Laura V; Dobrowolski, Linn C; van den Bosch, Jacqueline J O N; Riphagen, Ineke J; Krediet, C T Paul; Bemelman, Frederike J; Bakker, Stephan J L; Navis, Gerjan

    2016-06-01

    In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore studied the effects of dietary sodium restriction on BP and urinary albumin excretion (UAE) in kidney transplant recipients receiving RAAS blockade. Two-center randomized crossover trial. Stable outpatient kidney transplant recipients with creatinine clearance > 30mL/min, BP ≥120/80mmHg, receiving stable RAAS blockade therapy. 6-week regular-sodium diet (target, 150mmol/24 h) and a 6-week low-sodium diet (target, 50mmol/24 h). Main outcome parameters were systolic and diastolic BP, UAE, and estimated glomerular filtration rate (eGFR) at the end of each diet period. Dietary adherence was assessed by 24-hour urinary sodium excretion. We randomly assigned 23 kidney transplant recipients, of whom 22 (mean age, 58±8 [SD] years; 50% men; mean eGFR, 51±21mL/min/1.73m(2)) completed the study. One patient withdrew from the study because of concerns regarding orthostatic hypotension on the low-sodium diet. Sodium excretion decreased from 164±50mmol/24 h during the regular-sodium diet to 87±55mmol/24 h during the low-sodium diet (mean difference, -77 [95% CI, -110 to -44] mmol/24 h; Padherence to sodium diet was achieved in 86% of patients. In stable kidney transplant recipients receiving RAAS blockade, dietary sodium restriction effectively reduces BP without affecting eGFR. Dietary sodium restriction is relevant to BP management in kidney transplant recipients receiving RAAS blockade. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  18. Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression.

    Science.gov (United States)

    Gonzalez-Calero, Laura; Martin-Lorenzo, Marta; de la Cuesta, Fernando; Maroto, Aroa S; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Pulido-Olmo, Helena; Segura, Julian; Barderas, Maria G; Ruilope, Luis M; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2016-01-16

    Hypertension is a multi-factorial disease of increasing prevalence and a major risk factor for cardiovascular mortality even in the presence of adequate treatment. Progression of cardiovascular disease (CVD) occurs frequently during chronic renin-angiotensin-system (RAS) suppression, and albuminuria is a marker of CV risk. High prevalence of albuminuria in treated hypertensive patients has been demonstrated, but there are no available markers able to predict evolution. The aim of this study was the identification of novel indicators of albuminuria progression measurable in urine of diabetic and non-diabetic patients. 1143 hypertensive patients under chronic treatment were followed for a minimum period of 3 years. Among them, 105 diabetic and non-diabetic patients were selected and classified in three groups according to albuminuria development during follow-up: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Differential urine analysis was performed by 2D gel electrophoresis (2D-DIGE) and further confirmed by liquid chromatography-mass spectrometry. Non-parametric statistical tests were applied. CD59 glycoprotein and alpha-1 antitrypsin (AAT) resulted already altered in patients developing albuminuria de novo, with a similar response in those with maintained albuminuria. A prospective study in a sub-group of normoalbuminuric patients who were clinically followed up for at least 1 year from urine sampling, revealed CD59 and AAT proteins significantly varied in the urine collected from normoalbuminurics who will negatively progress, serving as predictors of future albuminuria development. CD59 and AAT proteins are significantly altered in hypertensive patients developing albuminuria. Interestingly, CD59 and AAT are able to predict, in normoalbuminuric individuals, who will develop albuminuria in the future, being potential predictors of vascular damage and CV risk. These findings

  19. Beta2-adrenergic receptor genotype affects the renin-angiotensin-aldosterone system response to the Dietary Approaches to Stop Hypertension (DASH) dietary pattern.

    Science.gov (United States)

    Sun, Bei; Williams, Jonathan S; Svetkey, Laura P; Kolatkar, Nikheel S; Conlin, Paul R

    2010-08-01

    Beta(2)-adrenergic receptor (beta2-AR) is a susceptibility locus for hypertension, and polymorphisms at this site relate to salt sensitivity and low plasma renin activity (PRA). The Dietary Approaches to Stop Hypertension (DASH) dietary pattern lowers blood pressure and appears to interact with the renin-angiotensin-aldosterone system (RAAS). We hypothesized that the DASH diet associates with increased RAAS activity, and genotype status at beta2-AR G46A modifies this response. We genotyped participants in the DASH-Sodium study (n = 372) at beta2-AR G46A to determine the association with blood pressure, RAAS components, and consumption of the DASH diet. We used 2-way mixed linear regression and an additive model for all primary analyses. Mean (+/-SEM) PRA was significantly higher in participants in the DASH group than in participants in the control group (0.68 +/- 0.03 compared with 0.54 +/- 0.03 ng x mL(-1) x h(-1), P = 0.002). Serum aldosterone, urinary aldosterone, and urinary potassium concentrations were also significantly higher in the DASH group (P diet interactions for changes in systolic blood pressure (SBP) and concentrations of aldosterone and urinary potassium (P for interaction = 0.048, 0.017, and 0.001 for SBP and aldosterone and urinary potassium concentrations, respectively). There was an association between the A allele of beta2-AR G46A and greater blood pressure reduction and blunted aldosterone and PRA responses to the DASH diet. Our results indicate that the DASH diet lowers blood pressure and increases PRA and aldosterone concentrations. There is an association between the G46A polymorphism of beta2-AR and blood pressure and RAAS responses to the DASH diet, which suggests that beta2-AR may be a genetic modifier of DASH-diet responsiveness. This trial was registered at clinicaltrials.gov as NCT00000608.

  20. Effect of exercise training on the renin-angiotensin-aldosterone system in healthy individuals: a systematic review and meta-analysis.

    Science.gov (United States)

    Goessler, Karla; Polito, Marcos; Cornelissen, Véronique Ann

    2016-03-01

    The aim of this systematic review and meta-analysis was to evaluate the effect of exercise training on parameters of the renin-angiotensin-aldosterone system (RAAS) in healthy adults, and to investigate the relation with training induced changes in blood pressure. A systematic search was conducted and we included randomized controlled trials lasting ⩾4 weeks investigating the effects of exercise on parameters of the RAAS in healthy adults (age ⩾18 years) and published in a peer-reviewed journal up to December 2013. Fixed effects models were used and data are reported as weighted means and 95% confidence limits (CL). Eleven randomized controlled trials with a total of 375 individuals were included. Plasma renin activity was reduced after exercise training (n= 7 trials, standardized mean difference -0.25 (95% CL -0.5 to -0.001), P=0.049), whereas no effect was observed on serum aldosterone ((n= 3 trials; standardized mean difference -0.79 (-1.97 to +0.39)) or angiotensin II (n=3 trials; standardized mean difference -0.16 (-0.61 to +0.30). Significant reductions in systolic blood pressure -5.65 mm Hg (-8.12 to -3.17) and diastolic blood pressure -3.64 mm Hg (-5.4 to -1.91) following exercise training were observed. No relation was found between net changes in plasma renin activity and net changes in blood pressure (P>0.05). To conclude, although we observed a significant reduction in plasma renin activity following exercise training this was not related to the observed blood pressure reduction. Given the small number of studies and small sample sizes, larger well-controlled randomized studies are required to confirm our results and to investigate the potential role of the RAAS in the observed improvements in blood pressure following exercise training.

  1. Individual variability in response to renin angiotensin aldosterone system inhibition predicts cardiovascular outcome in patients with type 2 diabetes: A primary care cohort study.

    Science.gov (United States)

    Apperloo, Ellen M; Pena, Michelle J; de Zeeuw, Dick; Denig, Petra; Heerspink, Hiddo J L

    2018-01-18

    To assess variability in systolic blood pressure (SBP) and albuminuria (urinary albumin creatinine ratio [UACR]) responses in patients with type 2 diabetes mellitus initiating renin angiotensin aldosterone system (RAAS) inhibition, and to assess the association of response variability with cardiovascular outcomes. We performed an observational cohort study in patients with type 2 diabetes who started RAAS inhibition between 2007 and 2013 (n = 1600). Patients were identified from general practices in the Netherlands. Individual response in SBP and UACR was assessed during 15 months' follow-up. Patients were categorized as: good responders (∆SBP 0% or ∆SBP >0 mm Hg and ∆UACR 0 mm Hg and ∆UACR >0%). Multivariable Cox regression was performed to test the association between initial RAAS inhibition response and subsequent cardiovascular outcomes. After starting RAAS inhibition, the mean SBP change was -13.2 mm Hg and the median UACR was -36.6%, with large between-individual variability, both in SBP [5th to 95th percentile: 48.5-20] and UACR [5th to 95th percentile: -87.6 to 171.4]. In all, 812 patients (51%) were good responders, 353 (22%) had a good SBP but poor UACR response, 268 (17%) had a good UACR but poor SBP response, and 167 patients (10%) were poor responders. Good responders had a lower risk of cardiovascular events than poor responders (hazard ratio 0.51, 95% confidence interval 0.30-0.86; P = .012). SBP and UACR response after RAAS inhibition initiation varied between and within individual patients with type 2 diabetes treated in primary care. Poor responders had the highest risk of cardiovascular events, therefore, more efforts are needed to develop personalized treatment plans for these patients. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  2. Clinical impacts of inhibition of renin-angiotensin system in patients with acute ST-segment elevation myocardial infarction who underwent successful late percutaneous coronary intervention.

    Science.gov (United States)

    Park, Hyukjin; Kim, Hyun Kuk; Jeong, Myung Ho; Cho, Jae Yeong; Lee, Ki Hong; Sim, Doo Sun; Yoon, Nam Sik; Yoon, Hyun Ju; Hong, Young Joon; Kim, Kye Hun; Park, Hyung Wook; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Kim, Young Jo; Cho, Myeong Chan; Kim, Chong Jim

    2017-01-01

    Successful percutaneous coronary intervention (PCI) of the occluded infarct-related artery (IRA) in latecomers may improve long-term survival mainly by reducing left ventricular remodeling. It is not clear whether inhibition of renin-angiotensin system (RAS) brings additional better clinical outcomes in this specific population subset. Between January 2008 and June 2013, 669 latecomer patients with acute ST-segment elevation myocardial infarction (STEMI) (66.2±12.1 years, 71.0% males) in Korea Acute Myocardial Infarction Registry (KAMIR) who underwent a successful PCI were enrolled. The study population underwent a successful PCI for a totally occluded IRA. They were divided into two groups according to whether they were prescribed RAS inhibitors at the time of discharge: group I (RAS inhibition, n=556), and group II (no RAS inhibition, n=113). During the one-year follow-up, major adverse cardiac events (MACE), which consist of cardiac death and myocardial infarction, occurred in 71 patients (10.6%). There were significantly reduced incidences of MACE in the group I (hazard ratio=0.34, 95% confidence interval 0.199-0.588, p=0.001). In subgroup analyses, RAS inhibition was beneficial in patients with male gender, history of hypertension or diabetes mellitus, and even in patients with left ventricular ejection fraction (LVEF) ≥40%. In the baseline and follow-up echocardiographic data, benefit in changes of LVEF and left ventricular end-systolic volume was noted in group I. In latecomers with STEMI, RAS inhibition improved long-term clinical outcomes after a successful PCI, even in patients with low risk who had relatively preserved LVEF. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  3. Effects of peripherally and centrally applied ghrelin on the oxidative stress induced by renin angiotensin system in a rat model of renovascular hypertension.

    Science.gov (United States)

    Boshra, Vivian; Abbas, Amr M

    2017-07-26

    Renovascular hypertension (RVH) is a result of renal artery stenosis, which is commonly due to astherosclerosis. In this study, we aimed to clarify the central and peripheral effects of ghrelin on the renin-angiotensin system (RAS) in a rat model of RVH. RVH was induced in rats by partial subdiaphragmatic aortic constriction. Experiment A was designed to assess the central effect of ghrelin via the intracerebroventricular (ICV) injection of ghrelin (5 μg/kg) or losartan (0.01 mg/kg) in RVH rats. Experiment B was designed to assess the peripheral effect of ghrelin via the subcutaneous (SC) injection of ghrelin (150 μg/kg) or losartan (10 mg/kg) for 7 consecutive days. Mean arterial blood pressure (MAP), heart rate, plasma renin activity (PRA), and oxidative stress markers were measured in all rats. In addition, angiotensin II receptor type 1 (AT1R) concentration was measured in the hypothalamus of rats in Experiment B. RVH significantly increased brain AT1R, PRA, as well as the brain and plasma oxidative stress. Either SC or ICV ghrelin or losartan caused a significant decrease in MAP with no change in the heart rate. Central ghrelin or losartan caused a significant decrease in brain AT1R with significant alleviation of the brain oxidative stress. Central ghrelin caused a significant decrease in PRA, whereas central losartan caused a significant increase in PRA. SC ghrelin significantly decreased PRA and plasma oxidative stress, whereas SC losartan significantly increased PRA and decreased plasma oxidative stress. The hypotensive effect of ghrelin is mediated through the amelioration of oxidative stress, which is induced by RAS centrally and peripherally.

  4. Endoplasmic reticulum stress increases brain MAPK signaling, inflammation and renin-angiotensin system activity and sympathetic nerve activity in heart failure.

    Science.gov (United States)

    Wei, Shun-Guang; Yu, Yang; Weiss, Robert M; Felder, Robert B

    2016-10-01

    We previously reported that endoplasmic reticulum (ER) stress is induced in the subfornical organ (SFO) and the hypothalamic paraventricular nucleus (PVN) of heart failure (HF) rats and is reduced by inhibition of mitogen-activated protein kinase (MAPK) signaling. The present study further examined the relationship between brain MAPK signaling, ER stress, and sympathetic excitation in HF. Sham-operated (Sham) and HF rats received a 4-wk intracerebroventricular (ICV) infusion of vehicle (Veh) or the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 10 μg/day). Lower mRNA levels of the ER stress biomarkers GRP78, ATF6, ATF4, and XBP-1s in the SFO and PVN of TUDCA-treated HF rats validated the efficacy of the TUDCA dose. The elevated levels of phosphorylated p44/42 and p38 MAPK in SFO and PVN of Veh-treated HF rats, compared with Sham rats, were significantly reduced in TUDCA-treated HF rats as shown by Western blot and immunofluorescent staining. Plasma norepinephrine levels were higher in Veh-treated HF rats, compared with Veh-treated Sham rats, and were significantly lower in the TUDCA-treated HF rats. TUDCA-treated HF rats also had lower mRNA levels for angiotensin converting enzyme, angiotensin II type 1 receptor, tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and NF-κB p65, and a higher mRNA level of IκB-α, in the SFO and PVN than Veh-treated HF rats. These data suggest that ER stress contributes to the augmented sympathetic activity in HF by inducing MAPK signaling, thereby promoting inflammation and renin-angiotensin system activity in key cardiovascular regulatory regions of the brain.

  5. Leptin Mediate High Fat Diet Sensitization of Angiotensin II-elicited Hypertension by Upregulating the Brain Renin-Angiotensin System and Inflammation

    Science.gov (United States)

    Xue, Baojian; Yu, Yang; Zhang, Zhongming; Guo, Fang; Beltz, Terry G.; Thunhorst, Robert L.; Felder, Robert B.; Johnson, Alan Kim

    2016-01-01

    Obesity is characterized by increased circulating levels of the adipocyte-derived hormone leptin, which can increase sympathetic nerve activity and raise blood pressure. A previous study revealed that rats fed a high fat diet (HFD) have an enhanced hypertensive response to subsequent angiotensin (Ang) II administration that is mediated at least in part by increased activity of brain renin-angiotensin system (RAS) and proinflammatory cytokines (PICs). The present study tested whether leptin mediates this HFD-induced sensitization of Ang II-elicited hypertension by interacting with brain RAS and PICs mechanisms. Rats fed a HFD for 3 weeks had significant increases in white adipose tissue mass, plasma leptin levels and mRNA expression of leptin and its receptors in the lamina terminalis (LT) and hypothalamic paraventricular nucleus (PVN). Central infusion of a leptin receptor antagonist during HFD feeding abolished HFD sensitization of Ang II-elicited hypertension. Furthermore, central infusion of leptin mimicked the sensitizing action of HFD. Concomitant central infusions of the AT1-R antagonist irbesartan, the TNF-α synthesis inhibitor pentoxifylline, or the inhibitor of microglial activation minocycline prevented the sensitization produced by central infusion of leptin. RT-PCR analysis indicated that either HFD or leptin administration upregulated mRNA expression of several components of the RAS and PICs in the LT and PVN. The leptin antagonist and the inhibitors of AT1-R, TNF-α synthesis and microglial activation all reversed the expression of these genes. The results suggest that HFD-induced sensitization of Ang II-elicited hypertension is mediated by leptin through upregulation of central RAS and PICs. PMID:27021010

  6. An interaction of renin-angiotensin and kallikrein-kinin systems contributes to vascular hypertrophy in angiotensin II-induced hypertension: in vivo and in vitro studies.

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    Graziela S Ceravolo

    Full Text Available The kallikrein-kinin and renin-angiotensin systems interact at multiple levels. In the present study, we tested the hypothesis that the B1 kinin receptor (B1R contributes to vascular hypertrophy in angiotensin II (ANG II-induced hypertension, through a mechanism involving reactive oxygen species (ROS generation and extracellular signal-regulated kinase (ERK1/2 activation. Male Wistar rats were infused with vehicle (control rats, 400 ng/Kg/min ANG II (ANG II rats or 400 ng/Kg/min ANG II plus B1 receptor antagonist, 350 ng/Kg/min des-Arg(9-Leu(8-bradykinin (ANGII+DAL rats, via osmotic mini-pumps (14 days or received ANG II plus losartan (10 mg/Kg, 14 days, gavage - ANG II+LOS rats. After 14 days, ANG II rats exhibited increased systolic arterial pressure [(mmHg 184 ± 5.9 vs 115 ± 2.3], aortic hypertrophy; increased ROS generation [2-hydroxyethidium/dihydroethidium (EOH/DHE: 21.8 ± 2.7 vs 6.0 ± 1.8] and ERK1/2 phosphorylation (% of control: 218.3 ± 29.4 vs 100 ± 0.25]. B1R expression was increased in aortas from ANG II and ANG II+DAL rats than in aortas from the ANG II+LOS and control groups. B1R antagonism reduced aorta hypertrophy, prevented ROS generation (EOH/DHE: 9.17 ± 3.1 and ERK1/2 phosphorylation (137 ± 20.7% in ANG II rats. Cultured aortic vascular smooth muscle cells (VSMC stimulated with low concentrations (0.1 nM of ANG II plus B1R agonist exhibited increased ROS generation, ERK1/2 phosphorylation, proliferating-cell nuclear antigen expression and [H3]leucine incorporation. At this concentration, neither ANG II nor the B1R agonist produced any effects when tested individually. The ANG II/B1R agonist synergism was inhibited by losartan (AT1 blocker, 10 µM, B1R antagonist (10 µM and Tiron (superoxide anion scavenger, 10 mM. These data suggest that B1R activation contributes to ANG II-induced aortic hypertrophy. This is associated with activation of redox-regulated ERK1/2 pathway that controls aortic smooth muscle cells growth

  7. Renin-angiotensin-aldosterone system blockers for heart failure with reduced ejection fraction or left ventricular dysfunction: Network meta-analysis.

    Science.gov (United States)

    Xie, Wuxiang; Zheng, Fanfan; Song, Xiaoyu; Zhong, Baoliang; Yan, Li

    2016-02-15

    Renin-angiotensin-aldosterone system (RAAS) blockers are effective therapies for heart failure and reduced ejection fraction (HFrEF) or left ventricular dysfunction (LVD). We aimed to assess the efficacy and safety of RAAS blockers in these patients. We searched MEDLINE, EMBASE, and Cochrane Library in May 2015. Twenty-one double-blind randomized controlled trials (RCTs) with 69,229 patients were included this network meta-analysis. Compared with placebo, an angiotensin receptor-neprilysin inhibitor (ARNI) had the highest probability of reducing all-cause mortality (odds ratio [OR]=0.67, 95% credible interval [CrI]: 0.48-0.86), followed by an aldosterone receptor antagonist (ARA, OR=0.74, 95% CrI: 0.62-0.88) and an angiotensin-converting enzyme inhibitor (ACEI, OR=0.80, 95% CrI: 0.71-0.89). The most efficacious therapy for preventing heart failure hospitalization was ARNI (OR=0.55, 95% CrI: 0.40-0.71), followed by combination therapy with an angiotensin II receptor blocker (ARB) plus an ACEI (OR=0.61, 95% CrI: 0.49-0.75), then an ACEI alone (OR=0.69, 95% CrI: 0.61-0.77). Sensitivity analysis restricted to nine RCTs with a high background use of ACEI and/or ARB (>80%) indicated that adding an ARA to current standard therapy significantly reduced mortality (OR=0.73, 95% CrI: 0.51-0.95) and hospitalization risk (OR=0.67, 95% CrI: 0.47-0.87), but did not significantly increase the discontinuation risk (OR=1.29, 95% CrI: 0.83-2.31). ARNI has the highest probability of being the most efficacious therapy for HFrEF in reducing death and hospitalization for heart failure. ARA has the most favorable benefit-risk profile as an adjunct to background ACEI and/or ARB therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Antiproteinuric effect of add-on paricalcitol in CKD patients under maximal tolerated inhibition of renin-angiotensin system: a prospective observational study

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    De Nicola Luca

    2012-11-01

    Full Text Available Abstract Background Whether paricalcitol (PCT reduces proteinuria in the presence of intensified inhibition of Renin-Angiotensin-System (RAS is poorly studied. We evaluated the antiproteinuric effect of PCT in non-dialysis chronic kidney disease (CKD patients with proteinuria greater than 0.5 g/24 h persisting despite anti-RAS therapy titrated to minimize proteinuria in the absence of adverse effects. Methods Forty-eight CKD patients were studied in the first six months of add-on oral PCT (1 mcg/day and three months after drug withdrawal. Results Males were 87.5%, age 63 ± 14 yrs, systolic/diastolic blood pressure (BP 143 ± 22/78 ± 11 mmHg, eGFR 29.7 ± 14.5 mL/min/1.73 m2, diabetes 40%, and cardiovascular disease 38%. At referral in the center (28 months prior to study baseline, proteinuria was 2.44 (95% CI 1.80-3.04 g/24 h with 6 patients not receiving any anti-RAS and 42 treated with a single agent, at low dosage in most cases. At study baseline, twenty patients were under 2–3 anti-RAS drugs while twenty-eight received 1 agent at full dose and proteinuria resulted to be reduced versus referral to 1.23 g/24 h (95%CI 1.00-1.51. Six months of add-on PCT significantly decreased proteinuria to 0.61 g/24 h (95%CI 0.40-0.93, with levels less than 0.5 g/24 h achieved in 37.5% patients, in the absence of changes of BP and GFR. Proteinuria recovered to basal value after drug withdrawal. The extent of antiproteinuric response to PCT was positively associated with diabetes, eGFR and daily Na excretion (R2 = 0.459, P  Conclusions In CKD patients, add-on PCT induces a significant reduction of proteinuria that is evident despite intensified anti-RAS therapy and larger in the presence of diabetes, higher GFR and unrestricted salt intake.

  9. Antiproteinuric effect of add-on paricalcitol in CKD patients under maximal tolerated inhibition of renin-angiotensin system: a prospective observational study.

    Science.gov (United States)

    De Nicola, Luca; Conte, Giuseppe; Russo, Domenico; Gorini, Antonio; Minutolo, Roberto

    2012-11-20

    Whether paricalcitol (PCT) reduces proteinuria in the presence of intensified inhibition of Renin-Angiotensin-System (RAS) is poorly studied. We evaluated the antiproteinuric effect of PCT in non-dialysis chronic kidney disease (CKD) patients with proteinuria greater than 0.5 g/24 h persisting despite anti-RAS therapy titrated to minimize proteinuria in the absence of adverse effects. Forty-eight CKD patients were studied in the first six months of add-on oral PCT (1 mcg/day) and three months after drug withdrawal. Males were 87.5%, age 63 ± 14 yrs, systolic/diastolic blood pressure (BP) 143 ± 22/78 ± 11 mmHg, eGFR 29.7 ± 14.5 mL/min/1.73 m(2), diabetes 40%, and cardiovascular disease 38%. At referral in the center (28 months prior to study baseline), proteinuria was 2.44 (95% CI 1.80-3.04) g/24 h with 6 patients not receiving any anti-RAS and 42 treated with a single agent, at low dosage in most cases. At study baseline, twenty patients were under 2-3 anti-RAS drugs while twenty-eight received 1 agent at full dose and proteinuria resulted to be reduced versus referral to 1.23 g/24 h (95%CI 1.00-1.51). Six months of add-on PCT significantly decreased proteinuria to 0.61 g/24 h (95%CI 0.40-0.93), with levels less than 0.5 g/24 h achieved in 37.5% patients, in the absence of changes of BP and GFR. Proteinuria recovered to basal value after drug withdrawal. The extent of antiproteinuric response to PCT was positively associated with diabetes, eGFR and daily Na excretion (R(2) = 0.459, P proteinuria that is evident despite intensified anti-RAS therapy and larger in the presence of diabetes, higher GFR and unrestricted salt intake.

  10. In Vitro Regulation of Enzymes of the Renin-angiotensin-aldosterone System by Isoquercitrin, Phloridzin and their Long Chain Fatty Acid Derivatives

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    Khushwant S. Bhullar

    2014-05-01

    Full Text Available Background: Hypertension is a crucial risk factor for development of cardiovascular and neurological diseases. Flavonoids exhibit a wide range of biological effects and have had increased interest as a dietary approach for the prevention or possible treatment of hypertension. However, continuous efforts have been made to structurally modify natural flavonoids with the hope of improving their biological activities. One of the methods used for the possible enhancement of flavonoid efficacy is enzymatic esterification of flavonoids with fatty acids. Objective: The current study is designed to investigate the antihypertensive activity of isoquercitrin (quercetin-3-O-glucoside, Q3G and phloridzin (PZ in comparison to their twelve long chain fatty acid derivatives via enzymatic inhibition of renin angiotensin aldosterone system (RAAS enzymes. Methods: The novel flavonoid esters were synthesized by the acylation of isoquercitrin and phloridzin with long chain unsaturated and saturated fatty acids (C18–C22. These acylated products were then tested for their in vitro angiotensin converting enzyme (ACE, renin and aldosterone synthase activities. Results: The linoleic and α-linolenic acid esters of PZ were the strongest (IC50 69.9-70.9 µM while Q3G and PZ (IC50 >200 µM were the weakest renin inhibitors in vitro (p≤0.05. The eicosapentaenoic acid ester of PZ (IC50 16.0 µM was the strongest inhibitor of ACE, while PZ (IC50 124.0 µM was the weakest inhibitor (p≤0.05 among all tested compounds. However, all investigated compounds had low (5.0-11.9% or no effect on aldosterone synthase inhibition (p≤0.05. The parent compound Q3G and the eicosapentaenoic acid ester of PZ emerged as the strongest ACE inhibitors. Conclusions: The structural modification of Q3G and PZ significantly improved their antihypertensive activities. The potential use of PZ derivatives as natural health products to treat hypertension needs to be further evaluated

  11. The impact of age and sex on the reporting of cough and angioedema with renin-angiotensin system inhibitors: a case/noncase study in VigiBase.

    Science.gov (United States)

    Alharbi, Fawaz F; Kholod, Anzhelika A V; Souverein, Patrick C; Meyboom, Ronald H; de Groot, Mark C H; de Boer, Anthonius; Klungel, Olaf H

    2017-12-01

    The purpose of this study was to assess the impact of age and sex on the reporting of cough and angioedema related to renin-angiotensin system (RAS) inhibitors. A case/noncase study was performed in VigiBase. Two case groups were identified, reports of cough and reports of angioedema, and noncases were all reports of all other adverse events. Logistic regression analysis was used to assess the association between reporting of cough and angioedema with each class of RAS inhibitors stratified by age/sex and to control for confounding. The reporting of cough with angiotensin-converting enzyme (ACE) inhibitors was significantly higher in women than in men [adjusted reporting odds ratio (ROR): 44.0, 95% CI (43.2-44.8) for women vs. 29.2, 95% CI (28.5-29.9) for men]. There was no difference in reporting of cough linked to angiotensin receptor blockers (ARBs) and aliskiren between men and women. In contrast, the reporting of angioedema with ACE inhibitors and ARBs was significantly higher in men than in women, but for aliskiren, women had a significantly higher ROR than men [adjusted ROR: 5.20, 95% CI (4.18-6.46) for women vs. 3.04, 95% CI (2.30-4.02) for men]. The reporting of cough with ACE inhibitors was increased with age until reaching a plateau at middle adulthood (40-59 years) and the reporting of angioedema with ACE inhibitors was increased with age until elderly (60-79 years). Age had only a slight effect on the reporting of cough and angioedema with ARBs and aliskiren. Both age and sex have substantial effects on the reporting of cough and angioedema with RAS inhibitors and in particular ACE inhibitors. Further study is needed to determine whether these differences mainly express different adverse drug reaction risks in subgroups or also can be explained by factors influencing reporting. © 2017 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.

  12. 8C.03: A KEY ROLE FOR ENDOTHELIN-1 IN THE PATHOGENESIS OF PREECLAMPSIA AND THE ASSOCIATED SUPPRESSION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM.

    Science.gov (United States)

    Verdonk, K; Saleh, L; Smilde, J E; van Ingen, M M; Garrelds, I M; Friesema, E C; Russcher, H; Steegers, E A P; van den Meiracker, A H; Visser, W; Danser, A H J

    2015-06-01

    Women with preeclampsia (PE) display low renin-angiotensin-aldosterone system (RAAS) activity and a high anti-angiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase-1(sFlt-1) and reduced levels of placental growth factor (PlGF). In the present study, we hypothesized that the RAAS suppression in PE is the consequence of the disturbed angiogenic balance. In a group of pregnant women with hypertensive disease of pregnancy and a group of healthy pregnant women, matched for gestational age (GA) we measured mean arterial blood pressure (MAP), urinary protein-to-creatinine ratio (PCR), and the plasma levels of sFlt-1, PlGF, albumin, creatinine, endothelin-1 (ET-1), renin (concentration and activity, PRC and PRA), angiotensinogen, and aldosterone. Since initial analysis revealed that these parameters strongly correlated with each other, multiple regression analysis was applied to establish independent determinants of ET-1, PRC, aldosterone and PCR. A sFlt-1/PlGF ratio >85 was considered to be representative for a high anti-angiogenic state. Of the 103 pregnant women included, 65 had a sFlt-1/PlGF ratio 85. Plasma ET-1 and creatinine levels were increased in women with a high ratio, whereas PRA and the plasma levels of renin, angiotensinogen, aldosterone and albumin were decreased in these women. The PRA-aldosterone relationship was identical in both groups. Multiple regression analysis revealed that PRC correlated independently with MAP and plasma ET-1 (R2 0.30). In turn, plasma ET-1 correlated positively with sFlt-1 and negatively with PRC (R2 0.52). Independent determinants of plasma aldosterone were GA and PRA (R2 0.56). Finally we found that plasma PlGF, plasma ET-1 and MAP determined PCR (R2 0.69). The high anti-angiogenic state in PE induces ET-1 activation. Together with the increased MAP in PE this factor suppresses renin release, and in parallel (via PRA reduction) aldosterone synthesis. The identical reduction in PRA and

  13. ASSOCIATION OF GENE POLYMORPHISMS OF THE RENIN-ANGIOTENSIN SYSTEM AND ENDOTHELIAL DYSFUNCTION WITH DEVELOPMENT AND SEVERITY OF PORTAL HYPERTENSION IN PATIENTS WITH CHRONIC HEPATITIS C

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    O. V. Taratina

    2016-01-01

    Full Text Available Background: At present, much attention is paid to genetic factors explaining the clinical course of chronic hepatitis C. Aim: To evaluate an association of the gene polymorphisms involved in the formation of endothelial dysfunction (NOS3 894G/T, CYBA 242C/T, MTHFR 677C/T and encoding components of the renin-angiotensin system (ATR1 1166A/C, AGT (-6G/T and 235M/T with development and severity of portal hypertension syndrome in patients with chronic hepatitis C. Materials and methods: 162 patients with chronic hepatitis C and HCV-related cirrhosis (114 women and 48 men were divided into the following groups: no portal hypertension (n = 98, "compensated" (n = 19 and "decompensated" (n = 45 portal hypertension. The gene polymorphisms were assessed by molecular genetic methods. Results: TT genotype of CYBA was more common in patients with portal hypertension than in those without (odds ratio (OR for TT = 3.59, p = 0.031. This difference becomes larger when comparing the decompensated portal hypertension group with the no portal hypertension group (OR TT = 5.46, p = 0.009. Other gene polymorphisms were not associated with development or decompensation of portal hypertension. Multivariate analysis of the impact of genetic, clinical and demographic factors showed that portal hypertension was associated primarily with patients age at the time of the study (Wald's х2 = 14.99 and with their body mass index (Wald's х2 = 4.35. After exclusion of these population-wide risk factors from the model, the development of portal hypertension correlated with the carriage of 235TT genotype of CYBA (Wald's х2 = 6.07, OR = 4.29 and (-6AA genotype AGT (Wald's х2 = 4.73, OR = 4.13, as well as with the lack of protective 235TT genotype AGT (Wald's х2 = 4.06, OR = 0.33. The combined effects of the studied gene polymorphisms on decompensation of the portal hypertension in patients with chronic HCV infection were similar. Conclusion: The development and increase in

  14. Reducing Disease Activity in Animal Models of MS by Activation of the Protective Arm of the Renin-Angiotensin System

    Science.gov (United States)

    2015-10-01

    in EAE is to skew expression of the RAS system in the brain to the anti- inflammatory, regulatory arm. In our proposal we hypothesized that if we were...followed by progressive accruing disability and paralysis with stabilization at a high level of disability. MOG-EAE is similar in many aspects to...progressive MS with extensive neuronal damage both in the brain and spinal cord, and once established treatment intervention can be very limited. Spinal

  15. Radioimmunoassay of renin-angiotensin-aldosterone in patients with adrenal tumors

    International Nuclear Information System (INIS)

    Slavnov, V.N.; Yakovlev, A.A.; Yugrinov, O.G.; Gandzha, T.I.

    1983-01-01

    The results are presented of a study of the renin-angiotensin-aldosterone system in 89 patients with aldosteronoma, corticosteroma, pheochromocytoma and hypertension. Radioimmunoassay was used to measure aldosterone concentration and renin activity in the peripheral blood and blood from vena cava inferior, the renal and adrenal veins, the circadian cycle of their content and the responsiveness of the glomerular zone of the adrenal cortex and the juxtaglomerular renal system under the influence of lasix intake and the change over from a horizontal into vertical position. Patients with adrenal tumors have shown disorders of renin-angiotensin-aldosterone function. Radioimmunoassay of the renin-angiotensin-aldosterone system promotes early detection of adrenal tumors in the general population of patients with hypertension and can be used for control over therapeutic efficacy

  16. The effect of vitamin D on renin-angiotensin system activation and blood pressure: a randomized control trial.

    Science.gov (United States)

    McMullan, Ciaran J; Borgi, Lea; Curhan, Gary C; Fisher, Naomi; Forman, John P

    2017-04-01

    Disruption of vitamin D signaling in rodents causes activation of the rennin-angiotensin system (RAS) and development of hypertension. Observational studies in humans found lower circulating 25-hydroxyvitamin D [25(OH)D] is associated with increased RAS activity and blood pressure (BP). We performed the first randomized control trial to investigate the effects of vitamin D supplementation on the RAS in humans. Vitamin D deficient, [25(OH)D ≤20 ng/ml), overweight individuals without hypertension were randomized into a double-blind, placebo-controlled trial of 8-weeks treatment with ergocalciferol or placebo. Kidney-specific RAS activity, measured using renal plasma flow response to captopril in high sodium balance, was assessed at baseline and 8 weeks, as was systemic RAS activity and 24-h ambulatory BP. In total, 84 participants completed the study. Mean 25[OH]D levels increased from 14.7 to 30.3 ng/ml in the ergocalciferol group, P value vitamin D deficiency on RAS activity or BP after 8 weeks. These findings are not consistent with the hypothesis that vitamin D is a modifiable target for lowering BP in vitamin D deficient individuals.

  17. Family history and renin-angiotensin system gene polymorphisms in Chinese patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Pan, Yan-Hong; Huang, Yan-Mei; Qiao, Yong-Chao; Ling, Wei; Geng, Li-Jun; Xiao, Jian-Long; Zhang, Xiao-Xi; Zhao, Hai-Lu

    2017-12-01

    A positive family history is recognized as an important risk factor for type 2 diabetes mellitus (T2DM), but the association of family history with rennin-angiotensin system (RAS) gene polymorphisms has not been reported yet, thus we aim to investigate it.Family history records, clinical and biochemical data were obtained from 1239 T2DM patients. Polymerase chain reaction (PCR) was performed for angiotensin-converting enzyme (ACE) genotyping and PCR-restricted fragment length polymorphism was used for angiotensinogen (AGT) genotyping.Patients with a negative family history had higher level of triglyceride and blood pressure, whereas those with a positive family history showed younger onset age and lower body mass index value (All P history (All P history and those with a negative family history had comparable genotype and allele distribution of ACE gene insertion/deletion polymorphisms and AGT gene M/T polymorphisms.A positive family history of diabetes was not associated with the RAS gene polymorphisms. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  18. Local renin-angiotensin systems

    NARCIS (Netherlands)

    A.H.J. Danser (Jan)

    1992-01-01

    textabstractThe aim of this thesis was twofold. First, the regional metabolism and production of angiotensin I and angiotensin U were quantified in vivo in man and in anesthetized pigs. This was done by giving constant infusions of radiolabelect J25J-angiotensin I into either a peripheral vein

  19. Beneficial long-term effect of aldosterone antagonist added to a traditional blockade of the renin-angiotensin-aldosterone system among patients with obesity and proteinuria.

    Science.gov (United States)

    Morales, Enrique; Gutiérrez, Eduardo; Caro, Jara; Sevillano, Angel; Rojas-Rivera, Jorge; Praga, Manuel

    2015-01-01

    Over the past decade, obesity has become a risk factor for developing chronic kidney disease. Proteinuria is known to be an independent determinant of the progression of chronic kidney disease, and adipose tissue is a recognized source of components of the renin-angiotensin-aldosterone system (RAAS). Recent studies have shown that plasma aldosterone levels are disproportionately higher in patients with obesity. Drugs that block the RAAS are unable to inhibit aldosterone in the long term. The aim of our study was to analyze the renoprotective effect of an aldosterone antagonist in combination with RAAS blockers in patients with obesity and proteinuric nephropathy. This study is a substudy of previously published study on the renoprotective effect of mineralocorticoid receptor blockers in patients with proteinuric nephropathies. Patients with proteinuria levels >1g/24h who were taking spironolactone and were being treated with other RAAS blockers were divided according to body mass index (BMI) into an obesity group (BMI ≥30kg/m2) and a control group. Seventy-one patients were included in the study, with a mean age of 56.7±15.1 years. More than 50% of the patients in both groups had diabetes. Thirty-two patients were included in the obesity group and 39 were included in the control group. There were no significant differences in renal function, proteinuria, blood pressure, serum potassium levels and the percentage of RAAS blockers in both groups. After a follow-up of 28.9 (14-84) months, there was a 59.4% reduction in proteinuria in the obesity group (2.8±2.1 vs. 1.3±1.6g/24h, p<.05). The reduction in proteinuria was greater than 50% in 22 (68.8%) cases, and the mean blood pressure showed a significant decrease (from 100.6±9 to 92.1±7.4mm Hg, p<.05). The control group showed a 69.6% reduction in proteinuria (1.9±1.4 to 0.8±0.5, p<0.05). The reduction of proteinuria was higher than 50% in 22 (68.8%) cases in obese patients and in 33 (84.6%) cases in non

  20. Advances in understanding the renin-angiotensin-aldosterone system (RAAS in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Lama Ghazi

    2017-03-01

    Full Text Available The renin-angiotensin-aldosterone system (RAAS plays a fundamental role in the physiology of blood pressure control and the pathophysiology of hypertension (HTN with effects on vascular tone, sodium retention, oxidative stress, fibrosis, sympathetic tone, and inflammation. Fortunately, RAAS blocking agents have been available to treat HTN since the 1970s and newer medications are being developed. In this review, we will (1 examine new anti-hypertensive medications affecting the RAAS, (2 evaluate recent studies that help provide a better understanding of which patients may be more likely to benefit from RAAS blockade, and (3 review three recent pivotal randomized trials that involve newer RAAS blocking agents and inform clinical practice.

  1. High-intensity interval training has beneficial effects on cardiac remodeling through local renin-angiotensin system modulation in mice fed high-fat or high-fructose diets.

    Science.gov (United States)

    de Oliveira Sá, Guilherme; Dos Santos Neves, Vívian; de Oliveira Fraga, Shyrlei R; Souza-Mello, Vanessa; Barbosa-da-Silva, Sandra

    2017-11-15

    HIIT (high-intensity interval training) has the potential to reduce cardiometabolic risk factors, but the effects on cardiac remodeling and local RAS (renin-angiotensin system) in mice fed high-fat or high-fructose diets still need to be fully addressed. Sixty male C57BL/6 mice (12weeks old) were randomly divided into three groups, control (C), High-fat (HF), or High-fructose diet (HRU) and were monitored for eight weeks before being submitted to the HIIT. Each group was randomly assigned to 2 subgroups, one subgroup was started on a 12-week HIIT protocol (T=trained group), while the other subgroup remained non-exercised (NT=not-trained group). HIIT reduced BM and systolic blood pressure in high-fat groups, while enhanced insulin sensitivity after high-fat or high-fructose intake. Moreover, HIIT reduced left ventricular hypertrophy in HF-T and HFRU-T. Notably, HIIT modulated key factors in the local left ventricular renin-angiotensin-system (RAS): reduced protein expression of renin, ACE (Angiotensin-converting enzyme), and (Angiotensin type 2 receptor) AT2R in HF-T and HFRU-T groups but reduced (Angiotensin type 1 receptor) AT1R protein expression only in the high-fat trained group. HIIT modulated ACE2/Ang (1-7)/Mas receptor axis. ACE2 mRNA gene expression was enhanced in HF-T and HFRU-T groups, complying with elevated Mas (Mas proto-oncogene, G protein-coupled receptor) receptor mRNA gene expression after HIIT. This study shows the effectiveness of HIIT sessions in producing improvements in insulin sensitivity and mitigating LV hypertrophy, though hypertension was controlled only in the high-fat-fed submitted to HIIT protocol. Local RAS system in the heart mediates these findings and receptor MAS seems to play a pivotal role when it comes to the amelioration of cardiac structural and functional remodeling due to HIIT. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Effect of Losartan on Right Ventricular Dysfunction: Results From the Double-Blind, Randomized REDEFINE Trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) in Adults With Repaired Tetralogy of Fallot.

    Science.gov (United States)

    Bokma, Jouke P; Winter, Michiel M; van Dijk, Arie P; Vliegen, Hubert W; van Melle, Joost P; Meijboom, Folkert J; Post, Martijn C; Berbee, Jacqueline K; Boekholdt, S Matthijs; Groenink, Maarten; Zwinderman, Aeilko H; Mulder, Barbara J M; Bouma, Berto J

    2018-04-03

    The effect of angiotensin II receptor blockers on right ventricular (RV) function is still unknown. Angiotensin II receptor blockers are beneficial in patients with acquired left ventricular dysfunction, and recent findings have suggested a favorable effect in symptomatic patients with systemic RV dysfunction. The current study aimed to determine the effect of losartan, an angiotensin II receptor blocker, on subpulmonary RV dysfunction in adults after repaired tetralogy of Fallot. The REDEFINE trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) is an investigator-initiated, multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled study. Adults with repaired tetralogy of Fallot and RV dysfunction (RV ejection fraction [EF] 0.30 for all). In predefined subgroup analyses, losartan did not have a statistically significant impact on RV EF in subgroups with symptoms, restrictive RV, RV EFtetralogy of Fallot. Future larger studies may determine whether there might be a role for losartan in specific vulnerable subgroups. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02010905. © 2017 American Heart Association, Inc.

  3. Myeloperoxidase, asymmetric dimethyl-arginine and the renin-angiotensin-aldosterone-system in cardiovascular risk patients: Cross-sectional findings from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.

    Science.gov (United States)

    Zelzer, Sieglinde; Enko, Dietmar; Pilz, Stefan; Tomaschitz, Andreas; März, Winfried; Meinitzer, Andreas

    2017-09-01

    The leukocyte-derived myeloperoxidase (MPO), the nitric oxidase synthase (NOS) inhibitor asymmetrical dimethyl-arginine (ADMA) and the renin-angiotensin-aldosterone-system (RAAS) are associated with cardiovascular diseases (CVD). This study aimed to investigate potential interactions between the RAAS, ADMA and MPO in cardiovascular risk patients. All in all, 1446 patients, who were referred to coronary angiography, were included in this prospective study. MPO, ADMA and circulating serum markers of the RAAS system were measured. Additionally, all-cause and CVD mortality, cardiovascular risk factors, inflammatory and endothelial markers, and medication use were investigated. MPO concentrations were significantly associated with ADMA (P=0.002), renin (P=0.001) and angiotensin II levels (P=0.015), whereas ADMA was in tendency associated with renin (P=0.059) and significantly with angiotensin II (P=0.001). Both, ADMA and MPO were inversely correlated with angiotensinogen, angiotensin I and the angiotensin I/angiotensin II ratio. ADMA and angiotensin II were found stronger independent risk factors for all-cause and CVD mortality compared to MPO. MPO concentrations were significantly associated with higher ADMA levels and an up-regulated circulating RAAS in patients with CVD. Moreover, serum levels of ADMA and angiotensin II were shown to be more predictive for all-cause and CVD mortality compared to MPO. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  4. Myocardial fibrosis in patients with symptomatic obstructive hypertrophic cardiomyopathy: correlation with echocardiographic measurements, sarcomeric genotypes, and pro-left ventricular hypertrophy polymorphisms involving the renin-angiotensin-aldosterone system.

    Science.gov (United States)

    Blauwet, Lori A; Ackerman, Michael J; Edwards, William D; Riehle, Darren L; Ommen, Steve R

    2009-01-01

    Hypertrophic cardiomyopathy (HCM) is a heterogeneous disorder of the cardiac sarcomere, resulting in myocyte hypertrophy and disarray, interstitial fibrosis, and cardiac dysfunction. Our aim was to determine whether the amount of fibrosis in HCM correlates with echocardiographic measures of diastolic dysfunction, presence of HCM-susceptibility mutations, or polymorphisms in the renin-angiotensin-aldosterone system (RAAS). Surgical specimens from patients with obstructive HCM undergoing septal myectomy at the Mayo Clinic (2001-2004) were examined and compared with autopsy-derived tissues from age- and sex-matched normal controls. Digital image analysis was used to quantitate the fibrosis in representative microscopic sections. Genotyping was performed for myofilament-HCM using polymerase chain reaction, high-performance liquid chromatography, and direct DNA sequencing. RAAS polymorphism status was similarly established. The study included 59 HCM cases and 44 controls. Patients with HCM exhibited more fibrosis (mean 17%, range 3-45%) than controls (mean 8%, range 3-17%) (P or =1 C-encoding allele in CYP11B2-encoded aldosterone synthase. Patients with HCM undergoing septal myectomy had significantly more myocardial interstitial fibrosis than controls. The amount of fibrosis in HCM patients correlated with degree of septal hypertrophy and left ventricular systolic and diastolic function. Notably, neither mutations in cardiac myofilament proteins or polymorphisms in RAAS exhibited strong associations with severity of myocardial fibrosis.

  5. Renin-angiotensin-aldosterone genotype influences ventricular remodeling in infants with single ventricle.

    Science.gov (United States)

    Mital, Seema; Chung, Wendy K; Colan, Steven D; Sleeper, Lynn A; Manlhiot, Cedric; Arrington, Cammon B; Cnota, James F; Graham, Eric M; Mitchell, Michael E; Goldmuntz, Elizabeth; Li, Jennifer S; Levine, Jami C; Lee, Teresa M; Margossian, Renee; Hsu, Daphne T

    2011-05-31

    We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function, and response to enalapril in infants with single ventricle. Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with renin-angiotensin-aldosterone system upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate, and response to enalapril were compared between patients with ≥2 homozygous risk genotypes (high risk), and those with SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: Thirty-eight were high risk, and 116 were low risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and estimated glomerular filtration rate increased after SCPC in the low-risk (PSCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. Renin-angiotensin-aldosterone system genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume-unloading surgery. Follow-up is warranted to assess long-term impact. http://www.clinicaltrials.gov. Unique identifier: NCT00113087.

  6. Pioglitazone and the risk of cardiovascular events in patients with Type 2 diabetes receiving concomitant treatment with nitrates, renin-angiotensin system blockers, or insulin: results from the PROactive study (PROactive 20).

    Science.gov (United States)

    Erdmann, Erland; Spanheimer, Robert; Charbonnel, Bernard

    2010-09-01

    Patients with Type 2 diabetes mellitus (T2DM) are often treated with multiple glucose-lowering and cardiovascular agents. The concomitant use of nitrates, renin-angiotensin system (RAS) blockers, or insulin has been linked to a potential increase in myocardial ischemic risk with rosiglitazone. The PROactive database provides an opportunity to investigate the effects of these medications on the potential macrovascular benefits reported with pioglitazone. The PROactive study was a randomized double-blind prospective trial that evaluated mortality and cardiovascular morbidity in 5238 patients with T2DM and macrovascular disease. Patients received pioglitazone or placebo in addition to their baseline glucose-lowering and cardiovascular medications. The effect of pioglitazone on composite endpoints was evaluated, including all-cause death, myocardial infarction (MI), and stroke, as well as safety events of edema and serious heart failure, in subgroups using nitrates, RAS blockers, or insulin at baseline. The risk of all-cause death, MI, and stroke for pioglitazone versus placebo was similar regardless of the baseline use of nitrates, RAS blockers, or insulin, with hazard ratios ranging from 0.81 to 0.87. Similar results were obtained for the other composite endpoints analyzed. There were no significant interactions between baseline medication subgroups and treatment. The increased risk of edema and serious heart failure was consistent across the baseline medication subgroups. This post hoc analysis did not reveal an increased risk of macrovascular events with pioglitazone in patients receiving nitrates, RAS blockers, or insulin. Rather, all patients realized the same trend towards benefit with pioglitazone, and adverse events of edema and heart failure were predictable. © 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

  7. Urinary renin-angiotensin markers in polycystic kidney disease.

    Science.gov (United States)

    Salih, Mahdi; Bovée, Dominique M; Roksnoer, Lodi C W; Casteleijn, Niek F; Bakker, Stephan J L; Gansevoort, Ronald T; Zietse, Robert; Danser, A H Jan; Hoorn, Ewout J

    2017-10-01

    In autosomal dominant polycystic kidney disease (ADPKD), activation of the renin-angiotensin aldosterone system (RAAS) may contribute to hypertension and disease progression. Although previous studies have focused on circulating RAAS components, preliminary evidence suggests that APDKD may increase urinary RAAS components. Therefore, our aim was to analyze circulating and urinary RAAS components in ADPKD. We cross-sectionally compared 60 patients with ADPKD with 57 patients with non-ADPKD chronic kidney disease (CKD). The two groups were matched by sex, estimated glomerular filtration rate (eGFR), blood pressure, and RAAS inhibitor use. Despite similar plasma levels of angiotensinogen and renin, urinary angiotensinogen and renin excretion were five- to sixfold higher in ADPKD ( P kidney volume correlated with plasma renin and albuminuria but not with urinary renin or angiotensinogen excretions. Albuminuria correlated positively with urinary angiotensinogen and renin excretions in ADPKD and CKD. In three ADPKD patients who underwent nephrectomy, the concentrations of albumin and angiotensinogen were highest in plasma, followed by cyst fluid and urine; urinary renin concentrations were higher than cyst fluid. In conclusion, this study shows that, despite similar circulating RAAS component levels, higher urinary excretions of angiotensinogen and renin are a unique feature of ADPKD. Future studies should address the underlying mechanism and whether this may contribute to hypertension or disease progression in ADPKD. Copyright © 2017 the American Physiological Society.

  8. Angiotensin receptor blockers are associated with lower mortality than ACE inhibitors in predialytic stage 5 chronic kidney disease: A nationwide study of therapy with renin-angiotensin system blockade.

    Directory of Open Access Journals (Sweden)

    Chih-Ching Lin

    Full Text Available Dual renin angiotensin system (RAS blockade using angiotensin-receptor blockers (ARBs in combination with angiotensin converting enzyme inhibitors (ACEIs is reported to improve proteinuria in both diabetic and non-diabetic patients. However, its renoprotective effect and safety remain uncertain in patients with advanced chronic kidney disease (CKD. From January 1, 2000 through June 30, 2009, we enrolled 14,117 pre-dialytic stage 5 CKD patients with serum creatinine >6mg/dL and hematocrit <28% under the treatment with erythropoiesis stimulating agents and RAS blockade. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs against the commencement of long-term dialysis and all-cause mortality for ACEI/ARB users. Over a median follow-up of 7 months, 9,867 patients (69.9% required long-term dialysis and 2,805 (19.9% died before progression to end-stage renal disease requiring dialysis. In comparison with the ARB-only users, dual blockade with ACEIs and ARBs was associated with a significantly higher risk of (1 death in all CKD patients (HR = 1.49, [95%CI, 1.30-1.71]; P = 0.02 and in diabetic subgroup (HR = 1.58, [95%CI, 1.34-1.86]; P = 0.02; (2 composite endpoint of long-term dialysis or death in diabetic subgroup (HR = 1.10, [95%CI, 1.01-1.20]; P = 0.04; (3 hyperkalemia-associated hospitalization in non-diabetic subgroup (HR, 2.74, [95%CI, 1.05-7.15]; P = 0.04. However, ACEIs users were associated with higher mortality than ARBs users in all CKD patients (HR = 1.17, [95%CI, 1.07-1.27]; P = 0.03 and in diabetic subgroup (HR = 1.32, [95%CI, 1.18-1.48]; P = 0.03. Monotherapy of RAS blockade, especially ARB, is more effective and safer than dual RAS blockade in pre-dialytic stage 5 CKD patients.

  9. Venous responses during exercise in rainbow trout, Oncorhynchus mykiss : [alpha]-adrenergic control and the antihypotensive function of the renin-angiotensin system

    DEFF Research Database (Denmark)

    Sandblom, E.; Axelsson, M.; McKenzie, David

    2006-01-01

    The role of the [alpha]-adrenergic system in the control of cardiac preload (central venous blood pressure; Pven) and venous capacitance during exercise was investigated in rainbow trout (Oncorhynchus mykiss). In addition, the antihypotensive effect of the renin-angiotesin system (RAS) was invest...

  10. Venous responses during exercise in rainbow trout, Oncorhynchus mykiss : [alpha]-adrenergic control and the antihypotensive function of the renin-angiotensin system

    DEFF Research Database (Denmark)

    Sandblom, E.; Axelsson, M.; McKenzie, David

    2006-01-01

    The role of the [alpha]-adrenergic system in the control of cardiac preload (central venous blood pressure; Pven) and venous capacitance during exercise was investigated in rainbow trout (Oncorhynchus mykiss). In addition, the antihypotensive effect of the renin-angiotesin system (RAS...... trout. It is also the first study to suggest that the RAS may be an important modulator of venous pressure and capacitance in fish....

  11. QGQS Granule in SHR Serum Metabonomics Study Based on Tools of UPLC-Q-TOF and Renin-Angiotensin-Aldosterone System Form Protein Profilin-1

    Directory of Open Access Journals (Sweden)

    Ke Li

    2017-01-01

    Full Text Available QGQS granule is effective for the therapeutic of hypertension in clinic. The aim of this research is to observe the antihypertension effect of QGQS granule on SHR and explain the mechanism of its lowering blood pressure. 30 SHR were selected as model group, captopril group, and QGQS group, 10 WKYr were used as control group, and RBP were measured on tail artery consciously. And all the serum sample analysis was carried out on UPLC-TOF-MS system to determine endogenous metabolites and to find the metabonomics pathways. Meanwhile, ELISA kits for the determination pharmacological indexes of PRA, AngI, AngII, and ALD were used for pathway confirmatory; WB for determination of profilin-1 protein expression was conducted for Ang II pathway analysis as well. It is demonstrated that QGQS granule has an excellent therapeutic effect on antihypertension, which exerts effect mainly on metabonomics pathway by regulating glycerophospholipid, sphingolipid, and arachidonic acid metabolism, and it could inhibit the overexpression of the profilin-1 protein. We can come to a conclusion that RAAS should be responsible mainly for the metabonomics pathway of QGQS granule on antihypertension, and it plays a very important role in protein of profilin-1 inhibition.

  12. Anti-stress and nootropic activity of drugs affecting the renin-angiotensin system in rats based on indirect biochemical evidence.

    Science.gov (United States)

    Anil Kumar, K V; Nagwar, Shrasti; Thyloor, Rama; Satyanarayana, Sreemantula

    2015-12-01

    Various stress hormones are responsible for bringing out stress-related changes and are implicated in learning and memory processes. The extensive clinical experience of angiotensin receptor blockers (ARBs) and direct renin inhibitor as antihypertensive agents provides anecdotal evidence of improvements in cognition. The neurochemical basis underlying the anti-stress and nootropic effects are unclear. This study was aimed to determine the effects of aliskiren, valsartan and their combination on the neuromediators of the central nervous system (CNS) and periphery as well as on cognitive function. Groups of rats were subjected to a forced swim stress for one hour after daily treatment with aliskiren, valsartan and their combination. The 24 h urinary excretion of vanillylmandellic acid (VMA), 5-hydroxyindoleacetic acid (5-HIAA), 6-β-hydroxycortisol (6-β-OH) cortisol and homovanillic acid (HVA) was determined in all groups under normal and stressed conditions. Nootropic activity was studied using cook's pole climbing apparatus and acetylcholinesterase (AChE) inhibitory activity by Ellman's method. Administration of aliskiren (10 mg/kg), valsartan (20 mg/kg) and their combination at a dose of 5 and 10 mg/kg respectively reduced the urinary metabolite levels. Further, all drugs showed significant improvement in scopolamine-impaired performance and produced inhibition of the AChE enzyme. The present study provides scientific support for the anti-stress and nootropic activities of aliskiren, valsartan and their combination. © The Author(s) 2014.

  13. Renin-angiotensin-aldosterone responsiveness to low sodium and blood pressure reactivity to angiotensin-II are unrelated to cholesteryl ester transfer protein mass in healthy subjects

    NARCIS (Netherlands)

    Krikken, Jan A.; Dallinga-Thie, Geesje M.; Navis, Gerjan; Dullaart, Robin P. F.

    2008-01-01

    BACKGROUND: The blood pressure increase associated with the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib is probably attributable to an off-target effect but it is unknown whether activation of the renin-angiotensin-aldosterone system (RAAS) may be related to variation in the

  14. MicroRNA in Diabetic Nephropathy: Renin Angiotensin, AGE/RAGE, and Oxidative Stress Pathway

    Directory of Open Access Journals (Sweden)

    Shinji Hagiwara

    2013-01-01

    Full Text Available MicroRNAs (miRNA are a novel class of small, noncoding RNA molecules that have gained the attention of many researchers in recent years due to their ability to posttranscriptionally regulate the expression of families of genes simultaneously. Their role in normal physiology and pathobiology is intriguing and their regulation in normal and disease states is fascinating. That the cells can return to a state of homeostasis when these small molecules are perturbed is truly remarkable given the multiple cellular targets of each miRNA and that many mRNAs are targeted by multiple miRNAs. Several reviews have covered aspects of miRNA function in biology and disease. Here, we review the role of miRNA in regulating the renin-angiotensin system, AGE/RAGE signalling, and under conditions of oxidative stress in the context of diabetic nephropathy.

  15. Comparison of the antialbuminuric effects of benidipine and hydrochlorothiazide in Renin-Angiotensin System (RAS) inhibitor-treated hypertensive patients with albuminuria: the COSMO-CKD (COmbination Strategy on Renal Function of Benidipine or Diuretics TreatMent with RAS inhibitOrs in a Chronic Kidney Disease Hypertensive Population) study.

    Science.gov (United States)

    Ando, Katsuyuki; Nitta, Kosaku; Rakugi, Hiromi; Nishizawa, Yoshiki; Yokoyama, Hitoshi; Nakanishi, Takeshi; Kashihara, Naoki; Tomita, Kimio; Nangaku, Masaomi; Takahashi, Katsutoshi; Isshiki, Masashi; Shimosawa, Tatsuo; Fujita, Toshiro

    2014-01-01

    This study evaluated the non-inferiority of renoprotection afforded by benidipine versus hydrochlorothiazide in hypertensive patients with chronic kidney disease (CKD). In this prospective, multicenter, open-labeled, randomized trial, the antialbuminuric effects of benidipine and hydrochlorothiazide were examined in renin-angiotensin system (RAS) inhibitor-treated patients with blood pressure (BP) readings of ≥ 130/80 mmHg and ≤ 180/110 mmHg, a urinary albumin to creatinine ratio (UACR) of ≥ 300 mg/g, and an estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73m(2). Patients received benidipine (n = 176, final dose: 4.8 mg/day) or hydrochlorothiazide (n = 170, 8.2 mg/day) for 12 months. Benidipine and hydrochlorothiazide exerted similar BP- and eGFR-decreasing actions. The UACR values for benidipine and hydrochlorothiazide were 930.8 (95% confidence interval: 826.1, 1048.7) and 883.1 (781.7, 997.7) mg/g at baseline, respectively. These values were reduced to 790.0 (668.1, 934.2) and 448.5 (372.9, 539.4) mg/g at last observation carried forward (LOCF) visits. The non-inferiority of benidipine versus hydrochlorothiazide was not demonstrated (benidipine/hydrochlorothiazide ratio of LOCF value adjusted for baseline: 1.67 (1.40, 1.99)). The present study failed to demonstrate the non-inferiority of the antialbuminuric effect of benidipine relative to that of hydrochlorothiazide in RAS inhibitor-treated hypertensive patients with macroalbuminuria.

  16. Salt-Sensitive Hypertension: Perspectives on Intrarenal Mechanisms

    Science.gov (United States)

    Majid, Dewan S.A.; Prieto, Minolfa C.; Navar, L Gabriel

    2015-01-01

    Salt sensitive hypertension is characterized by increases in blood pressure in response to increases in dietary salt intake and is associated with an enhanced risk of cardiovascular and renal morbidity. Although researchers have sought for decades to understand how salt sensitivity develops in humans, the mechanisms responsible for the increases in blood pressure in response to high salt intake are complex and only partially understood. Until now, scientists have been unable to explain why some individuals are salt sensitive and others are salt resistant. Although a central role for the kidneys in the development of salt sensitivity and hypertension has been generally accepted, it is also recognized that hypertension is of multifactorial origin and a variety of factors can induce, or prevent, blood pressure responsiveness to the manipulation of salt intake. Excess salt intake in susceptible persons may also induce inappropriate central and sympathetic nervous system responses and increase the production of intrarenal angiotensin II, catecholamines and other factors such as oxidative stress and inflammatory cytokines. One key factor is the concomitant inappropriate or paradoxical activation of the intrarenal renin-angiotensin system, by high salt intake. This is reflected by the increases in urinary angiotensinogen during high salt intake in salt sensitive models. A complex interaction between neuroendocrine factors and the kidney may underlie the propensity for some individuals to retain salt and develop salt-dependent hypertension. In this review, we focus mainly on the renal contributions that provide the mechanistic link between chronic salt intake and the development of hypertension. PMID:26028244

  17. Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers.

    Science.gov (United States)

    Heerspink, H J L; Johnsson, E; Gause-Nilsson, I; Cain, V A; Sjöström, C D

    2016-06-01

    To characterize the effect of dapagliflozin on albuminuria and estimated glomerular filtration rate (eGFR) and to determine whether effects on albuminuria were mediated through changes in glycated haemoblogin (HbA1c), systolic blood pressure (SBP), body weight or eGFR. We conducted a post hoc analysis of data pooled from two phase III clinical trials in hypertensive patients with type 2 diabetes (T2DM) on stable angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, randomly assigned to dapagliflozin 10 mg/day or matched placebo. This analysis included only patients with microalbuminuria or macroalbuminuria at baseline. Patients were randomized to receive dapagliflozin 10 mg (n = 167) or placebo (n = 189). Dapagliflozin resulted in greater 12-week reductions in albuminuria compared with placebo: -33.2% [95% confidence interval (CI) -45.4, -18.2]. The reduction in albuminuria was also present after adjusting for age, sex and changes in HbA1c, SBP, body weight and eGFR: -23.5% (95% CI -37.6, -6.3). There was a decrease in eGFR with dapagliflozin versus placebo that was readily reversed 1 week after last dose. No serious renal-related adverse events were observed in any group. Dapagliflozin was effective in lowering albuminuria in patients with T2DM and hypertension using renin-angiotensin system blockade therapy. Reductions in albuminuria were still present after adjusting for changes in HbA1c, SBP, body weight and eGFR. Dapagliflozin-induced improvements in glycaemic control and reductions in SBP, coupled with other potentially beneficial renal effects, may lead to a reduced long-term renal and cardiovascular risk. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  18. Renin-angiotensin system blockade alone or combined with ETA receptor blockade: effects on the course of chronic kidney disease in 5/6 nephrectomized Ren-2 transgenic hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Sedláková, L.; Čertíková; Chábová, V.; Doleželová, Š.; Škaroupková, P.; Kopkan, L.; Husková, Z.; Červenková, L.; Kikerlová, S.; Vaněčková, Ivana; Sadowski, J.; Kompanowska; Jezierska, E.; Kujal, P.; Kramer, H. J.; Červenka, L.

    2017-01-01

    Roč. 39, č. 2 (2017), s. 183-195 ISSN 1064-1963 Institutional support: RVO:67985823 Keywords : chronic kidney disease * endothelin system * hypertension * renin–angiotensin system * 5/6 nephrectomy Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Cardiac and Cardiovascular systems Impact factor: 1.162, year: 2016

  19. Dual renin-angiotensin system blockade plus oral methylprednisone for the treatment of proteinuria in IgA nephropathy Doble bloqueo del sistema renina-angiotensina más metilprednisona oral para el tratamiento de la proteinuria en la nefropatía por IgA

    Directory of Open Access Journals (Sweden)

    Hernán Trimarchi

    2007-10-01

    Full Text Available Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria > 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 ± 13.26 years (50% male; 7 patients (35% were hypertensive; proteinuria 2.2 ± 1.86 g/day; serum creatinine 1.07 ± 0.29 mg/dl; mean follow-up 60.10 ± 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60% were class II; seven (35% were class III and one (5% class V. All patients received dual reninangiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 ± 0.07 g/day (P El doble bloqueo del sistema renina-angiotensina con inhibidores de la enzima convertidora de angiotensina junto a bloqueadores del receptor tipo I de angiotensina II es aceptado como tratamiento en la proteinuria de la nefropatía por IgA, ya que el rol de los inmunosupresores continúa siendo controvertido. Estudio prospectivo, no controlado, abierto para pacientes con nefropatía por IgA con proteinurias >0.5 g/día y creatininas séricas <1.4 mg/dl, para evaluar la eficacia de tratamiento de enalapril más valsartán asociado a metilprednisona vía oral para disminuir las proteinurias a <0.5 g

  20. Lipids, inflammation, and the Renin-Angiotensin System

    NARCIS (Netherlands)

    Harst, Pim van der

    2006-01-01

    Summary and Future Perspectives Impaired endothelial function is recognized as one of the earliest events of atherogenesis.1, 2 In Part I, chapter 1, we discussed the clinical value of the different techniques to evaluate endothelium-dependent vasomotor function. We also reviewed the efficacy of

  1. Effect of Dual Blockade of Renin-Angiotensin Aldosterone System ...

    African Journals Online (AJOL)

    Purpose: To investigate the dual effect of angiotensin blockade by irbesartan and enalapril on proteinuria in diabetic patients with azotemia. Methods: Patients with diabetes of > 5 years duration, proteinuria at a nephrotic level and serum creatinine > 1.5 mg/dL were enrolled in the study. Forty-five enrolled patients were ...

  2. Renin-angiotensin system in human coronavirus pathogenesis

    NARCIS (Netherlands)

    Wevers, Brigitte A.; van der Hoek, Lia

    2010-01-01

    Although initially considered relatively harmless pathogens, human coronaviruses (HCoVs) are nowadays known to be associated with more severe clinical complications. Still, their precise pathogenic potential is largely unknown, particularly regarding the most recently identified species HCoV-NL63

  3. Renal Impairment: Drugs, Radiocontrast Media and Renin-Angiotensin System

    Directory of Open Access Journals (Sweden)

    José Antonio Chipi Cabrera

    2014-12-01

    Full Text Available Continuous population aging, coupled with increased prevalence of chronic noncommunicable diseases, particularly diabetes mellitus and hypertension as major causes of impaired renal function, has led to the introduction of new and more powerful drugs for the prevention and treatment of these conditions over the years. This entails an updated knowledge of the pharmacokinetics of these drugs to prevent possible toxic effects, which involves a preliminary assessment of the renal function prior to the introduction of any potentially nephrotoxic substance. The ultimate expression of this nephrotoxicity is hospital-acquired or community-acquired acute renal failure caused by a therapeutic error due to drug misuse in elderly patients with multiple risk factors or pre-existing impaired renal function. The aim of this literature review is to provide health professionals with an abridged and updated vision of the pathophysiological mechanisms related to nephrotoxicity and in turn provide the necessary tools for dose adjustment according to the patient’s renal function.

  4. Renin-angiotensin-aldosterone-blockade is associated with decreased use of antidepressant therapy in patients with type 1 diabetes and diabetic nephropathy.

    Science.gov (United States)

    Ahola, Aila J; Harjutsalo, Valma; Forsblom, Carol; Groop, Per-Henrik

    2014-08-01

    Hypertension and depression are frequent comorbidities of diabetes. Studies suggest that antihypertensive medication affecting the renin-angiotensin-aldosterone system (RAAS) might also relieve depression. Whether this is also seen in patients with type 1 diabetes is not known. We therefore studied whether use of RAAS-modifying medication is associated with reduced antidepressant use in type 1 diabetes. In all, 1,705 participants in the FinnDiane Study were included (57 % men, mean age 46 ± 11 years). Data on medications were obtained from the Drug Prescription Register. Based on their albumin excretion rate (AER), the patients were classified as having normal AER, microalbuminuria, or macroalbuminuria. Diabetic nephropathy was defined as macroalbuminuria or end-stage renal disease (dialysis or renal transplant). A total of 8.4 and 10.9 % of patients with and without RAAS-modifying medication, respectively, had antidepressant medication purchases (NS). In logistic regression analysis, after adjusting for potential confounding factors, use of RAAS-modifying medication was not associated with antidepressant purchases. However, when patients with and without diabetic nephropathy were analyzed separately, RAAS-modifying medication was associated with lower frequency of antidepressant purchases among patients with established diabetic nephropathy. In conclusion, use of RAAS-modifying medication may improve mood in patients with type 1 diabetes and established diabetic nephropathy.

  5. Serum levels of renin, angiotensin-converting enzyme and angiotensin II in patients treated by surgical excision, propranolol and captopril for problematic proliferating infantile haemangioma.

    Science.gov (United States)

    Sulzberger, L; Baillie, R; Itinteang, T; de Jong, S; Marsh, R; Leadbitter, P; Tan, S T

    2016-03-01

    The role of the renin-angiotensin system (RAS) in the biology of infantile haemangioma (IH) and its accelerated involution induced by β-blockers was first proposed in 2010. This led to the first clinical trial in 2012 using low-dose captopril, an angiotensin-converting enzyme (ACE) inhibitor, demonstrating a similar response in these tumours. This study aimed to compare serial serum levels of the components of the RAS in patients before and after surgical excision, propranolol or captopril treatment for problematic proliferating IH. Patients with problematic proliferating IH underwent measurements of serum levels of plasma renin activity (PRA), ACE and angiotensin II (ATII) before, and 1-2 and 6 months following surgical excision, propranolol or captopril treatment. This study included 27 patients undergoing surgical excision (n = 8), propranolol (n = 11) and captopril (n = 8) treatment. Treatment with either surgical excision or propranolol resulted in significant decrease in the mean levels of PRA. Surgical excision or captopril treatment led to significant decline in the mean levels of ATII. All three treatment modalities had no significant effect on the mean levels of ACE. This study demonstrates the effect of surgical excision, propranolol and captopril treatment in lowering the levels of PRA and ATII, but not ACE, supporting a mechanistic role for the RAS in the biology of IH. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  6. Prenatal Exposure to LPS Alters The Intrarenal RAS in Offspring, Which Is Ameliorated by Adipose Tissue-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Ding, Xian-Fei; Sun, Mou; Guan, Fang-Xia; Guo, Li-Na; Zhang, Yan-Yan; Wan, You-Dong; Zhang, Xiao-Juan; Yu, Yan-Wu; Ma, Shan-Shan; Yao, Hai-Mu; Yao, Rui; Zhang, Rui-Fang; Sun, Tong-Wen; Kan, Quan-Cheng

    2017-11-06

    Prenatal lipopolysaccharide (LPS) exposure causes hypertension in rat offspring through an unknown mechanism. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) in hypertension induced by prenatal LPS exposure and also explored whether adipose tissue-derived mesenchymal stem cells (ADSCs) can ameliorate the effects of prenatal LPS exposure in rat offspring. Sixty-four pregnant rats were randomly divided into 4 groups (n = 16 in each), namely, a control group and an LPS group, which were intraperitoneally injected with vehicle and 0.79 mg/kg LPS, respectively, on the 8th, 10th, and 12th days of gestation; an ADSCs group, which was intravenously injected with 1.8 × 107 ADSCs on the 8th, 10th, and 12th days of gestation; and an LPS + ADSCs group, which received a combination of the treatments administered to the LPS and ADSCs groups. Prenatal LPS exposure increased blood pressure, Ang II expression, Ang II-positive, monocyte and lymphocyte, apoptotic cells in the kidney, and induced renal histological changes in offspring; however, the LPS and control groups did not differ significantly with respect to plasma renin activity levels, Ang II levels, or renal function. ADSCs treatment attenuated the blood pressure and also ameliorated the other effects of LPS-treated adult offspring. Prenatal exposure to LPS activates the intrarenal RAS but not the circulating RAS and thus induces increases in blood pressure in adult offspring; however, ADSCs treatment attenuates the blood pressure increases resulting from LPS exposure and also ameliorates the other phenotypic changes induced by LPS treatment by inhibiting intrarenal RAS activation. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  7. Intrarenal hemodynamics and impaired tubular functions in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    A N Maksudova

    2010-01-01

    Conclusion. The smaller and no RFR in patients without signs of nephropathy may suggest occult intrarenal hemodynamic disorders detected during the dopamine stress test. Tubular impairments in SLE were largely characteristic of patients with intrarenal hemodynamic disorders.

  8. Risk factors of systemic inflammation response syndrome after endoscopic combined intrarenal surgery in the modified Valdivia position.

    Science.gov (United States)

    Tabei, Tadashi; Ito, Hiroki; Usui, Kimitsugu; Kuroda, Shinnosuke; Kawahara, Takashi; Terao, Hideyuki; Fujikawa, Atsushi; Makiyama, Kazuhide; Yao, Masahiro; Matsuzaki, Junichi

    2016-08-01

    To identify risk factors of developing systemic inflammation response syndrome after endoscopic combined intrarenal surgery in the modified Valdivia position for renal stone treatment. We retrospectively analyzed 370 consecutive patients who underwent endoscopic combined intrarenal surgery procedures in the modified Valdivia position to treat renal stones. Antibiotic therapy based on preoperative urine cultures was administered to all patients from induction of anesthesia until at least postoperative day 3. Postoperative systemic inflammation response syndrome was diagnosed if the patient met two or more systemic inflammation response syndrome criteria. A multivariate logistic regression model with backward selection was used to evaluate the relationships between the incidence of systemic inflammation response syndrome after endoscopic combined intrarenal surgery and other clinical factors. Of the 370 patients, 61 patients (16.5%) were diagnosed with systemic inflammation response syndrome after endoscopic combined intrarenal surgery. Significant differences were found between the non-systemic inflammation response syndrome and systemic inflammation response syndrome groups with regard to female sex (29.8% vs 44.3%, P = 0.027), history of febrile urinary tract infection (16.5% vs 32.8%, P = 0.015) and number of involved calyces (2.68 vs 4.1, P systemic inflammation response syndrome: the number of involved calyces (P = 0.017), stone surface area (P = 0.021) and history of febrile urinary tract infection (P = 0.005). The number of involved calyces larger than four, stone surface area >500 mm(2) and a history of febrile urinary tract infection independently predicted the development of systemic inflammation response syndrome after endoscopic combined intrarenal surgery. This is the first study to identify the independent predictors of systemic inflammation response syndrome after endoscopic combined intrarenal surgery in the modified Valdivia position. © 2016 The

  9. Dog kidney: anatomical relationships between intrarenal arteries and kidney collecting system.

    Science.gov (United States)

    Marques-Sampaio, Beatriz P S; Pereira-Sampaio, Marco A; Henry, Robert W; Favorito, Luciano A; Sampaio, Francisco J B

    2007-08-01

    The detailed findings of canine intrarenal anatomy (collecting system and arteries) are presented. Ninety-five three-dimensional endocasts of the kidney collecting system together with the intrarenal arteries were prepared using standard injection-corrosion techniques and were studied. A single renal artery was observed in 88.4% of the casts. The renal artery divided into a dorsal and a ventral branch. Using the branching pattern of the ventral and dorsal divisions of the renal artery, the vessels were classified in type I or type II. Type I presented a cranial and a caudal artery, whereas type II presented a mesorenal and a caudal artery. Cranial branches of dorsal and ventral arteries supplied the cranial pole in 90.5% of the specimens. Caudal branches of the dorsal and the ventral divisions of the renal artery irrigated both the caudal pole and the mid-zone of the kidney in 95.8% and 98.9% of the cases, respectively. In all casts, caudal branches of both dorsal and ventral arteries supplied the caudal pole. Therefore, the caudal branches of the ventral and dorsal divisions of the renal artery are of utmost importance in the kidney arterial supply. Although many results of renal and intrarenal anatomy in dogs may not be completely transposed to humans, the anatomical relationship between arteries and the collecting system in the cranial pole of the dog kidney is similar to those in man. This fact supports the use of the dog as an animal model for urologic procedures at the cranial pole. (c) 2007 Wiley-Liss, Inc.

  10. The renin-angiotensin-aldosterone system in cerebral small vessel disease

    NARCIS (Netherlands)

    Brenner, D.; Labreuche, J.; Pico, F.; Scheltens, P.; Poirier, O.; Cambien, F.; Amarenco, P.

    2008-01-01

    Introduction: Cerebral small vessel disease (SVD) appears on magnetic resonance imaging (MRI) as leukoaraiosis (LA), état criblé (EC), and multiple lacunar infarctions (MLI). Although the pathophysiology of SVD is poorly understood, there is evidence of a genetic contribution. We sought to analyze

  11. Role of the renin-angiotensin system in regulation and autoregulation of renal blood flow

    DEFF Research Database (Denmark)

    Sørensen, Charlotte Mehlin; Leyssac, Paul Peter; Skøtt, Ole

    2000-01-01

    The role for ANG II in renal blood flow (RBF) autoregulation is unsettled. The present study was designed to test the effect of clamping plasma ANG II concentrations ([ANG II]) by simultaneous infusion of the angiotensin-converting enzyme inhibitor captopril and ANG II on RBF autoregulation...

  12. Introductory statement: Of receptors and analogs in renin-angiotensin-aldosterone and adrenergic systems

    International Nuclear Information System (INIS)

    Eliahou, H.E.; Iaina, A.

    1980-01-01

    This article reports on the role of the octapeptides angiotensin II (A II)-effector and its receptor on hypertensive patients and in animal experiments. By applying the A-II-receptor blockers, vasodilates drugs, β-receptor blockers and by sodium depletion, the behaviour of the blood pressure, the plasmareninactivity, and of the aldosteron were investigated; a comparative investigation between the A II and A III effectors was also carried out. The iodo-hippurate uptake was reduced with an artificially produced renal arterial ischemia. In general, this investigation provided new viewpoints in the understanding of the possible pathogenetic mechanism of essential hypertonism. (APR) [de

  13. Urinary albumin excretion and the renin-angiotensin system in cardiovascular risk management

    NARCIS (Netherlands)

    Van de Wal, R. M. A.; Voors, A. A.; Gansevoort, R. T.

    2006-01-01

    Microalbuminuria has been shown to be a strong predictor of cardiovascular morbidity and mortality in diabetic and hypertensive patients, but also in the general population. Moreover, several reports suggest that reduction of urinary albumin excretion (UAE) is associated with improvement of

  14. Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin system

    Science.gov (United States)

    Jacob, G.; Robertson, D.; Mosqueda-Garcia, R.; Ertl, A. C.; Robertson, R. M.; Biaggioni, I.

    1997-01-01

    PURPOSE: Orthostatic intolerance is the cause of significant disability in otherwise normal patients. Orthostatic tachycardia is usually the dominant hemodynamic abnormality, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety and, in some cases, syncope. It is the most common disorder of blood pressure regulation after essential hypertension. There is a predilection for younger rather than older adults and for women more than men. Its cause is unknown; partial sympathetic denervation or hypovolemia has been proposed. METHODS AND MATERIALS: We tested the hypothesis that reduced plasma renin activity, perhaps from defects in sympathetic innervation of the kidney, could underlie a hypovolemia, giving rise to these clinical symptoms. Sixteen patients (14 female, 2 male) ranging in age from 16 to 44 years were studied. Patients were enrolled in the study if they had orthostatic intolerance, together with a raised upright plasma norepinephrine (> or = 600 pg/mL). Patients underwent a battery of autonomic tests and biochemical determinations. RESULTS: There was a strong positive correlation between the blood volume and plasma renin activity (r = 0.84, P = 0.001). The tachycardic response to upright posture correlated with the severity of the hypovolemia. There was also a correlation between the plasma renin activity measured in these patients and their concomitant plasma aldosterone level. CONCLUSIONS: Hypovolemia occurs commonly in orthostatic intolerance. It is accompanied by an inappropriately low level of plasma renin activity. The degree of abnormality of blood volume correlates closely with the degree of abnormality in plasma renin activity. Taken together, these observations suggest that reduced plasma renin activity may be an important pathophysiologic component of the syndrome of orthostatic intolerance.

  15. Dual renin-angiotensin system blockade at optimal doses for proteinuria

    NARCIS (Netherlands)

    Laverman, GD; Navis, G; Henning, RH; de Jong, PE; dE Zeeuw, D

    Background. The antiproteinuric effect of combining the angiotensin-converting enzyme (ACE) inhibitor lisinopril and the angiotensin II (Ang II) antagonist losartan was compared to that of the optimal antiproteinuric doses of monotherapy. Methods. To this purpose, lisinopril and losartan were

  16. Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis

    DEFF Research Database (Denmark)

    Gribouval, Olivier; Morinière, Vincent; Pawtowski, Audrey

    2012-01-01

    Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuri...

  17. Renin-angiotensin system antagonists and clinical outcomes in stable coronary artery disease without heart failure.

    Science.gov (United States)

    Sorbets, Emmanuel; Labreuche, Julien; Simon, Tabassome; Delorme, Laurent; Danchin, Nicolas; Amarenco, Pierre; Goto, Shinya; Meune, Christophe; Eagle, Kim A; Bhatt, Deepak L; Steg, Philippe Gabriel

    2014-07-01

    The aim of this study was to determine whether angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II receptor blocker (ARB) use is associated with lower rates of cardiovascular events in patients with stable coronary artery disease (CAD) but without heart failure (HF) receiving contemporary medical management. Using data from the Reduction of Atherothrombosis for Continued Health (REACH) registry, we examined, using propensity score approaches, relationships between cardiovascular outcomes and ACEI/ARB use (64.1% users) in 20 909 outpatients with stable CAD and free of HF at baseline. As internal control, we assessed the relation between statin use and outcomes. At 4-year follow-up, the risk of cardiovascular death, MI, or stroke (primary outcome) was similar in ACEI/ARB users compared with non-users (hazard ratio, 1.03; 95% confidence interval [CI], 0.91-1.16; P = 0.66). Similarly, the risk of the primary outcome and cardiovascular hospitalization for atherothrombotic events (secondary outcome) was not reduced in ACEI/ARB users (hazard ratio, 1.08; 95% CI, 1.01-1.16; P = 0.04), nor were the rates of any of its components. Analyses using propensity score matching yielded similar results, as did sensitivity analyses accounting for missing covariates, changes in medications over time, or analysing separately ACEI and ARB use. In contrast, in the same cohort, statin use was associated with lower rates for all outcomes. Use of ACEI/ARB was not associated with better outcomes in stable CAD outpatients without HF. The benefit of ACEI/ARB seen in randomized clinical trials was not replicated in this large contemporary cohort, which questions their value in this specific subset. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  18. Does renin-angiotensin system blockade have a role in preventing diabetic retinopathy? A clinical review

    DEFF Research Database (Denmark)

    Sjølie, A K; Dodson, P; Hobbs, F R R

    2011-01-01

    Diabetes management has increasingly focused on the prevention of macrovascular disease, in particular for type 2 diabetes. Diabetic retinopathy, one of the main microvascular complications of diabetes, is also an important public health problem. Much of the care invested in retinopathy relates...... the primary trial end-points were not met, there was a clear trend to less severe retinopathy with RAS blockade. A smaller trial, RASS, reported reduced retinopathy progression in type 1 diabetes from RAS blockade with both the ARB losartan and the angiotensin converting enzyme (ACE) inhibitor enalapril...

  19. Renin-angiotensin system gene polymorphisms and high blood pressure in Lithuanian children and adolescents.

    Science.gov (United States)

    Simonyte, Sandrita; Kuciene, Renata; Medzioniene, Jurate; Dulskiene, Virginija; Lesauskaite, Vaiva

    2017-09-13

    Epidemiological studies have demonstrated the influence of environmental factors on HBP in the population of Lithuanian children, although the role of genetic factors in hypertension has not yet been studied. The aim of this study was to assess the distribution of AGTR1, AGT, and ACE genotypes in the Lithuanian child population and to determine whether these genotypes have an impact on HBP in childhood. This cross-sectional study enrolled 709 participants aged 12-15 years. The subjects were genotyped for AGT (M235 T, rs699), AGTR1 (A1166C, rs5186), and ACE (rs4340) gene polymorphisms using real-time and conventional polymerase chain reactions. Blood pressure and anthropometric parameters were measured. The prevalence of HBP was 38.6% and was more frequently detected in boys than in girls (47.9% vs. 29.5%; p < 0.001). No significant differences in the frequencies of the AGT or AGTR1 genotypes or alleles between boys and girls were observed, except for ACE genotypes. The mean SBP value was higher in HBP subjects with ACE ID genotype compared to those with ACE II homozygotes (p = 0.04). No significant differences in BP between different AGT and AGTR1 genotype groups were found. Boys who carried the ACE ID + DD genotypes had higher odds of having HBP than carriers of the ACE II genotype did (controlling for the body mass index (BMI): OR MH  = 1.83; 95% CI, 1.11-3.02, p = 0.024; and controlling for waist circumference (WC): OR MH  = 1.76; 95% CI, 1.07-2.92, p = 0.035). These associations were not significant among girls. The same trend was observed in the multivariate analysis - after adjustment for BMI and WC, only boys with ACE ID genotype and ACE ID + DD genotypes had statistically significantly increased odds of HBP (aOR = 2.05; 95% CI, 1.19-3.53 (p = 0.01) and aOR = 1.82; 95% CI, 1.09-3.04 (p = 0.022), respectively). The evaluated polymorphisms of the AGT and AGTR1 genes did not contribute to the presence of HBP in the present study and may be seen as predisposing factors, while ACE ID genotypes were associated with significantly increased odds for the development of HBP in the Lithuanian child and adolescent population - especially in boys.

  20. Renin-angiotensin system-related highlights from the High Blood Pressure Research Conference annual meeting.

    Science.gov (United States)

    Luft, Friedrich C

    2008-12-01

    The High Blood Pressure Research Conference of the American Heart Association is a theoretical meeting for hypertension researchers who direct their attention to hypertension-related basic disease mechanisms. The items that I have selected for this brief review are molecular intracellular receptor function, novel angiotensin (Ang)-related pathways, including Ang-(1-7), the Mas receptor, and angiotensin-converting enzyme 2, oxidative stress, immunity, the (pro)renin receptor, and until now unappreciated signalling pathways, such as the tonicity element binding protein.

  1. Therapeutic Approaches in Lowering Albuminuria : Travels Along the Renin-Angiotensin-Aldosterone-System Pathway

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo J.

    Achieving optimal blood pressure and albuminuria control is a major therapeutic treatment goal in patients with renal insufficiency. Angiotensin-converting enzyme-inhibitors (ACEIs) and angiotensin-receptor blockers (ARB) are the mainstay of therapy in these patients. However, despite these

  2. Influence of the renin-angiotensin system on human forearm blood flow

    DEFF Research Database (Denmark)

    Stadeager, C; Hesse, B; Henriksen, O

    1990-01-01

    Although angiotensin II is a potent vasoconstrictor agent in all tissues, including the human forearm, equivocal effects on forearm blood flow (FBF) have been found after angiotensin blockade. In 13 healthy Na(+)-depleted subjects FBF was measured by the 133Xe washout technique; subcutaneous...... and muscle blood flows were determined separately. FBF was measured during supine rest, after the arm was lowered, and during lower body negative pressure (LBNP). The measurements were repeated during intra-arterial saralasin infusion in six subjects and after intravenous administration of enalapril in seven....... It is concluded that, in the human forearm, angiotensin II is not necessary for sympathetic vasoconstrictor reflexes but may, through a central effect, have some influence on arteriolar tone at rest....

  3. Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study.

    Science.gov (United States)

    Schmidt, Morten; Mansfield, Kathryn E; Bhaskaran, Krishnan; Nitsch, Dorothea; Sørensen, Henrik Toft; Smeeth, Liam; Tomlinson, Laurie A

    2017-03-09

    Objective  To examine long term cardiorenal outcomes associated with increased concentrations of creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment. Design  Population based cohort study using electronic health records from the Clinical Practice Research Datalink and Hospital Episode Statistics. Setting  UK primary care, 1997-2014. Participants  Patients starting treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers (n=122 363). Main outcome measures  Poisson regression was used to compare rates of end stage renal disease, myocardial infarction, heart failure, and death among patients with creatinine increases of 30% or more after starting treatment against those without such increases, and for each 10% increase in creatinine. Analyses were adjusted for age, sex, calendar period, socioeconomic status, lifestyle factors, chronic kidney disease, diabetes, cardiovascular comorbidities, and use of other antihypertensive drugs and non-steroidal anti-inflammatory drugs. Results  Among the 2078 (1.7%) patients with creatinine increases of 30% or more, a higher proportion were female, were elderly, had cardiorenal comorbidity, and used non-steroidal anti-inflammatory drugs, loop diuretics, or potassium sparing diuretics. Creatinine increases of 30% or more were associated with an increased adjusted incidence rate ratio for all outcomes, compared with increases of less than 30%: 3.43 (95% confidence interval 2.40 to 4.91) for end stage renal disease, 1.46 (1.16 to 1.84) for myocardial infarction, 1.37 (1.14 to 1.65) for heart failure, and 1.84 (1.65 to 2.05) for death. The detailed categorisation of increases in creatinine concentrations (creatinine increases of less than 30% were also associated with increased incidence rate ratios for all outcomes, including death (1.15 (1.09 to 1.22) for increases of 10-19% and 1.35 (1.23 to 1.49) for increases of 20-29%, using creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment were associated with adverse cardiorenal outcomes in a graduated relation, even below the guideline recommended threshold of a 30% increase for stopping treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. Discovery and Characterization of Alamandine, a Novel Component of the Renin-Angiotensin System

    DEFF Research Database (Denmark)

    Lautner, Roberto Q.; Villela, Daniel C; Fraga-Silva, Rodrigo A

    2013-01-01

    by angiotensin-(1-7), including vasodilation, anti-fibrosis, anti-hypertensive and central effects. Interestingly, our data reveals that its actions are independent of the known vasodilator receptors of the RAS, Mas and AT2. Rather, we demonstrate that alamandine acts through the Mas-related G-Protein coupled...

  5. Alteration of the renin-angiotensin system in caerulein induced acute pancreatitis in the mouse.

    Science.gov (United States)

    Gaddam, Ravinder Reddy; Ang, Abel Damien; Badiei, Alireza; Chambers, Stephen T; Bhatia, Madhav

    2015-01-01

    The objective of this study was to determine if RAS bioactive enzymes and peptides are perturbed in acute pancreatitis and associated lung injury. The intervention group of mice were treated with ten hourly intraperitoneal (i.p.) injections of caerulein (50 μg/kg) to induce acute pancreatitis. Animals were euthanized, samples of pancreas, lung and blood were collected, and plasma was prepared and stored for subsequent analysis. ACE and ACE2 activities were determined by spectrofluorometric assay. ACE, ACE2, Ang II and Ang-(1-7) levels were quantified by ELISA. There was a significant decrease in ACE2 enzymatic activity in pancreatic and lung tissues of mice with acute pancreatitis. In contrast, there were no significant changes in measured levels of ACE and ACE2 in the pancreas, and lung or activity of ACE in pancreatic and lung tissue following acute pancreatitis. There were no significant differences in the activities and levels of circulating ACE and ACE2 following acute pancreatitis. The ACE to ACE2 activity ratio was markedly increased in pancreatic and lung tissues of mice with acute pancreatitis. No significant changes were observed in the levels of Ang II except for a decrease in lung tissue. No changes were observed in Ang-(1-7) levels in pancreas, lung and plasma between the groups. The Ang II to Ang-(1-7) ratio was increased in the pancreas but was decreased in the lung following caerulein treatment. These data suggest dysregulation of RAS in acute pancreatitis as evidenced by altered Ang II/Ang-(1-7) levels induced by the imbalance of ACE/ACE2 activity. Copyright © 2015. Published by Elsevier India Pvt Ltd.

  6. Dietary sodium intake modulates renal excretory responses to intrarenal angiotensin (1-7) administration in anesthetized rats.

    Science.gov (United States)

    O'Neill, Julie; Corbett, Alan; Johns, Edward J

    2013-02-01

    Angiotensin II at the kidney regulates renal hemodynamic and excretory function, but the actions of an alternative metabolite, angiotensin (1-7), are less clear. This study investigated how manipulation of dietary sodium intake influenced the renal hemodynamic and excretory responses to intrarenal administration of angiotensin (1-7). Renal interstitial infusion of angiotensin (1-7) in anesthetized rats fed a normal salt intake had minimal effects on glomerular filtration rate but caused dose-related increases in urine flow and absolute and fractional sodium excretions ranging from 150 to 200%. In rats maintained for 2 wk on a low-sodium diet angiotensin (1-7) increased glomerular filtration rate by some 45%, but the diuretic and natriuretic responses were enhanced compared with those in rats on a normal sodium intake. By contrast, renal interstitial infusion of angiotensin (1-7) in rats maintained on a high-sodium intake had no effect on glomerular filtration rate, whereas the diuresis and natriuresis was markedly attenuated compared with those in rats fed either a normal or low-sodium diet. Plasma renin and angiotensin (1-7) were highest in the rats on the low-sodium diet and depressed in the rats on a high-sodium diet. These findings demonstrate that the renal hemodynamic and excretory responses to locally administered angiotensin (1-7) is dependent on the level of sodium intake and indirectly on the degree of activation of the renin-angiotensin system. The exact way in which angiotensin (1-7) exerts its effects may be dependent on the prevailing levels of angiotensin II and its receptor expression.

  7. Anatomical relationship between the collecting system and the intrarenal arteries in the rabbit: contribution for an experimental model.

    Science.gov (United States)

    Shalgum, A; Marques-Sampaio, B P S; Dafalla, A; Pereira-Sampaio, M A

    2012-04-01

    Intrarenal anatomy was studied in detail to evaluate how useful rabbits could be as a urologic model. Only one renal artery was observed, which was divided into dorsal and ventral branches in all cases. Three segmental arteries (cranial, mesorenal and caudal) was the most frequent branching pattern found in both the dorsal and ventral division. There was an important artery related to the ureteropelvic junction in both dorsal and ventral surfaces in all specimens. The cranial pole was supplied by both dorsal and ventral divisions of the renal artery in 23 of 41 casts (56%). Although the cranial pole of the rabbit kidney could be useful as a model because of the resemblances with human kidney, the different relationship between the intrarenal arteries and the kidney collecting system in other regions of the kidney must be taken into consideration by the urologists, when using rabbit kidney in urological research. © 2011 Blackwell Verlag GmbH.

  8. Sonographic detection of intrarenal and intraarterial fungus balls in a preterm infant due to systemic candidiasis

    International Nuclear Information System (INIS)

    Reither, M.; Schumacher, R.; Hagel, K.J.; Hering, F.

    1983-01-01

    Shortly after birth a preterm infant suffering from aspiration syndrome and subsequent Pseudomonas aeruginosa sepsis showed signs of renal insufficiency and mycotic infection: Yeast cells were identified in several urinalyses; there was also an increasing anti-Candida IgM antibody titer. At the same time sonographic examinations revealed an increasing echogenicity of the renal cortex and echogenic masses of variable size which did not cause acoustic shadows in both enlarged kidneys. A few days later, we found a right-sided hydronephrosis caused by an intraureteric prevesical mass of equal echogenicity. As we could observe sonographically, the aggressive antimycotic therapy was successful. Eleven weeks later there were signs of cardiac insufficiency. An angiographically demonstrated filling defect within the pulmonary artery showed the same sonographic findings as the previously found intrarenal masses. The baby underwent embolectomy and recovered. The thrombotic material contained yeast cells giving evidence of systemic Candidasis. Provided appropriate equipment is available, ultrasound today is an excellent non-invasive screening and followup method not only for echoencephalography, but also for more complicated neonatologic problems as seen here. The detailed observation of a changing echogenicity of the renal cortex and pelvis is important and often allows a decisive diagnostic clue before other radiological methods become conclusive. (orig.) [de

  9. Intrarenal Mas and AT1 receptors play a role in mediating the excretory actions of renal interstitial angiotensin-(1-7) infusion in anaesthetized rats.

    Science.gov (United States)

    O'Neill, Julie; Healy, Vincent; Johns, Edward J

    2017-12-01

    What is the central question of this study? Dietary sodium manipulation alters the magnitude of angiotensin-(1-7) [Ang-(1-7)]-induced natriuresis. The present study sought to determine whether this was related to relative changes in the activity of intrarenal Mas and/or AT 1 receptors. What is the main finding and its importance? Angiotensin-(1-7)-induced diuresis and natriuresis is mediated by intrarenal Mas receptors. However, intrarenal AT 1 receptor blockade also had an inhibitory effect on Ang-(1-7)-induced natriuresis and diuresis. Thus, Ang-(1-7)-induced increases in sodium and water excretion are dependent upon functional Mas and AT 1 receptors. We investigated whether angiotensin-(1-7) [Ang-(1-7)]-induced renal haemodynamic and excretory actions were solely dependent upon intrarenal Mas receptor activation or required functional angiotensin II type 1 (AT 1 ) receptors. The renin-angiotensin system was enhanced in anaesthetized rats by prior manipulation of dietary sodium intake. Angiotensin-(1-7) and AT 1 and Mas receptor antagonists were infused into the kidney at the corticomedullary border. Mas receptor expression was measured in the kidney. Mean arterial pressure, urine flow and fractional sodium excretion were 93 ± 4 mmHg, 46.1 ± 15.7 μl min -1  kg -1 and 1.4 ± 0.3%, respectively, in the normal-sodium group and 91 ± 2 mmHg, 19.1 ± 3.3 μl min -1  kg -1 and 0.7 ± 0.2%, respectively, in the low-sodium group. Angiotensin-(1-7) infusion had no effect on mean arterial pressure in rats receiving a normal-sodium diet but decreased it by 4 ± 5% in rats receiving a low-sodium diet (P < 0.05). Interstitial Ang-(1-7) infusion increased urine flow twofold and fractional sodium excretion threefold (P < 0.05) in rats receiving a normal-sodium diet and to a greater extent, approximately three- and fourfold, respectively, in rats receiving the low-sodium diet (both P < 0.05). Angiotensin-(1-7)-induced increases in urine flow and

  10. EFFECT OF THE COMBINED ANTIHYPERTENSIVE THERAPY WITH TARGET BLOOD PRESSURE ACHIEVEMENT ON INTRARENAL BLOOD FLOW IN PATIENTS WITH TYPE 2 DIABETES

    Directory of Open Access Journals (Sweden)

    O. A. Koshel'skaya

    2012-01-01

    Full Text Available Aim. To compare the dynamics of intrarenal vascular resistance (IRVR, circadian blood pressure (BP profile and glomerular filtration rate (GFR in patients with arterial hypertension (HT and type 2 diabetes mellitus (DM who achieved the target BP levels (<130/80 mmHg due to long-term combined antihypertensive therapy with or without renin-angiotensin-aldosterone system (RAAS inhibitors. Material and methods. Patients (n=61 with HT and DM without clinical symptoms of nephroangiopathy were included into the open randomized study , 59 of these patients completed study. Patients of Group 1 (n=41 received therapy with valsartan (n=20, 80–160 mg/day , or perindopril (n=21, 5–10 mg/day , in combination with indapamide retard, 1.5 mg/day , and amlodipine, 5–10 mg/day. Patients of Group 2 (n=18 received amlodipine (5–10 mg/day in combination with indapamide retard (1.5 mg/day and metoprolol succinate (50–100 mg/day. Initially and after 30–32 weeks of therapy the following examinations were performed: duplex ultrasound scanning of the main renal (MRA and intrarenal arteries (IRA with resistive index (RI calculation, ambulatory BP monitoring (ABPM, GFR calculation (by Cockcroft-Gault formula. Results. The target BP levels were achieved in all patients of both groups. Patient’s baseline characteristics including age, sex, duration of disease, office BP , GFR, RI in MRA and IRA did not differ in the groups as well as decrease in office BP due to treatment. However patients of Group 2 had higher levels of systolic BP and systolic BP load at night time than these in patients of Group 1 during all period of the treatment. In patients of Group 2 RI in MRA and arcuate IRA were increased from 0.67±0.06 to 0.69±0.06 (p=0.02 and from 0.62±0.07 to 0.64±0.06 (p=0.02, respectively. The increase in IRA was positively associated with systolic BP at night time in these patients (r=0.6; p=0.01. There were no significant changes of IRA in Group 1 totally

  11. From preeclampsia to renal disease : a role of angiogenic factors and the renin-angiotensin aldosterone system?

    NARCIS (Netherlands)

    van der Graaf, Anne Marijn; Toering, Tsjitske J.; Faas, Marijke M.; Lely, A. Titia

    2012-01-01

    Complicating up to 8% of pregnancies, preeclampsia is the most common glomerular disease worldwide and remains a leading cause of infant and maternal morbidity and mortality. Although the exact pathogenesis of this syndrome of hypertension and proteinuria is still incomplete, a consistent line of

  12. Antidiabetic mechanisms of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists: beyond the renin-angiotensin system

    Czech Academy of Sciences Publication Activity Database

    Kurtz, T. W.; Pravenec, Michal

    2004-01-01

    Roč. 22, č. 12 (2004), s. 2253-2261 ISSN 0263-6352 R&D Projects: GA ČR GA301/03/0751 Grant - others:HHMI(US) HHMI55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : angiotensin II receptors * metabolic syndrome * peroxisome proliferator activated receptors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.871, year: 2004

  13. Progression of Renal Insufficiency in Patients with Essential Hypertension Treated with Renin Angiotensin Aldosterone System Blockers: An Electrocardiographic Correlation

    Directory of Open Access Journals (Sweden)

    Luis Rodriguez-Padial

    2017-12-01

    Full Text Available Background: There is a frequent association between renal insufficiency and cardiovascular disease in patients with essential hypertension (HTN. The aim of this study was to analyze the relationship between ECG parameters and the progress of renal damage in patients with treated HTN. Methods: 109 patients with HTN had their microalbuminuria monitored over a 3-year time frame. During the last 3 months of follow-up, an ECG was recorded. Patients were divided into 3 groups according to the deterioration of their renal function: normoalbuminuria during the study period (normo–normo; n = 51; normoalbuminuria developing microalbuminuria (normo–micro; n = 29; and microalbuminuria at baseline (micro–micro; n = 29. Results: There were no differences in presence of left ventricular hypertrophy between the 3 groups. RV6/RV5 >1 was observed more frequently as renal function declined (p = 0.025. The 12-lead QRS-complex voltage-duration product was significantly increased in patients without microalbuminuria at baseline who went on to develop microalbuminuria (p = 0.006. Patients who developed microalbuminuria during follow-up, with positive Cornell voltage criteria, showed a lesser degree of progression of microalbuminuria when compared with the rest of the subgroups (p = 0.044. Furthermore, patients with microalbuminuria at baseline treated with angiotensin receptor blockers and diuretics, and positive Cornell voltage criteria, showed a higher degree of microalbuminuria compared to those with negative Cornell voltage criteria (p = 0.016. Conclusions: In patients with HTN, we identified some ECG parameters, which predict renal disease progression in patients with HTN, which may permit the identification of patients who are at risk of renal disease progression, despite optimal antihypertensive pharmacotherapy.

  14. Severe hypoglycaemia in type 1 diabetes: impact of the renin-angiotensin system and other risk factors

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik

    2009-01-01

    this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could contribute to improved prediction of, and inspire...... and the need for assistance from other persons in order to manage the situation. Such episodes represent the most feared side effect to insulin treatment and are regarded as the major limiting factor for achievement of recommended glycaemic targets in type 1 diabetes. The series of studies that constitute...... to novel preventive measures of, severe hypoglycaemia. Our studies confirm that severe hypoglycaemia is still a major clinical problem in type 1 diabetes. The individual susceptibility to severe hypoglycaemia is highly varying and conventional risk factors - with major contribution from hypoglycaemia...

  15. Severe hypoglycaemia in type 1 diabetes: impact of the renin-angiotensin system and other risk factors

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik

    2009-01-01

    this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could contribute to improved prediction of, and inspire...... diabetes. The series of studies that constitute this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could...... and the need for assistance from other persons in order to manage the situation. Such episodes represent the most feared side effect to insulin treatment and are regarded as the major limiting factor for achievement of recommended glycaemic targets in type 1 diabetes. The series of studies that constitute...

  16. Benefits of early intervention in the progression of cardiovascular disease - role of renin-angiotensin system blockade

    International Nuclear Information System (INIS)

    Jaffary, M.H.

    2002-01-01

    Atherosclerosis is a slowly progressive process. It begins early, progresses insidiously for many years, remains asymptotic and by the time it manifests as coronary artery disease or stroke, the atherosclerotic burden is immense. The question in that why does it remain asymptotic for so long? The answer lies in the fact that blood vessels are able to accommodate huge amount of plaque before the lumen becomes compromised. It is only when the plaque burden becomes severe that the lumen of the vessels becomes clogged and the symptoms start appearing. In fact the atherosclerotic process begins after the first decade of life. More so in the recent years when the fast food culture has prevailed along with significant changes in life style with decreased physical activity and increasing trend towards obesity. The process progresses steadily over the third and fourth decade of life and beyond. The fatty streaks grow to form fibrous plaques which may narrow or occlude the arterial lumen. Complex lesions may become unstable and rupture, leading to acute coronary events such as unstable angina, myocardial infarction and stroke. (author)

  17. Determinants of the renin-angiotensin-aldosterone system in cirrhosis with special emphasis on the central blood volume

    DEFF Research Database (Denmark)

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

    2006-01-01

    of the RAAS and its potential determinants with special focus on the central and arterial blood volume (CBV). MATERIAL AND METHODS: Eighty-nine patients (Child class A/B/C: 19/41/29) and 32 controls were included in the study. All were given a haemodynamic examination with measurement of determinants...

  18. Is the use of renin-angiotensin system inhibitors in patients with aortic valve stenosis safe and of prognostic benefit?

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Abdulla, Jawdat

    2017-01-01

    risk [576/3389 patients receiving RASi vs. 1118/4384 controls died; relative risk 0.93 (95% confidence interval 0.78-1.11), P = 0.44]. Use of RASi was also observed to lower the risk of aortic valve replacement (AVR) surgery [67/2913 patients with RASi vs. 154/3666 controls underwent AVR; relative risk......Aortic valve stenosis (AVS) is associated with significant morbidity and mortality, especially in the presence of symptoms and echocardiographic signs of left ventricular remodelling (i.e. increase in left ventricular mass, left ventricular dilation, and systolic dysfunction). Renin...... for inclusion (PubMed, EMBASE, and Cochrane library search criteria: aortic stenosis, aortic valve, angiotensin-converting enzyme inhibitor in different combinations, published in English at any time up to 1 April 2016). Our analyses suggested that use of RASi was safe, with no observed increase in mortality...

  19. NT-pro-BNP during hypoglycemia and hypoxemia in normal subjects: impact of renin-angiotensin system activity

    DEFF Research Database (Denmark)

    Due-Andersen, R; Pedersen-Bjergaard, U; Høi-Hansen, T

    2008-01-01

    (mean nadir Po-2 5.8 +/- 0.5 kPa), and 3) normoglycemic normoxia (control). NT-pro-BNP was measured at baseline, during the stimuli, and in the recovery phase. Hypoxemia was associated with a 9% increase in NT-pro-BNP from 2.2 +/- 1.5 pmol/l at baseline to 2.4 +/- 1.5 pmol/l during hypoxemia (P

  20. Severe hypoglycaemia in type 1 diabetes: impact of the renin-angiotensin system and other risk factors

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik

    2009-01-01

    Hypoglycaemia is an unavoidable side effect to insulin therapy of diabetes. In daily life some hypoglycaemic episodes are recognised by the patients and corrected by ingestion of glucose, but occasionally unrecognised episodes progress into severe hypoglycaemia with cognitive impairment and the n......Hypoglycaemia is an unavoidable side effect to insulin therapy of diabetes. In daily life some hypoglycaemic episodes are recognised by the patients and corrected by ingestion of glucose, but occasionally unrecognised episodes progress into severe hypoglycaemia with cognitive impairment...... and the need for assistance from other persons in order to manage the situation. Such episodes represent the most feared side effect to insulin treatment and are regarded as the major limiting factor for achievement of recommended glycaemic targets in type 1 diabetes. The series of studies that constitute...

  1. Effects of enalapril maleate on blood pressure, renin-angiotensin-aldosterone system, and peripheral sympathetic activity in essential hypertension.

    Science.gov (United States)

    Cerasola, G; Cottone, S; D'Ignoto, G; Grasso, L; Carone, M B; Carapelle, E; Contorno, A

    1987-01-01

    Recent experimental studies showed that inhibition of angiotensin II synthesis may reduce sympathetic activity as evaluated by plasma catecholamine assay, sharing in the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors. Fifteen patients with essential hypertension were studied. Blood pressure and heart rate were evaluated both at rest and after stressor laboratory tests, before and four hours after administration of 20 mg of enalapril maleate and on the 14th and 120th days of continued administration. At the same time, blood samples were drawn for determinations of plasma renin activity, ACE, angiotensin II, plasma aldosterone concentration, and plasma norepinephrine levels. Enalapril in a dosage of 20 mg/day significantly and progressively lowered systolic and diastolic blood pressure at rest, with maximal decreases observed on the 120th day of the study period (P less than 0.001). Heart rate at rest and after exercise showed no significant differences throughout the study period. Good blood pressure control was observed during stressor laboratory tests. The greatest impact of blood pressure was observed on the 120th day during dynamic exercise (mean blood pressure from 139 +/- 3.9 to 111.5 +/- 6.3 mmHg; P less than 0.01) and on the 14th day during the cold pressure test (mean blood pressure from 133.3 +/- 3.9 to 111.2 +/- 4.7 mmHg; P less than 0.005). A marked and persistent ACE inhibition and a gradual and progressive decrease of angiotensin II (from 12.42 +/- 2.15 to 5.45 +/- 1.68 pg/ml; P less than 0.005) characterized the humoral activity of enalapril maleate. Moreover, a significant decrease of plasma norepinephrine levels was observed during the follow-up period with maximal reduction on the 120th day (from 311 +/- 34 to 197 +/- 33 pg/ml; P less than 0.01). It has been demonstrated that the pressor effect of angiotensin II was blunted during exercise. Our hemodynamic and humoral results appear to confirm the hypothesis that enalapril maleate may reduce blood pressure by direct inhibition of ACE and of kininase II as well as by a decreased sympathetic output, which may be secondary to angiotensin II inhibition. These results agree with the recent experimental demonstration of a reduced sympathetic nervous response to nerve stimulation during ACE inhibition.

  2. New perspectives in the renin-angiotensin-aldosterone system (RAAS) II: albumin suppresses angiotensin converting enzyme (ACE) activity in human.

    Science.gov (United States)

    Fagyas, Miklós; Úri, Katalin; Siket, Ivetta M; Fülöp, Gábor Á; Csató, Viktória; Daragó, Andrea; Boczán, Judit; Bányai, Emese; Szentkirályi, István Elek; Maros, Tamás Miklós; Szerafin, Tamás; Édes, István; Papp, Zoltán; Tóth, Attila

    2014-01-01

    About 8% of the adult population is taking angiotensin-converting enzyme (ACE) inhibitors to treat cardiovascular disease including hypertension, myocardial infarction and heart failure. These drugs decrease mortality by up to one-fifth in these patients. We and others have reported previously that endogenous inhibitory substances suppress serum ACE activity, in vivo, similarly to the ACE inhibitor drugs. Here we have made an effort to identify this endogenous ACE inhibitor substance. ACE was crosslinked with interacting proteins in human sera. The crosslinked products were immunoprecipitated and subjected to Western blot. One of the crosslinked products was recognized by both anti-ACE and anti-HSA (human serum albumin) antibodies. Direct ACE-HSA interaction was confirmed by binding assays using purified ACE and HSA. HSA inhibited human purified (circulating) and human recombinant ACE with potencies (IC50) of 5.7 ± 0.7 and 9.5 ± 1.1 mg/mL, respectively. Effects of HSA on the tissue bound native ACE were tested on human saphenous vein samples. Angiotensin I evoked vasoconstriction was inhibited by HSA in this vascular tissue (maximal force with HSA: 6.14 ± 1.34 mN, without HSA: 13.54 ± 2.63 mN), while HSA was without effects on angiotensin II mediated constrictions (maximal force with HSA: 18.73 ± 2.17 mN, without HSA: 19.22 ± 3.50 mN). The main finding of this study is that HSA was identified as a potent physiological inhibitor of the ACE. The enzymatic activity of ACE appears to be almost completely suppressed by HSA when it is present in its physiological concentration. These data suggest that angiotensin I conversion is limited by low physiological ACE activities, in vivo.

  3. New perspectives in the renin-angiotensin-aldosterone system (RAAS I: endogenous angiotensin converting enzyme (ACE inhibition.

    Directory of Open Access Journals (Sweden)

    Miklós Fagyas

    Full Text Available Angiotensin-converting enzyme (ACE inhibitors represent the fifth most often prescribed drugs. ACE inhibitors decrease 5-year mortality by approximately one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors, which endogenous inhibitory effects are much less characterized than that for the clinically administered ACE inhibitors. Here we aimed to investigate this endogenous ACE inhibition in human sera. It was hypothesized that ACE activity is masked by an endogenous inhibitor, which dissociates from the ACE when its concentration decreases upon dilution. ACE activity was measured by FAPGG hydrolysis first. The specific (dilution corrected enzyme activities significantly increased by dilution of human serum samples (23.2 ± 0.7 U/L at 4-fold dilution, 51.4 ± 0.3 U/L at 32-fold dilution, n = 3, p = 0.001, suggesting the presence of an endogenous inhibitor. In accordance, specific enzyme activities did not changed by dilution when purified renal ACE was used, where no endogenous inhibitor was present (655 ± 145 U/L, 605 ± 42 U/L, n = 3, p = 0.715, respectively. FAPGG conversion strongly correlated with angiotensin I conversion suggesting that this feature is not related to the artificial substrate. Serum samples were ultra-filtered to separate ACE (MW: 180 kDa and the hypothesized inhibitor. Filtering through 50 kDa filters was without effect, while filtering through 100 kDa filters eliminated the inhibiting factor (ACE activity after <100 kDa filtering: 56.4 ± 2.4 U/L, n = 4, control: 26.4 ± 0.7 U/L, n = 4, p<0.001. Lineweaver-Burk plot indicated non-competitive inhibition of ACE by this endogenous factor. The endogenous inhibitor had higher potency on the C-terminal active site than N-terminal active site of ACE. Finally, this endogenous ACE inhibition was also present in mouse, donkey, goat, bovine sera besides men (increasing of specific ACE activity from 4-fold to 32-fold dilution: 2.8-fold, 1.7-fold, 1.5-fold, 1.8-fold, 2.6-fold, respectively. We report here the existence of an evolutionary conserved mechanism suppressing circulating ACE activity, in vivo, similarly to ACE inhibitory drugs.

  4. Responses to dehydration in the one-humped camel and effects of blocking the renin-angiotensin system.

    Directory of Open Access Journals (Sweden)

    Mahmoud Alhaj Ali

    Full Text Available Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP.

  5. 胎児・新生児における電解質平衡とrenin-angiotensin-aldosterone動態に関する研究

    OpenAIRE

    山口, 進久; Nobuhisa, YAMAGUCHI; 日本大学医学部産科学婦人科学教室; Department of Obstetrics and Gynecology, Nihon University School of Medidne

    1981-01-01

    胎児・新生児におけるrenin-angiotensin-aldosterone(R-A-ALDO)系と体液・電解質平衡との関連を知るため, 児娩出時より目齢第8日迄の血中動態を検討し, 以下の成績を得た.1.生下時体重が3.0kg以上の群で児娩出時のそれぞれの濃度を比較すると, ALDO, deoxycorticosterone(DOC)ならびにA-II, plasma renin activity(PRA)濃度は〓帯血, 18-hydroxycorticosterone(180H-B)およびACTH濃度は母体末梢血で高値となつた.一方, K^+値は膀帯血で高くNa^+, Cl^-値には母児間で相違がなかつた.2.〓帯動脈血のALDO濃度には18 0H-BあるいはACTH濃度と一定の相関性があり, DOCあるいはA-II, Na^+, K^+濃度の間に相関性を認めなかつた.膀帯動・静脈血間ではALDO, 18 OH-BおよびPRA間に, また動脈血のALDOと静脈血のDOC, 18 OH-B濃度間にそれぞれ相関性があり, A-IIとの間にそれを認めなかつた.3.生下時体重が2.5...

  6. Sonographic detection of intrarenal and intra-arterial fungus balls in a preterm infant due to systemic candidiasis

    Energy Technology Data Exchange (ETDEWEB)

    Reither, M.; Schumacher, R.; Hagel, K.J.; Hering, F.

    1983-10-01

    Shortly after birth a preterm infant suffering from aspiration syndrome and subsequent Pseudomonas aeruginosa sepsis showed signs of renal insufficiency and mycotic infection: yeast cells were identified in several urinalyses; there was also an increasing anti-candida IgM antibody titer. At the same time sonographic examinations revealed an increasing echogenicity of the renal cortex and echogenic masses of variable size which did not cause acoustic shadows in both enlarged kidneys. A few days later, we found a right-sided hydronephrosis caused by an intraureteric prevesical mass of equal echogenicity. As we could observe sonographically, the aggressive antimycotic therapy was successful. Eleven weeks later there were signs of cardiac insufficiency. An angiographically demonstrated filling defect, within the pulmonary artery, showed the same sonographic findings as the previously found intrarenal masses. The baby underwent embolectomy and recovered. The thrombotic material contained yeast cells giving evidence of systemic candidasis. Provided appropriate equipment is available, ultrasound today is an excellent non-invasive screening and followup method not only for echoencephalography, but also for more complicated neonatologic problems as seen here. The detailed observation of a changing echogenicity of the renal cortex and pelvis is important and often allows a decisive diagnostic clue before other radiological methods become conclusive.

  7. Study of the components of renin-angiotensinaldosterone system and KalliKrein -Kinin system in normal pregnancy

    International Nuclear Information System (INIS)

    Abreu Fagundes, V.G. de.

    1984-01-01

    The alterations in the renin-angiotensin-aldosterone system and Kallikrein-Kinin system were studied. The possible interferences of these systems on the arterial pressure and on the evolution of normal pregnancy were presented in the following situations: when the pregnant change from dorsal decumbency to left lateral decumbency and to orthostatic position. (M.A.C.) [pt

  8. Reduced baroreflex sensitivity in alcoholic cirrhosis: relations to hemodynamics and humoral systems

    DEFF Research Database (Denmark)

    Møller, Søren; Iversen, Jens S; Henriksen, Jens H

    2007-01-01

    In cirrhosis, arterial vasodilatation leads to central hypovolemia and activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. As the liver disease and circulatory dysfunction may affect baroreflex sensitivity (BRS), we assessed BRS in a large group of patients with cirrh...

  9. Cardiovascular and neuroendocrine responses to water immersion in compensated heart failure

    DEFF Research Database (Denmark)

    Gabrielsen, Anders; Sørensen B., Vibeke; Pump, Bettina

    2000-01-01

    sympathetic nervous activity, arginine vasopressin, renin-angiotensin system, endothelin, baroreceptors......sympathetic nervous activity, arginine vasopressin, renin-angiotensin system, endothelin, baroreceptors...

  10. Renin–angiotensin system inhibition is not associated with increased sudden cardiac death, cardiovascular mortality or all-cause mortality in patients with aortic stenosis

    DEFF Research Database (Denmark)

    Bang, Casper N; Greve, Anders M; Køber, Lars

    2014-01-01

    BACKGROUND: Renin-angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild...

  11. Intrarenal neuroblastoma mimics Wilms' tumor

    International Nuclear Information System (INIS)

    Muniz, Maria T. Cartaxo; Soares, Andrezza B.; Freitas, Elizabete M.; Araujo, Marcela; Pureza, Leda M.M.; Morais, Adriana; Antunes, Consuelo; Salles, Terezinha de J. Marques; Borges, Josenilda C.; Morais, Vera L.L. de; Romualdo Filho, Jose; Magalhaes, Mario H.

    2005-01-01

    This work reports the case history of a child with intrarenal neuroblastoma, initially diagnosed as Wilms' tumor. The patient, a one year and three months old girl, presented a hard abdominal mass on the left flank that extended to the meso gastric region, plus fever and paleness. The ultrasound of the entire abdomen revealed an intrarenal mass. Biopsy with fine needle in many points of the tumor revealed Wilms' tumor. The scarcely of the material, however, made immunohistoquemistry impossible at that moment. Because of the child's severe condition the SIOP protocol was started. As no clinical response was observed, an exploratory laparotomy was indicated with partial resection of the tumor and bone marrow aspiration (MO). The histopathologic study revealed a malignant neoplasia of small cells, poorly differentiated. IHQ was negative for WT-1 and positive for NB-84, synaptofisin, cromogranine. N-myc amplification was observed by molecular biology. The bone marrow aspiration identified metastatic small round cells infiltration. Intrarenal neuroblastoma is a rare entity that clinically and radiographically resembles Wilms' tumor. The objective of this case report is to show the importance of immunohistochemical and molecular analysis in the diagnosis of intrarenal neuroblastoma. (author)

  12. Changes in the renin-angiotensin-aldosterone system in response to dietary salt intake in normal and hypertensive pregnancy. A randomized trial

    DEFF Research Database (Denmark)

    Nielsen, Lise H; Ovesen, Per; Hansen, Mie R

    2016-01-01

    during low-salt diet in PE patients (n = 7), healthy pregnant women (n = 15), and nonpregnant women (n = 13). High-salt intake decreased renin and angiotensin II concentrations significantly in healthy pregnant women (P ... in aldosterone and increases in brain natriuretic peptid (BNP) were similar in the groups. In PE patients, uterine and umbilical artery indices were not adversely changed during low-salt diet. Creatinine clearance was significantly lower in PE with no change by salt intake. PE patients displayed alterations...... of plasma renin and angiotensin II in response to changes in dietary salt intake compatible with a primary increase in renal sodium reabsorption in hypertensive pregnancies....

  13. Human in vivo study of the renin-angiotensin-aldosterone system and the sympathetic activity after 8 weeks daily intake of fermented milk

    DEFF Research Database (Denmark)

    Usinger, Lotte; Ibsen, Hans; Linneberg, Allan

    2010-01-01

    Milk fermented by lactic acid bacteria is suggested to have antihypertensive effect in humans. In vitro and animal studies have established an angiotensin-converting enzyme (ACE) inhibitor effect of peptides in fermented milk. However, other modes of action must be considered, because until today...... no human studies have confirmed an ACE inhibition in relation to the intake of fermented milk....

  14. Addition of silymarin to renin-angiotensin system blockers in normotensive patients with type 2 diabetes mellitus and proteinuria: a prospective randomized trial.

    Science.gov (United States)

    Voroneanu, Luminita; Siriopol, Dimitrie; Dumea, Raluca; Badarau, Silvia; Kanbay, Mehmet; Afsar, Baris; Gavrilovici, Cristina; Covic, Adrian

    2017-12-01

    In the last decade, despite constant investigation, no current single treatment has been able to decrease the incidence of diabetic nephropathy and to significantly reduce progression of diabetic CKD. Patients with type 2 diabetes mellitus and proteinuria (>0.5 g/day) after a screening and treatment optimization phase were randomly assigned to receive silymarin or placebo. The primary outcome was a composite outcome: mortality, decline of eGFR > 50% and renal replacement therapy. Secondary outcomes were a composite renal outcome (defined as a decline of eGFR ≥ 50% or ESRD) and also to test the effect of silymarin on the change in eGFR and proteinuria. We also assessed the adverse effects (hospitalizations, headache or gastrointestinal symptoms) during the study. One hundred and two patients were included in the study. There were no significant differences between the two study groups regarding the primary and renal outcomes (HR 0.62, 95% CI 0.3-1.2, p = 0.15; HR 0.56, 95% CI 0.26-1.24, p = 0.16, respectively). At study end, eGFR declined significantly in both arms (p < 0.001), irrespective of the treatment group allocation, and there were no significant changes in proteinuria. There was a significant difference in hospitalizations rates between the two study groups (0.61, 95% CI 0.44-0.85). Silymarin did not show a significant reduction in the primary and secondary outcomes. Importantly, silymarin treatment was associated with a significant reduction in the hospitalization rate.

  15. Long-term use of drugs affecting the renin-angiotensin system and the risk of cancer. A population-based case-control study

    DEFF Research Database (Denmark)

    Hallas, Jesper; Depont Christensen, Rene; Andersen, Morten

    2012-01-01

    Aims: A recent meta-analysis of clinical trials has demonstrated a small excess of cancers in persons that had been allocated to angiotensin-receptor blockers (ARBs). We undertook this observational study to look at dose-response and dose-duration effects and look for specificity with respect...... for each case by a risk-set sampling. Data on medication was retrieved from the Danish National Prescription Registry. We defined long-term exposure as at least 1000 defined daily doses redeemed within the past five years. Confounders were controlled by conditional logistic regression. Results: The odds...

  16. The PGE(2)-EP4 receptor is necessary for stimulation of the renin-angiotensin-aldosterone system in response to low dietary salt intake in vivo

    DEFF Research Database (Denmark)

    Pöschke, Antje; Kern, Niklas; Maruyama, Takayuki

    2012-01-01

    a similar attenuation of Na(+) excretion; however, diuresis and K(+) excretion were enhanced, and plasma Na(+) concentration was higher, whereas plasma K(+) concentration was lower compared with control diet. There were no significant differences between EP4(+/+) and EP4(-/-) mice in blood pressure......Increased cyclooxygenase-2 (COX-2) expression and PGE(2) synthesis have been shown to be prerequisites for renal renin release after Na(+) deprivation. To answer the question of whether EP4 receptor type of PGE(2) mediates renin regulation under a low-salt diet, we examined renin regulation in EP4......(+/+), EP4(-/-), and in wild-type mice treated with EP4 receptor antagonist. After 2 wk of a low-salt diet (0.02% wt/wt NaCl), EP4(+/+) mice showed diminished Na(+) excretion, unchanged K(+) excretion, and reduced Ca(2+) excretion. Diuresis and plasma electrolytes remained unchanged. EP4(-/-) exhibited...

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

    Science.gov (United States)

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

    2009-01-01

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

  18. Predictors of Long-Term Mortality and Frequent Re-Hospitalization in Patients with Acute Decompensated Heart Failure and Kidney Dysfunction Treated with Renin-Angiotensin System Blockers.

    Science.gov (United States)

    Baydemir, Canan; Ural, Dilek; Karaüzüm, Kurtuluş; Balci, Sibel; Argan, Onur; Karaüzüm, Irem; Kozdağ, Güliz; Ağır, Ayşen A

    2017-07-10

    BACKGROUND Assessment of risk for all-cause mortality and re-hospitalization is an important task during discharge of acute heart failure (AHF) patients, as they warrant different management strategies. Treatment with optimal medical therapy may change predictors for these 2 end-points in AHF patients with renal dysfunction. The aim of this study was to evaluate the predictors for long-term outcome in AHF patients with kidney dysfunction who were discharged on optimal medical therapy. MATERIAL AND METHODS The study was conducted retrospectively. The study group consisted of 225 AHF patients with moderate-to-severe kidney dysfunction, who were hospitalized at Kocaeli University Hospital Cardiology Clinic and who were prescribed beta-blockers and ACE-inhibitors or angiotensin II receptor blockers at discharge. Clinical, echocardiographic, and biochemical predictors of the composite of total mortality and frequent re-hospitalization (≥3 hospitalizations during the follow-up) were assessed using Cox regression and the predictors for each end-point were assessed by competing risk regression analysis. RESULTS Incidence of all-cause mortality was 45.3% and frequent readmissions were 49.8% in a median follow-up of 54 months. The associates of the composite end-point were age, NYHA class, respiration rate on admission, eGFR, hypoalbuminemia, mitral valve E/E' ratio, and ejection fraction. In competing risk regression analysis, right-sided HF, hypoalbuminemia, age, and uric acid appeared as independent associates of all-cause mortality, whereas NYHA class, NT-proBNP, mitral valve E/E' ratio, and uric acid were predictors for re-hospitalization. CONCLUSIONS Predictors for all-cause mortality in AHF with kidney dysfunction treated with optimal therapy are mainly related to advanced HF with right-sided dysfunction, whereas frequent re-hospitalization is associated with volume overload manifested by increased mitral E/E' ratio and NT-proBNP levels.

  19. The efficacy and safety of dual blockage of the renin-angiotensin-aldosterone system in patients with type 2 diabetes, hypertension and obesity without renal dysfunction

    Directory of Open Access Journals (Sweden)

    S A Savelyeva

    2012-09-01

    Full Text Available The purpose of the study was to evaluate the clinical efficacy and safety of dual RAAS blockage during treatment with angiotensin-converting enzyme (ACE inhibitors in combination with a direct renin inhibitor (PIR aliskiren versus combination therapy with ACE inhibitors and angiotensin receptor blocker II (ARB valsartan in patients with type 2 diabetes mellitus (T2DM, arterial hypertension (AH and obesity, without renal dysfunction. Materials and methods. The study included 26 patients with T2DM (10 men and 16 women, mean age 59,0±6,2 years with inadequate control of blood pressure (over 130 and/or 80 mm Hg on prior antihypertensive therapy and without renal dysfunctions (glomerular filtration rate (GFR> 60 ml/min/1, 73 m2 and the of albumin/creatinine (A/C ratio in the morning urine sample <10 mg/mol. After screening with the continuation of the initial therapy, including ACE inhibitors, 14 patients were added aliskiren 150–300 mg/day, 12 patients – valsartan 80–160 mg/day. Evaluation of the treatment effectiveness in terms of blood pressure (mean of three consecutive measurements in the sitting position and the parameters of renal function (serum creatinine and potassium, GFR, A/C ratio in the urine was performed at 4, 12 and 24 weeks of therapy. Results. In the group of patients treated with aliskiren, after 4 weeks of treatment a significant decrease in systolic and diastolic blood pressure (SBP and DBP, respectively was noted as compared to baseline: 146,1 and 138,9 mm Hg, p<0,05, 87,1 and 81,1 mm Hg, p <0,05, respectively; with systolic BP after 24 weeks of treatment decreased to 127,8 (-18,2 mm Hg, p<0,05, diastolic BP to 75,0 (-12, 1 mm Hg, p<0,05, the target blood pressure (≤130/80 mm Hg was achieved in 83% of patients. The group of patients treated with valsartan, after 4 weeks of therapy showed a significant reduction in systolic BP 148 and 141,6 mm Hg, p <0,05, diastolic BP - to 85,8 and 81,7 mm Hg, p=0,059; after 24 weeks systolic BP decreased to 128,7 (-19,3 mm Hg, p=0,05, diastolic BP – to 77,5 (-8,3 mm Hg, p=0,07, the target blood pressure was achieved in 78% of patients. When monitoring the safety of therapy in terms of potassium, serum creatinine, GFR, and A/C urine ratio statistically significant differences between the groups at 4, 12, 24 weeks of treatment were observed. Conclusion. Results of the study demonstrate the efficacy and safety of dual RAAS blockage in patients with T2DM and obesity with no prior renal impairment.

  20. Renin-angiotensin system transgenic mouse model recapitulates pathophysiology similar to human preeclampsia with renal injury that may be mediated through VEGF.

    Science.gov (United States)

    Denney, J Morgan; Bird, Cynthia; Gendron-Fitzpatrick, Annette; Sampene, Emmanuel; Bird, Ian M; Shah, Dinesh M

    2017-03-01

    Using a transgenic cross, we evaluated features of preeclampsia, renal injury and the sFlt1/VEGF changes. Transgenic hAGT and hREN, or wild-type (WT) C57Bl/6 mice were cross-bred: female hAGT × male hREN for preeclampsia (PRE) model and female WT × male WT for pregnant controls (WTP). Samples were collected for plasma VEGF, sFlt1, and urine albumin. Blood pressures (BP) were monitored by telemetry. Vascular reactivity was investigated by wire myography. Kidneys and placenta were immunostained for sFlt1 and VEGF. Eleven PRE and 9 WTP mice were compared. PRE more frequently demonstrated albuminuria, glomerular endotheliosis (80% vs. 11%; P = 0.02), and placental necrosis (60% vs. 0%; P preeclampsia recapitulates human preeclamptic state with high fidelity, and that, vascular adaptation to pregnancy is suggested by declining BPs and reduced vascular response to PE and increased response to acetylcholine. Placental damage with resultant increased release of sFlt1, proteinuria, deficient spiral artery remodeling, and glomerular endotheliosis were observed in this model of PRE. Increased VEGF binding to glomerular endothelial cells in this model of PRE is similar to human PRE and leads us to hypothesize that renal injury in preeclampsia may be mediated through local VEGF. Copyright © 2017 the American Physiological Society.

  1. Sex-dependent effects of antenatal glucocorticoids on insulin sensitivity in adult sheep: role of the adipose tissue renin angiotensin system.

    Science.gov (United States)

    Massmann, G Angela; Zhang, Jie; Seong, Won Joon; Kim, Minhyoung; Figueroa, Jorge P

    2017-06-01

    Exposure to glucocorticoids in utero is associated with changes in organ function and structure in the adult. The aims of this study were to characterize the effects of antenatal exposure to glucocorticoids on glucose handling and the role of adipose tissue. Pregnant sheep received betamethasone (Beta, 0.17 mg/kg) or vehicle 24 h apart at 80 days of gestation and allowed to deliver at term. At 9 mo, male and female offspring were fed at either 100% of nutritional allowance (lean) or ad libitum for 3 mo (obese). At 1 yr, they were chronically instrumented under general anesthesia. Glucose tolerance was evaluated using a bolus of glucose (0.25 g/kg). Adipose tissue was harvested after death to determine mRNA expression levels of angiotensinogen (AGT), angiotensin-converting enzyme (ACE) 1, ACE2, and peroxisome proliferator-activated receptor γ (PPAR-γ). Data are expressed as means ± SE and analyzed by ANOVA. Sex, obesity, and Beta exposure had significant effects on glucose tolerance and mRNA expression. Beta impaired glucose tolerance in lean females but not males. Superimposed obesity worsened the impairment in females and unmasked the defect in males. Beta increased ACE1 mRNA in females and males and AGT in females only ( P glucocorticoids. Copyright © 2017 the American Physiological Society.

  2. Enalapril maleate and a lysine analogue (MK-521) in normal volunteers; relationship between plasma drug levels and the renin angiotensin system.

    Science.gov (United States)

    Biollaz, J; Schelling, J L; Jacot Des Combes, B; Brunner, D B; Desponds, G; Brunner, H R; Ulm, E H; Hichens, M; Gomez, H J

    1982-09-01

    1 Two single doses of 10 mg each of the converting enzyme inhibitor enalapril maleate or MK-421 and of its lysine analogue (MK-521) were administered p.o. to twelve male volunteers. 2 The active diacid metabolite of MK-421 and the lysine analogue were determined by radioimmunoassay and MK-421 by the active metabolite method following in vitro hydrolysis. 3 Peak serum levels of MK-421, active metabolite and lysine analogue were reached within 1, 3 to 4, and 6 h respectively. Practically all MK-421 had disappeared from serum within 4 h. 4 A close correlation between percent inhibition of plasma converting enzyme activity and the serum concentration of active metabolite was observed ( r = 0.98, n = 171, P less than 0.001). Similarly, converting enzyme blockade as expressed by the ratio plasma angiotensin II/angiotensin I was closely correlated with serum active metabolite levels (r = 0.93, n = 15, P less than 0.001).

  3. New perspectives in the renin-angiotensin-aldosterone system (RAAS III: endogenous inhibition of angiotensin converting enzyme (ACE provides protection against cardiovascular diseases.

    Directory of Open Access Journals (Sweden)

    Miklós Fagyas

    Full Text Available ACE inhibitor drugs decrease mortality by up to one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors. Here we investigated the clinical significance of this potential endogenous ACE inhibition. ACE concentration and activity was measured in patient's serum samples (n = 151. ACE concentration was found to be in a wide range (47-288 ng/mL. ACE activity decreased with the increasing concentration of the serum albumin (HSA: ACE activity was 56 ± 1 U/L in the presence of 2.4 ± 0.3 mg/mL HSA, compared to 39 ± 1 U/L in the presence of 12 ± 1 mg/mL HSA (values are mean ± SEM. Effects of the differences in ACE concentration were suppressed in human sera: patients with ACE DD genotype exhibited a 64% higher serum ACE concentration (range, 74-288 ng/mL, median, 155.2 ng/mL, n = 52 compared to patients with II genotype (range, 47-194 ng/mL, median, 94.5 ng/mL, n = 28 while the difference in ACE activities was only 32% (range, 27.3-59.8 U/L, median, 43.11 U/L, and range 15.6-55.4 U/L, median, 32.74 U/L, respectively in the presence of 12 ± 1 mg/mL HSA. No correlations were found between serum ACE concentration (or genotype and cardiovascular diseases, in accordance with the proposed suppressed physiological ACE activities by HSA (concentration in the sera of these patients: 48.5 ± 0.5 mg/mL or other endogenous inhibitors. Main implications are that (1 physiological ACE activity can be stabilized at a low level by endogenous ACE inhibitors, such as HSA; (2 angiotensin II elimination may have a significant role in angiotensin II related pathologies.

  4. Polymorphisms of renin-angiotensin system and natriuretic peptide receptor A genes in patients of Greek origin with a history of myocardial infarction.

    Science.gov (United States)

    Karayannis, George; Tsezou, Aspasia; Giannatou, Eirini; Papanikolaou, Vassilios; Giamouzis, Gregory; Triposkiadis, Filippos

    2010-11-01

    We assessed the association between (CA)n repeat polymorphism of angiotensinogen (AGT), 250 base pair (bp) insertion/deletion (I/D) of angiotensin-converting enzyme (ACE), tetranucleotide repeat polymorphism (TCTG)n of renin (REN), (CT)n repeat polymorphism of the natriuretic peptide receptor A (NPRA) genes, and the presence and extent of coronary artery disease (CAD) in Greek patients with a history of myocardial infarction (MI). A total of 158 post-MI patients referred for coronary angiography were compared with 144 controls. The SS genotype of the AGT gene was related with an increased risk for 3-vessel CAD (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.05-3.61; P = .041), whereas the SL genotype was related with a decreased risk (OR, 0.44; 95% CI, 0.22-0.87; P = .019). Moreover, there was a trend for the SL genotype of the REN gene toward increased risk for CAD. There was a significant association between (CA)n polymorphism of the AGT gene and the extent of CAD in Greek patients with a history of MI.

  5. The gender-specific role of polymorphisms from the fibrinolytic, renin-angiotensin, and bradykinin systems in determining plasma t-PA and PAI-I levels

    NARCIS (Netherlands)

    Asselbergs, Folkert W.; Williams, Scott M.; Hebert, Patricia R.; Coffey, Christopher S.; Hillege, Hans L.; Navis, Gerjan; Vaughan, Douglas E.; van Gilst, Wiek H.; Moore, Jason H.

    2006-01-01

    Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor I (PAI-I) directly influence thrombus formation and degradation and thus risk for arterial thrombosis. We report here results from a genetic analysis of plasma t-PA and PAI-I levels in a large population-based sample from the

  6. Renin angiotensin system blockade reduces urinary levels of soluble urokinase plasminogen activator receptor (suPAR) in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, Frederik; Theilade, Simone; Eugen-Olsen, Jesper

    2016-01-01

    treatment periods were compared to placebo. Patients (n = 22) were treated for 2-month periods with either placebo, irbesartan 300 mg once daily, aliskiren 300 mg once daily or irbesartan/aliskiren combination in random order. Placebo geometric mean plasma (SEM) levels of suPAR were 3.3 ng/mL (1.1......) and urine levels were 4.0 ng/mL (1.1). None of the treatments had significant effects on plasma levels of suPAR compared to placebo. Compared to placebo, irbesartan and combination treatment decreased urinary levels of suPAR significantly (-1.3 ng/mL), while aliskiren did not. In patients with type 2......Soluble urokinase plasminogen activator receptor (suPAR) is associated with faster decline in kidney function and the pathogenesis of diabetic nephropathy. However, little is known about the impact of treatment on plasma and urinary levels of suPAR. We aimed to investigate the impact of renin...

  7. Renal targeting of captopril selectively enhances the intrarenal over the systemic effects of ACE inhibition in rats

    Science.gov (United States)

    Haverdings, R Folgert G; Haas, Marijke; Navis, Gerjan; van Loenen-Weemaes, Anne-miek; Meijer, Dirk K F; de Zeeuw, Dick; Moolenaar, Frits

    2002-01-01

    In previous studies on the renal targeting of the ACE inhibitor captopril, we demonstrated that a 6 fold increased concentration of this drug could be obtained in the kidney after conjugation to the low-molecular-weight protein lysozyme. In this study, we investigated in unrestrained rats whether systemic administration of captopril–lysozyme also results in an enhanced effect on renal parameters, relative to the systemic effects. Renal effects: intravenous infusion of captopril–lysozyme for 6 h resulted in a more pronounced increment of renal blood flow (31±2% vs 17±4% at 0.5 mg kg−1 6h−1, Pcaptopril as a free drug. In correspondence with these findings, renal ACE inhibition was potentiated approximately 5 fold (−50±4% vs −22±3% at 1 mg kg−1 6 h−1, Pcaptopril did not affect blood pressure in dosages up to 5 mg kg−1 6 h−1. This effect coincided with a less pronounced inhibition of the pressor response to intravenously administered angiotensin I (−12±3% vs −66±5% at 1 mg kg−1 6 h−1, Pcaptopril. An experiment of continued intravenous administration of captopril–lysozyme for 7 days in nephrotic syndrome demonstrated that the conjugate is also active in renal disease: the antiproteinuric response was substantially augmented (−67±5% vs −15±7% at 4 mg kg−1 24 h−1, Pcaptopril–lysozyme conjugate leads to more selective renal ACE inhibition and enhanced renal effects as well as less systemic effects compared to captopril itself. PMID:12163343

  8. Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria

    OpenAIRE

    Martin-Lorenzo, Marta; Gonzalez-Calero, Laura; Martinez, Paula J.; Baldan-Martin, Montserrat; Lopez, Juan Antonio; Ruiz-Hurtado, Gema; de la Cuesta, Fernando; Segura, Juli?n; Vazquez, Jes?s; Vivanco, Fernando; Barderas, Maria G.; Ruilope, Luis M.; Alvarez-Llamas, Gloria

    2017-01-01

    Albuminuria development in hypertensive patients is an indicator of higher cardiovascular (CV) risk and renal damage. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control but it does not prevent from albuminuria development. We pursued the identification of protein indicators in urine behind albuminuria development in hypertensive patients under RAS suppression. Urine was collected from 100 patients classified in three groups according to albuminuria developme...

  9. Molecule-specific Effects of Angiotensin II–Receptor Blockers Independent of the Renin–Angiotensin System

    Czech Academy of Sciences Publication Activity Database

    Kurtz, T. W.; Pravenec, Michal

    2008-01-01

    Roč. 21, č. 8 (2008), s. 852-859 ISSN 0895-7061 R&D Projects: GA MŠk(CZ) 1M0520; GA MZd(CZ) NR8545 Grant - others:EURATOOLS(XE) LSHG-CT-2005-019015; HHMI(US) 55005624 Institutional research plan: CEZ:AV0Z50110509 Keywords : angiotensin-receptor blockers * cardiovascular protection * renin-angiotensin system Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.122, year: 2008

  10. Traumatic Intrarenal Arteriovenous Fistula Treated by Conservative ...

    African Journals Online (AJOL)

    1974-06-01

    Jun 1, 1974 ... with these vascular lesions.' Varela' in 1928 reported the first case of intrarenal arteriovenous fistula. Arteriovenous fistula of the kidney is an ... and penetrating abdominal trauma, this lesion will be encountered with increasing frequency. Selective renal artery catheterisation aids materially in making the.

  11. Forearm vascular and neuroendocrine responses to graded water immersion in humans

    DEFF Research Database (Denmark)

    Gabrielsen, A.; Videbaek, Regitze; Johansen, L.B.

    2000-01-01

    arginine vasopressin, blood pressure, forearm blood flow, renin-angiotensin system, sympathetic nervous system......arginine vasopressin, blood pressure, forearm blood flow, renin-angiotensin system, sympathetic nervous system...

  12. Intra-renal reflux: A new cause of medullary hyperechogenicity

    Energy Technology Data Exchange (ETDEWEB)

    Diard, F.; Nicolau, A.; Bernard, S.

    1987-02-01

    A 5-month-old infant with untreated severe urinary tract infection and bilateral vesico-ureteral reflux, had diffuse intrarenal reflux and hyperechogenicity of the medulla of two normal sized kidneys. We discuss the hyperechogenicity of the medulla in relationship to the intrarenal reflux.

  13. Renovascular hypertension and intrarenal artery aneurysms in a preschool child

    International Nuclear Information System (INIS)

    Hobbs, David J.; Barletta, Gina-Marie; Bunchman, Timothy E.; Mowry, Jeanne A.

    2009-01-01

    Renovascular hypertension from renal artery aneurysmal formation is a rare complication of fibromuscular dysplasia. Few data exist to direct the management of intrarenal artery aneurysms in pediatric patients. We report the presentation, diagnosis and management of renovascular hypertension and intrarenal aneurysmal disease in a preschool child. (orig.)

  14. Renovascular hypertension and intrarenal artery aneurysms in a preschool child

    Energy Technology Data Exchange (ETDEWEB)

    Hobbs, David J.; Barletta, Gina-Marie; Bunchman, Timothy E. [Michigan State University College of Human Medicine, Grand Rapids, MI (United States); Helen DeVos Children' s Hospital, Pediatric Nephrology, Dialysis and Transplantation, Grand Rapids, MI (United States); Mowry, Jeanne A. [Oregon Health Sciences University, Pediatric Nephrology, Northwest Permanente, P.C. and Doernbecher Children' s Hospital, Portland, OR (United States)

    2009-09-15

    Renovascular hypertension from renal artery aneurysmal formation is a rare complication of fibromuscular dysplasia. Few data exist to direct the management of intrarenal artery aneurysms in pediatric patients. We report the presentation, diagnosis and management of renovascular hypertension and intrarenal aneurysmal disease in a preschool child. (orig.)

  15. Renal hyperfiltration and systemic blood pressure in patients with uncomplicated type 1 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Gary K Yang

    Full Text Available Patients with type 1 diabetes mellitus (DM and renal hyperfiltration also exhibit systemic microvascular abnormalities, including endothelial dysfunction. The effect of renal hyperfiltration on systemic blood pressure (BP is less clear. We therefore measured BP, renal hemodynamic function and circulating renin angiotensin aldosterone system (RAAS mediators in type 1 DM patients with hyperfiltration (n = 36, DM-H, GFR≥135 ml/min/1.73 m(2 or normofiltration (n = 40, DM-N, and 56 healthy controls (HC. Since renal hyperfiltration represents a state of intrarenal RAAS activation, we hypothesized that hyperfiltration would be associated with higher BP and elevated levels of circulating RAAS mediators.BP, glomerular filtration rate (GFR - inulin, effective renal plasma flow (paraaminohippurate and circulating RAAS components were measured in DM-H, DM-N and HC during clamped euglycemia (4-6 mmol/L. Studies were repeated in DM-H and DM-N during clamped hyperglycemia (9-11 mmol/L.Baseline GFR was elevated in DM-H vs. DM-N and HC (167±6 vs. 115±2 and 115±2 ml/min/1.73 m(2, p<0.0001. Baseline systolic BP (SBP, 117±2 vs. 111±2 vs. 109±1, p = 0.004 and heart rate (76±1 vs. 67±1 vs. 61±1, p<0.0001 were higher in DM-H vs. DM-N and HC. Despite higher SBP in DM-H, plasma aldosterone was lower in DM-H vs. DM-N and HC (42±5 vs. 86±14 vs. 276±41 ng/dl, p = 0.01. GFR (p<0.0001 and SBP (p<0.0001 increased during hyperglycemia in DM-N but not in DM-H.DM-H was associated with higher heart rate and SBP values and an exaggerated suppression of systemic aldosterone. Future work should focus on the mechanisms that explain this paradox in diabetes of renal hyperfiltration coupled with systemic RAAS suppression.

  16. Effect of Renin-Angiotensin-Aidosterone System Inhibition, Dietary Sodium Restriction, and/or Diuretics on Urinary Kidney Injury Molecule 1 Excretion in Nondiabetic Proteinuric Kidney Disease : A Post Hoc Analysis of a Randomized Controlled Trial

    NARCIS (Netherlands)

    Waanders, Femke; Vaidya, Vishal S.; van Goor, Harry; Leuvenink, Henri; Damman, Kevin; Hamming, Inge; Bonventre, Joseph V.; Vogt, Liffert; Navis, Gerjan

    Background: Tubulointerstitial damage plays an important role in chronic kidney disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using

  17. Effects of Combined Endothelin A Receptor and Renin-Angiotensin System Blockade on the Course of End-Organ Damage in 5/6 Nephrectomized Ren-2 Hypertensive Rats

    Czech Academy of Sciences Publication Activity Database

    Vaněčková, Ivana; Kujal, P.; Husková, Z.; Vaňourková, Z.; Vernerová, Z.; Čertíková; Chábová, V.; Škaroupková, P.; Kramer, H. J.; Tesař, V.; Červenka, L.

    2012-01-01

    Roč. 35, č. 5 (2012), s. 382-392 ISSN 1420-4096 Institutional research plan: CEZ:AV0Z50110509 Keywords : 5/6 nephrectomy * Endothelin receptor type A * AT1 receptor blocker * end-organ damage * hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.596, year: 2012

  18. Pre- and/or Intra-Operative Prescription of Diuretics, but Not Renin-Angiotensin-System Inhibitors, Is Significantly Associated with Acute Kidney Injury after Non-Cardiac Surgery: A Retrospective Cohort Study.

    Science.gov (United States)

    Tagawa, Miho; Ogata, Ai; Hamano, Takayuki

    2015-01-01

    Pre- and/or intra-operative use of diuretics, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) constitutes a potentially modifiable risk factor for postoperative acute kidney injury (AKI). It has been studied whether use of these drugs predicts AKI after cardiac surgery. The objective of this study was to examine whether administration of these agents was independently associated with AKI after non-cardiac surgery. This was a retrospective observational study. Inclusion criteria were adult patients (age ≥ 18) who underwent non-cardiac surgery under general anesthesia from 2007 to 2009 at Kyoto Katsura Hospital. Exclusion criteria were urological surgery, missing creatinine values, and preoperative dialysis. The exposures of interest were pre- and/or intra-operative use of diuretics or ACE-I/ARB. Outcome variables were postoperative AKI as defined by the AKI Network (increase in creatinine ≥ 0.3 mg/dL or 150% within 48 hours, or urine output 6 hours). Multivariable logistic regression analyses were conducted and adjusted for potential confounders. Propensity scores (PS) for receiving diuretics or ACE-I/ARB therapy were estimated and PS adjustment, PS matching, and inverse probability weighting were performed. There were 137 AKI cases (5.0%) among 2,725 subjects. After statistical adjustment for patient and surgical characteristics, odds (95% CI) of postoperative AKI were 2.07 (1.10-3.89) (p = 0.02) and 0.89 (0.56-1.42) (p = 0.63) in users of diuretics and ACE-I/ARB, respectively, compared with non-users. PS adjustment, PS matching, and inverse probability weighting yielded similar results. The effect size of diuretics was significantly greater in the patients with lower propensity for diuretic use (p for interaction diuretics, but not ACE-I/ARB, was independently associated with postoperative AKI after non-cardiac surgery, especially in patients with low propensity for diuretic use. It might be reasonable to withhold preoperative diuretics in these patients.

  19. Lack of synergism between long-term poor glycaemic control and three gene polymorphisms of the renin angiotensin system on risk of developing diabetic nephropathy in type I diabetic patients

    DEFF Research Database (Denmark)

    Tarnow, L; Kjeld, T; Knudsen, E

    2000-01-01

    AIMS/HYPOTHESIS: Reports on a putative synergism between poor glycaemic control and carriage of the angiotensin II type 1 receptor (AGTR1) C1166-allele and risk of diabetic nephropathy have been conflicting. Therefore, we investigated the interaction between long-term glycaemic control and three...... polymorphisms in the genes coding for AGTR1 (A1166-->C), angiotensin converting enzyme (ACE/ID) and angiotensinogen (M235T) on risk of developing diabetic nephropathy. Furthermore, we investigated the relation between a random measurement and long-term measurements of haemoglobin A1c (HbA1c). METHODS: We...... studied Caucasian patients with Type I (insulin-dependent) diabetes mellitus and nephropathy (120 men 74 women, age 41.1 +/- 9.6 years, diabetes duration 28 +/- 8 years) and long-standing Type I diabetic patients with persistent normoalbuminuria (112 men 69 women, age 42.5 +/- 10.0 years, diabetes...

  20. Antihypertensive and cardiovascular effects of combined blockade of renin-angiotensin system with ACE inhibitor and angiotensin II type 1 receptor blocker in hypertensive patients: A 24-week randomized controlled double-dummy trial

    Directory of Open Access Journals (Sweden)

    Giuseppe Licata

    2010-05-01

    Full Text Available Background. In this study the effects of 24 weeks losartan and ramipril treatment, both alone and in combination, on blood pressure and left ventricular mass (LVM and function, have been evaluated in hypertensives. Methods. 57 hypertensives with stage 1 and 2 essential hypertension were included. After 4 weeks run in, a randomized double-blind, 3 arm, double dummy, independent trial was used. All patients were randomly allocated to 3 treatment arms consisting of losartan (50 mg/daily, ramipril (5 mg/daily, and combined (losartan 50 mg/ramipril 5 mg/daily for 24 weeks. LVM, LVM/h2.7 and other echocardiographic measurements, BUN, creatinine and clearance and potassium were determined after run in and 24 weeks. Results. All groups were comparable for gender, age, BMI, BP and LVM. The prevalence of baseline left ventricular hypertrophy (LVH was not significantly different among 3 groups. At the end of treatment, a significant (p<0.05 reduction in SBP, DBP, MBP, LVM and LVM/h2.7 were observed in all groups. The absolute and percent reduction in LVM/h2.7 were significantly higher in combined than losartan or ramipril groups and also in hypertensives with LVH. No significant change in absolute and percent reduction of SBP, DBP and MBP were found. Conclusions. These data indicate an additional cardioprotective effect of dual blockade of RAS in hypertensive patients with and without left ventricular hypertrophy.

  1. Assessment of the degree of oxidative stress injury, renin-angiotensin system activity and podocyte loss after combined treatment of keto acid with low protein diet for patients with diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Yuan-Hua Xu

    2016-03-01

    Full Text Available Objective: To analyze the degree of oxidative stress injury, RAS activity and podocyte loss after patients with diabetic nephropathy received keto acid combined with low protein diet. Methods: A total of 106 cases of patients with diabetic nephropathy who received hospital treatment in our hospital from September 2012 to July 2015 were selected as research subjects and randomly divided into observation group and control group according to different treatment, each group with 53 cases. Control group received low protein diet treatment alone, observation group received keto acid combined with low protein diet treatment, and then the degree of oxidative stress injury, RAS activity and podocyte loss of two groups were compared. Results: Serum MDA and AOPP levels of observation group after treatment were lower than those of control group, and levels of SOD and T-AOC were higher than those of control group; PRA, Ang栻 and Aldosterone levels of observation group after treatment were lower than those of control group; mRNA expression levels of podocin and synaptopodin in urine sediment of observation group after treatment were lower than those of control group. Conclusion: Keto acid combined with low protein diet treatment for patients with diabetic nephropathy can reduce the degree of oxidative stress injury and RAS activity, decrease podocyte loss and optimize patients’ condition.

  2. Intrarenal Splenosis Diagnosed in an Incidentally Found Left Renal Mass

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    Eliza Lamin

    2015-09-01

    Full Text Available Intrarenal splenosis is very rare and its management is not well established. We present a patient in whom an enhancing left renal mass was incidentally detected on a Computerized tomographic (CT scan, concerning for renal cell carcinoma. However, the lesion was determined to represent intrarenal splenosis, confirmed by Technetium-99m (99mTc sulfur colloid scan and percutaneous biopsy, which revealed splenic tissue. This multimodal approach to diagnosis of an unusual condition spared the patient an invasive procedure.

  3. Tc-99m-DTPA renal scintigraphy and detection of intrarenal reflux

    International Nuclear Information System (INIS)

    Poropat, M.; Basic, M.; Dodig, D.; Batinic, D.; Nizic, Lj.

    1994-01-01

    The intrarenal reflux plays the key role in the etiology of reflux nephropathy and its detection is of utmost importance in evaluating possible damage in kidney with reflux. In 176 kidneys (113 children) with different degree of vesicoureteric reflux (VUR), dynamic renal scintigraphy with Tc-99m-DTPA in zoom mode was performed. From each study 6 functional images of mean time were generated, kidney contour superimposed on each, and time activity curves (TAC) over possible areas of increased mean time were generated. In these study we analyzed only areas of increased mean time over the outer contour of the kidney which corresponds to the renal parenchyma. In later functional images of the mean time we found 53 focal retentions over the part of the kidney which corresponds to the renal cortex (33 in upper, 5 in middle and 15 in lower part of the kidney). TAC-s generated over these areas exhibited a sharp increase of activity on the descending part of the curves. We propose that the return of activity from the collecting system to the kidney cortex represents intrarenal reflux. In our opinion, analysis of functional images of the mean time could be a method for more accurate detection of intrarenal reflux and indicating the children with high risk to acquire renal scarring. (author)

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

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    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.

  5. Amelioration of angiotensin II-induced salt-sensitive hypertension by liver-type fatty acid-binding protein in proximal tubules.

    Science.gov (United States)

    Osaki, Ken; Suzuki, Yusuke; Sugaya, Takeshi; Tanifuji, Chiaki; Nishiyama, Akira; Horikoshi, Satoshi; Tomino, Yasuhiko

    2013-10-01

    Inappropriate activation of the intrarenal renin-angiotensin system induces generation of reactive oxygen species and tubulointerstitial inflammation, which contribute to salt-sensitive hypertension (SSHT). Liver-type fatty acid-binding protein is expressed in proximal tubules in humans, but not in rodents, and may play an endogenous antioxidative role. The objective of the present study was to examine the antioxidative effect of liver-type fatty acid-binding protein on post-angiotensin II SSHT model in transgenic mice with selective overexpression of human liver-type fatty acid-binding protein in the proximal tubules. The transgenic mice showed marked protection against angiotensin II-induced SSHT. Overexpression of tubular liver-type fatty acid-binding protein prevented intrarenal T-cell infiltration and also reduced reactive oxygen species generation, intrarenal renin-angiotensin system activation, and monocyte chemotactic protein-1 expression. We also performed an in vitro study using the murine proximal tubular cell lines with or without recombinant liver-type fatty acid-binding protein and murine proximal tubular cell lines transfected with human liver-type fatty acid-binding protein, and found that gene transfection of liver-type fatty acid-binding protein and, in part, recombinant liver-type fatty acid-binding protein administration had significantly attenuated angiotensin II-induced reactive oxygen species generation and the expression of angiotensinogen and monocyte chemotactic protein-1 in murine proximal tubular cell lines. These findings indicated that liver-type fatty acid-binding protein in the proximal tubules may protect against angiotensin II-induced SSHT by attenuating activation of the intrarenal renin-angiotensin system and reducing oxidative stress and tubulointerstitial inflammation. Present data suggest that liver-type fatty acid-binding protein in the proximal tubules may be a novel therapeutic target for SSHT.

  6. Intrarenal pseudoaneurysm after percutaneous nephrolithotomy: angiotomographic assessment and endovascular management

    Directory of Open Access Journals (Sweden)

    M. F. Massulo-Aguiar

    2006-08-01

    Full Text Available We report a case of intrarenal pseudoaneurysm of the right kidney after percutaneous nephrolithotomy (PCNL in supine position. Diagnosis was established by angiotomography with a 3-D reconstruction. Treatment was successfully achieved by endovascular occlusion using N-butyl-2-cyanoacrylate.

  7. Comparative sonographic evaluation of intra-renal resistive index ...

    African Journals Online (AJOL)

    The intra-renal resistive index is a Doppler parameter that is useful in predicting adult hypertensive patients who are likely to develop nephrosclerosis and to follow up hypertensive patients on reno-protective drugs to determine effects of drugs on renal function. This was a prospective cross-sectional comparative descriptive ...

  8. A simple method to ensure homogeneous drug distribution during intrarenal infusion

    DEFF Research Database (Denmark)

    Postnov, Dmitry D; Salomonsson, Max; Sorensen, Charlotte M

    2017-01-01

    Intrarenal drug infusion plays an important role in renal experimental research. Laminar flow of the blood can cause streaming and inhomogeneous intrarenal distribution of infused drugs. We suggest a simple method to achieve a homogeneous intravascular distribution of drugs infused into the renal...

  9. Retrograde Intrarenal Surgery for Small Renal Calyx Stones

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    Nevzat Sener

    2014-04-01

    Full Text Available Lower pole kidney stones are one of the most common problems is urology practice. For this group of patients, shock wave lithotripsy (SWL and retrograde intrarenal surgery (RIRS are established treatments with low morbidity and high efficacy. SWL has relatively lower success rates for lower pole stones. On the other hand, RIRS has as high as 100% success rates for lower pole stones. With advances in technology and experience we believe RIRS may be the first treatment option over SWL in the following years.

  10. Dynamics of intrarenal pressures and glomerular filtration rate after acetazolamide

    DEFF Research Database (Denmark)

    Leyssac, P P; Karlsen, F M; Skøtt, O

    1991-01-01

    The dynamics of intrarenal pressures, early distal tubular fluid conductivity (EDC), and renal flood flow (RBF) were studied in rats given acetazolamide (ACZ), an inhibitor of proximal reabsorption. Glomerular filtration rate (GFR) and end-proximal flow were estimated by clearances of 51Cr......-EDTA and lithium. Proximal tubular pressure (Pprox) increased initially by 1.7 +/- 0.1 mmHg after ACZ, causing a decrease in the hydrostatic pressure difference across the glomerular membrane (delta P). EDC increased, and then RBF, glomerular capillary pressure (Pgc), Pprox, and star vessel pressures (Psv) dropped...

  11. Nutritional status and intrarenal resistive indices after kidney transplantation.

    Science.gov (United States)

    Kolonko, A; Chudek, J; Kujawa-Szewieczek, A; Wiȩcek, A

    2013-05-01

    Obesity predicts vascular stiffness, which is prevalent among kidney transplant patients. However, the influence of obesity has not been established on parameters of renal vascular resistance variation. The aim of this study was to analyze the influence of nutritional status on intrarenal resistive parameters as measured in the early period after successful kidney transplantation by Doppler ultrasound. Both pulsatility index (PI) and resistance index (RI) in the kidney graft were measured by Doppler sonography twice: at 2 to 4 days and before hospital discharge (mean 22 days; 95% confidence interval 21-23) after transplantation. Nutritional status was scored according to World Health Organization criteria. Among 513 patients, 29 were underweight; 280, normal; 166, overweight; and 38, obese. Both PI and RI values were significantly increased consistent with recipient nutritional status (analysis of variance: P underweight or normal weight groups. Multivariate analysis revealed an influence of body mass index on PI and RI measurements before hospital discharge to be independent of other variables, including recipient age, prior delayed graft function and cold ischemia time. Excessive nutritional status was associated with increased renal vascular resistance among kidney transplant patients. Nutritional status should be considered for the proper interpretation of intrarenal Doppler measurements. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Traumatic Intrarenal Arteriovenous Fistula Treated by Conservative ...

    African Journals Online (AJOL)

    1974-06-01

    Jun 1, 1974 ... Fig. 1. Excretory urogram demonstrating normal renal parenchyma and collecting system. Renal angiogram: Selective right renal artery catheter- isation demonstrated early filling of the right renal vein consistent with an arteriovenous fistula; a small traumatic pseudo-aneurysm; a relatively avascular area in ...

  13. Intra-renal localised reno-renal collaterals in the dog after tying of the main renal artery

    International Nuclear Information System (INIS)

    Rosenbusch, G.; Vincent, J.; Douveren, W. van; Sktonicki, S.; Arts, T.H.M.; Katholieke Univ. Nijmegen; Katholieke Univ. Nijmegen

    1984-01-01

    In 7 kidneys of 6 dogs one of the main stem of the renal artery was ligated. The development of the renorenal collaterals could be followed in 5, as two dogs died after the operation. In all cases intrarenal collaterals could be demonstrated, even in the postoperative dead dogs. The vessels responsible for the collateral circulation are preformed interarterial anastomoses, belonging to the extraglomerular arterial system. From the results of these and former experimental studies it can be concluded, that the renal artery of the dog when entering the renal sinus cannot be regarded as an anatomic, but at most as a functional end artery. (orig.) [de

  14. Intra-renal localised reno-renal collaterals in the dog after tying of the main renal artery

    Energy Technology Data Exchange (ETDEWEB)

    Rosenbusch, G.; Vincent, J.; Douveren, W. van; Sktonicki, S.; Arts, T.H.M.

    1984-01-01

    In 7 kidneys of 6 dogs one of the main stem of the renal artery was ligated. The development of the renorenal collaterals could be followed in 5, as two dogs died after the operation. In all cases intrarenal collaterals could be demonstrated, even in the postoperative dead dogs. The vessels responsible for the collateral circulation are preformed interarterial anastomoses, belonging to the extraglomerular arterial system. From the results of these and former experimental studies it can be concluded, that the renal artery of the dog when entering the renal sinus cannot be regarded as an anatomic, but at most as a functional end artery.

  15. Exploration by radioactive fibrinogen of intrarenal coagulation phenomena. Preliminary results

    International Nuclear Information System (INIS)

    Simon, Jacques.

    1974-01-01

    The participation of fibrin deposits in kidney pathology was studied by the use of a radioactive tracer involved in the coagulation phenomenon: iodine 131-labelled fibrinogen. The isotopic exploration consists of a fibrinogen kinetics study combined with external counting over the kidney regions. The different stages of the procedure are described: separation, purification and labelling of fibrinogen; characteristics of the radioactive fibrinogen used; practical details of the examination itself; data analysis method. A chapter devoted to verifications and discussions of the procedure is followed by a report on the exploration of intrarenal coagulation phenomena in 30 kidney disease patients. In conclusion, the study of fibrinogen kinetics is considered as the most suitable method to detect local or slight intravascular coagulation phenomena. The sensitivity of the isotopic exploration is very satisfactory. The main criticism directed against this method is that the exploration is general and therefore blind [fr

  16. How does obesity affect the endocrine system? A narrative review.

    Science.gov (United States)

    Poddar, M; Chetty, Y; Chetty, V T

    2017-06-01

    Obesity is a chronic, relapsing medical condition that results from an imbalance of energy expenditure and consumption. It is a leading cause of preventable illness, disability and premature death. The causes of obesity are multifactorial and include behavioural, socioeconomic, genetic, environmental and psychosocial factors. Rarely are endocrine diseases, e.g., hypothyroidism or Cushing's syndrome, the cause of obesity. What is less understood is how obesity affects the endocrine system. In this review, we will discuss the impact of obesity on multiple endocrine systems, including the hypothalamic-pituitary axis, changes in vitamin D homeostasis, gender steroids and thyroid hormones. We will also examine the renin angiotensin aldosterone system and insulin pathophysiology associated with obesity. We will provide a general overview of the biochemical changes that can be seen in patients with obesity, review possible aetiologies of these changes and briefly consider current guidelines on their management. This review will not discuss endocrine causes of obesity. © 2017 World Obesity Federation.

  17. Angiotensinogen and ACE gene polymorphisms and risk of atrial fibrillation in the general population

    DEFF Research Database (Denmark)

    Ravn, Lasse Steen; Benn, Marianne; Nordestgaard, Børge

    2008-01-01

    Objectives The renin-angiotensin system may play a role in the pathogenesis of atrial fibrillation, and renin-angiotensin system blockers reduce the risk of atrial fibrillation. We hypothesized that polymorphisms in the angiotensinogen and angiotensin-converting enzyme (ACE) genes encoding protei...

  18. Antihypertensive effects of double the maximum dose of valsartan in African-American patients with type 2 diabetes mellitus and albuminuria

    DEFF Research Database (Denmark)

    Weir, Matthew R; Hollenberg, Norman K; Zappe, Dion H

    2010-01-01

    The blood pressure (BP)-lowering response to renin-angiotensin-aldosterone system blockade in hypertensive African-Americans is typically less than in whites. To determine whether higher than conventional doses of renin-angiotensin-aldosterone system blockade can improve BP reduction in African-A...

  19. Effect of valsartan on the incidence of diabetes and cardiovascular events

    DEFF Research Database (Denmark)

    McMurray, John J; Holman, Rury R; Haffner, Steven M

    2010-01-01

    It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance.......It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance....

  20. Non-Traditional Systemic Treatments for Diabetic Retinopathy: An
Evidence-Based Review

    Science.gov (United States)

    Simó, Rafael; Ballarini, Stefania; Cunha-Vaz, José; Ji, Linong; Haller, Hermann; Zimmet, Paul; Wong, Tien Y.

    2015-01-01

    The rapid escalation in the global prevalence diabetes, with more than 30% being afflicted with diabetic retinopathy (DR), means it is likely that associated vision-threatening conditions will also rise substantially. This means that new therapeutic approaches need to be found that go beyond the current standards of diabetic care, and which are effective in the early stages of the disease. In recent decades several new pharmacological agents have been investigated for their effectiveness in preventing the appearance and progression of DR or in reversing DR; some with limited success while others appear promising. This up-to-date critical review of non-traditional systemic treatments for DR is based on the published evidence in MEDLINE spanning 1980-December 2014. It discusses a number of therapeutic options, paying particular attention to the mechanisms of action and the clinical evidence for the use of renin-angiotensin system blockade, fenofibrate and calcium dobesilate monohydrate in DR. PMID:25989912

  1. Relationship Between Serum Uric Acid Levels and Intrarenal Hemodynamic Parameters

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    Hideki Uedono

    2015-06-01

    Full Text Available Background/Aims: Hyperuricemia has been reported to affect renal hemodynamics in rat models. We evaluate the relationship between serum uric acid and intrarenal hemodynamic parameters in humans, utilizing the plasma clearance of para-aminohippurate (CPAH and inulin (Cin. Methods: Renal and glomerular hemodynamics were assessed by simultaneous measurement of CPAH and Cin in 58 subjects. Of these, 19 subjects were planned to provide a kidney for transplantation; 26 had diabetes without proteinuria; and 13 had mild proteinuria. Renal and glomerular hemodynamics were calculated using Gomez`s formulae. Results: Cin was more than 60 ml/min/1.73m2 in all subjects. Serum uric acid levels correlated significantly with vascular resistance at the afferent arteriole (Ra (r = 0.354, p = 0.006 but not with that of the efferent arteriole (Re. Serum uric acid levels (β = 0.581, p = a after adjustment for several confounders (R2 = 0.518, p = Conclusions: These findings suggest, for the first time in humans, that higher serum uric acid levels are associated significantly with Ra in subjects with Cin > 60 ml/min/1.73m2. The increase in Ra in subjects with higher uric acid levels may be related to dysfunction of glomerular perfusion.

  2. Intraparenchymal hematoma as a late complication of retrograde intrarenal surgery

    Directory of Open Access Journals (Sweden)

    Sedat Yahsi

    Full Text Available ABSTRACT A 34 year-old woman was admitted to our hospital with left flank pain. A non-contrast enhanced computerized tomography (NCCT revealed a 1.5x2cm left proximal ureter stone. Patient was scheduled for ureterorenoscopy (URS and stone removal. She was submitted to retrograde intrarenal surgery (RIRS. At the postoperative 1st day, the patient began to suffer from left flank pain. A NCCT was taken, which revealed a subcapsular hematoma and perirenal fluid. The patient was managed conservatively with intravenous fluid, antibiotic and non-steroidal anti-inflammatory drug therapy and was discharged at the postoperative 6th day. Two weeks after the discharge the patient was admitted to emergency department with severe left flank pain, palpitation and malaise. KUB (kidney-ureter-bladder radiography showed double-J stent (DJS to be repositioned to the proximal ureter. Patient was evaluated with contrast enhanced CT which revealed an 8cm intraparenchymal hematoma/abscess in the middle part of the kidney. A percutaneous drainage catheter was inserted into the collection. The percutaneous drainage catheter and the DJS were removed at the 10th day of second hospitalization. RIRS surgery is an effective and feasible choice for renal stones with high success and acceptable complication rates. However, clinician should be alert to possible complications.

  3. Intrarenal neuroblastoma - a diagnostic dilemma: A report of three cases

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    Anupam Lall

    2001-01-01

    Full Text Available Differentiation between the Wilms′ tumor (WT and the intrarenal neuroblastoma (IRNB is imperative, as the prognosis and the treatment are different for these condi-tions. It may pose a diagnostic challenge to distinguish them pre-operatively. Over the period of last 10 years (1990-1999, 3 children aged 2 months to 4 years were diagnosed to have IRNB. 2 cases were operated with a provisional diagnosis of WT, but on histology were found to have neuroblastoma. Taking benefit from our previous experience, the third case we encountered with a renal lump and bony metastasis with clinical features not con-sistent with the diagnosis of Wilms′ tumor was further investigated. Urinary catecholamines were significantly elevated and there was bone marrow involvement and positive bone scan for multiple bony metastasis. 2 pa-tients are on chemotherapy and follow-up for last 6 months, while 1 died 6 years back after a follow-up of 2 years. Patients who have a renal mass on imaging, with clinical features of rapid deterioration in general condi-tion and evidence of bony secondaries, should undergo work-up for neuroblastoma pre-operatively to confirm the diagnosis.

  4. Our Retrograde Intrarenal Surgery Experience with Horseshoe Kidney

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    Tufan Süelözgen

    2017-09-01

    Full Text Available Objective: To share our experience with retrograde intrarenal surgery (RIRS done in patients with horseshoe kidney anomaly. Materials and Methods: Data from 107 patients who underwent RIRS for kidney stones between 2013 and 2016 in our clinic was retrospectively analyzed and 6 patients with horseshoe kidney anomaly detected on computed tomography (CT were included in the study. Achieving stone-free status or having residual stones of ≤4 mm were considered operational success. Results: The mean age of the patients was 44.5±6.7 years. Four patients were male (66.6% and two were female (33.3%. The mean stone size was 14.5±4.1 (10-22 mm. Three patients had pelvis stones (50% and the rest 3 (50% had lower calyx stones. Two patients (33.3% were found to be stone-free on post-operative non-contrast CT results. Conclusion: RIRS should be performed by experienced surgeons in patients with horseshoe kidney.

  5. Role of the inhibitors of angiotensin renin system on the DNA integrity of irradiated spermatozoids

    International Nuclear Information System (INIS)

    Spadella, Maria A.; Mansano, Naira S.; Schwarz, Franciele C.; Viani, Gustavo A.; Chies, Agnaldo B.

    2016-01-01

    Radiation action in the testes can significantly affect the reproductive capacity due to oxidative stress generated; phenomenon in which there is evidence of involvement of the Renin Angiotensin System (RAS). This study evaluated the role of AT1 receptor inhibitors, in mitigating the radioinduced DNA damage sperm from semen samples left vas deferens. Male Wistar rats were divided into six experimental groups: Control, 5Gy, Telmisartan (12mg/kg/day) and Losartan (34mg/kg/2x/day), 5 Gy + Telmisartan and 5 Gy + Losartan. The results showed increase in the percentage of sperm with fragmented DNA in irradiated groups when compared to controls, which was not reversed in the irradiated and treated groups. The radiation of 5Gy (single dose) affected the DNA-protein complex of the sperm and the treatments did not influence in reversing this damage, considering the experimental protocol used. (author)

  6. Blockade of Rennin-Angiotensin system blunts the fibrotic response in experimental acute pyelonephritis

    Directory of Open Access Journals (Sweden)

    Singal A

    2005-01-01

    Full Text Available Aim: To study the impact of Renin-Angiotensin system blockade in experimental acute pyelonephritis, induced by a novel surgical approach via dorsal lumbotomy incision. Materials and Methods : 45 Adult female WISTAR rats aged 8-12 weeks, underwent direct inoculation of 0.1 ml of E.coli suspension into the parenchyma of the surgically exposed kidney. 3 groups of rats were studied: Group A - treated with antibiotics only; Group B- Captopril and antibiotics and Group C- Losartan and antibiotics. Changes of acute inflammation, parenchymal destruction and scarring were compared between the groups on histopathological sections. Kruskal-Wallis test was used for statistical analysis. Results : Changes consistent with acute pyelonephritis were seen in all the kidneys. Mean% scar area in Group A, Group B and Group C was 37.08±1.79, 24.40±1.88 and 24.68±1.32% respectively at end of six weeks. Mean tubular density in Group A, B and C was 17.26±1.92, 47.18±3.00 and 47.00±5.08-tubules/lac mm2 respectively. The differences between the control and the treated animals were significant, though the results did not differ between the losartan and captopril treated rats. Conclusions : Dorsal lumbotomy approach to the kidney provides a good exposure of the kidney. Induction of acute pyelonephritis by direct inoculation of bacteria into renal cortex produced a consistent scar at 6 weeks. Blockade of renin angiotensin system by either captopril or losartan decreased the renal scar area by almost 1/3 at 6 weeks.

  7. Is routine ureteral stenting really necessary after retrograde intrarenal surgery?

    Directory of Open Access Journals (Sweden)

    Ekrem Ozyuvali

    2015-03-01

    Full Text Available Objectives: To investigate the situations in which ureteral double-J stent should be used after retrograde intrarenal surgery (RIRS. Patients and Methods: Patients with no ureteral double-J stent after RIRS constituted Group 1, and those with double- J stent after RIRS constituted Group 2. Patients’ age and gender, renal stone characteristics (location and dimension, stone-free status, VAS score 8 hours after surgery, post-procedural renal colic attacks, length of hospitalization, requirement for re-hospitalization, time to rehospitalization and secondary procedure requirements were analyzed. Results: RIRS was performed on 162 renal units. Double-J stent was used in 121 (74.6% of these after RIRS, but not in the other 41 (25.4%. At radiological monitoring at the first month postoperatively after RIRS, complete stone-free status was determined in 122 (75.3% renal units, while residual stone was present in 40 (24.6%. No significant differences were observed between the groups in terms of duration of fluoroscopy (p = 0.142, operation (p = 0.108 or hospitalization times (p = 0.798. VAS values determined routinely on the evening of surgery were significantly higher in Group 1 than in Group 2 (p = 0.025. Twenty-eight (17.2% presentations were made to the emergency clinic due to renal colic within 1 month after surgery. Double-J catheter was present in 24 (85.7% of these patients. Conclusions: Routine double-J stent insertion after RIRS is not essential since it increases costs, morbidity and operation time.

  8. Comparative Effects of Direct Renin Inhibitor and Angiotensin Receptor Blocker on Albuminuria in Hypertensive Patients with Type 2 Diabetes. A Randomized Controlled Trial.

    Science.gov (United States)

    Uzu, Takashi; Araki, Shin-Ichi; Kashiwagi, Atsunori; Haneda, Masakazu; Koya, Daisuke; Yokoyama, Hiroki; Kida, Yasuo; Ikebuchi, Motoyoshi; Nakamura, Takaaki; Nishimura, Masataka; Takahara, Noriko; Obata, Toshiyuki; Omichi, Nobuyuki; Sakamoto, Katsuhiko; Shingu, Ryosuke; Taki, Hideki; Nagai, Yoshio; Tokuda, Hiroaki; Kitada, Munehiro; Misawa, Miwa; Nishiyama, Akira; Kobori, Hiroyuki; Maegawa, Hiroshi

    2016-01-01

    In patients with diabetes, albuminuria is a risk marker of end-stage renal disease and cardiovascular events. An increased renin-angiotensin system activity has been reported to play an important role in the pathological processes in these conditions. We compared the effect of aliskiren, a direct renin inhibitor (DRI), with that of angiotensin receptor blockers (ARBs) on albuminuria and urinary excretion of angiotensinogen, a marker of intrarenal renin-angiotensin system activity. We randomly assigned 237 type 2 diabetic patients with high-normal albuminuria (10 to albuminuria. Twelve patients dropped out during the observation period, and a total of 225 patients were analyzed. During the study period, the systolic and diastolic blood pressures were not different between the groups. The changes in the urinary albumin-to-creatinine ratio from baseline to the end of the treatment period in the DRI and ARB groups were similar (-5.5% and -6.7%, respectively). In contrast, a significant reduction in the urinary excretion of angiotensinogen was observed in the ARB group but not in the DRI group. In the subgroup analysis, a significant reduction in the albuminuria was observed in the ARB group but not in the DRI group among high-normal albuminuria patients. DRI and ARB reduced albuminuria in hypertensive patients with type 2 diabetes. In addition, ARB, but not DRI, reduced albuminuria even in patients with normal albuminuria. DRI is not superior to ARB in the reduction of urinary excretion of albumin and angiotensinogen.

  9. Overexpression of the neuronal human (pro)renin receptor mediates angiotensin II-independent blood pressure regulation in the central nervous system.

    Science.gov (United States)

    Peng, Hua; Jensen, Dane D; Li, Wencheng; Sullivan, Michelle N; Buller, Sophie A; Worker, Caleb J; Cooper, Silvana G; Zheng, Shiqi; Earley, Scott; Sigmund, Curt D; Feng, Yumei

    2018-03-01

    Despite advances in antihypertensive therapeutics, at least 15-20% of hypertensive patients have resistant hypertension through mechanisms that remain poorly understood. In this study, we provide a new mechanism for the regulation of blood pressure (BP) in the central nervous system (CNS) by the (pro)renin receptor (PRR), a recently identified component of the renin-angiotensin system that mediates ANG II formation in the CNS. Although PRR also mediates ANG II-independent signaling, the importance of these pathways in BP regulation is unknown. Here, we developed a unique transgenic mouse model overexpressing human PRR (hPRR) specifically in neurons (Syn-hPRR). Intracerebroventricular infusion of human prorenin caused increased BP in Syn-hPRR mice. This BP response was attenuated by a NADPH oxidase (NOX) inhibitor but not by antihypertensive agents that target the renin-angiotensin system. Using a brain-targeted genetic knockdown approach, we found that NOX4 was the key isoform responsible for the prorenin-induced elevation of BP in Syn-hPRR mice. Moreover, inhibition of ERK significantly attenuated the increase in NOX activity and BP induced by human prorenin. Collectively, our findings indicate that an ANG II-independent, PRR-mediated signaling pathway regulates BP in the CNS by a PRR-ERK-NOX4 mechanism. NEW & NOTEWORTHY This study characterizes a new transgenic mouse model with overexpression of the human (pro)renin receptor in neurons and demonstrated a novel angiotensin II-independent mechanism mediated by human prorenin and the (pro)renin receptor in the central regulation of blood pressure.

  10. Retrograd intrarenal stenkirurgi--en minimalinvasiv metode til behandling af nyresten

    DEFF Research Database (Denmark)

    Jung, Helene U; Osther, Palle J S

    2009-01-01

    Retrograde intrarenal stone surgery (RIRS) is a safe and effective minimally invasive method for the treatment of minor (kidney stones. This modality is the preferred treatment for minor ESWL-resistant kidney stones where resistance is due e.g. to anatomical abnormalities or stones...

  11. Retrograde intrarenal stone surgery for extracorporeal shock-wave lithotripsy-resistant kidney stones

    DEFF Research Database (Denmark)

    Jung, Helene; Nørby, Bettina; Osther, Palle Jörn

    2006-01-01

    OBJECTIVE: The newer flexible ureteroscopes, 150-200-microm holmium YAG laser fibres and superflexible Dormia baskets have made it possible to reach and treat stones in all parts of the kidney. The object of this evaluation was to study the outcome of retrograde intrarenal stone surgery (RIRS...

  12. Aging has small effects on initial ischemic acute kidney injury development despite changing intrarenal immunologic micromilieu in mice.

    Science.gov (United States)

    Jang, Hye Ryoun; Park, Ji Hyeon; Kwon, Ghee Young; Park, Jae Berm; Lee, Jung Eun; Kim, Dae Joong; Kim, Yoon-Goo; Kim, Sung Joo; Oh, Ha Young; Huh, Wooseong

    2016-02-15

    Inflammatory process mediated by innate and adaptive immune systems is a major pathogenic mechanism of renal ischemia-reperfusion injury (IRI). There are concerns that organ recipients may be at increased risk of developing IRI after receiving kidneys from elder donors. To reveal the effects of aging on the development of renal IRI, we compared the immunologic micromilieu of normal and postischemic kidneys from mice of three different ages (9 wk, 6 mo, and 12 mo). There was a higher number of total T cells, especially effector memory CD4/CD8 T cells, and regulatory T cells in the normal kidneys of old mice. On day 2 after IRI, the proportion of necrotic tubules and renal functional changes were comparable between groups although old mice had a higher proportion of damaged tubule compared with young mice. More T cells, but less B cells, trafficked into the postischemic kidneys of old mice. The infiltration of NK T cells was similar across the groups. Macrophages and neutrophils were comparable between groups in both normal kidneys and postischemic kidneys. The intrarenal expressions of TNF-α and VEGF were decreased in normal and postischemic kidneys of aged mice. These mixed effects of aging on lymphocytes and cytokines/chemokines were not different between the two groups of old mice. Our study demonstrates that aging alters the intrarenal micromilieu but has small effects on the development of initial renal injury after IRI. Further study investigating aging-dependent differences in the repair process of renal IRI may be required. Copyright © 2016 the American Physiological Society.

  13. CT Findings of Intrarenal Yolk Sac Tumor with Tumor Thrombus Extending into the Inferior Vena Cava: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Shao Chun; Li, Xue Hua; Sun, Can Hui; Feng, Shi Ting; Peng, Zhen Peng; Huang, Si Yun; Li, Zi Ping [Dept. of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China)

    2014-10-15

    Yolk sac tumor (YST) is a rare germ cell neoplasm of childhood that usually arises from the testis or ovary. The rare cases of YST in various extragonadal locations have been reported, but the primary intrarenal YST is even more uncommon. Here, we report a case of a primary intrarenal YST with tumor thrombus of the inferior vena cava and left renal vein in a 2-year-old boy, with an emphasis on the CT features. To our knowledge, this is the first reported case of an intrarenal YST with intravascular involvement.

  14. Role of the inhibitors of angiotensin renin system on the DNA integrity of irradiated spermatozoids; Papel dos inibidores dos sistema renina angiotensina sobre a integridade do DNA de espermatozoides irradiados

    Energy Technology Data Exchange (ETDEWEB)

    Spadella, Maria A.; Mansano, Naira S.; Schwarz, Franciele C.; Viani, Gustavo A.; Chies, Agnaldo B. [Faculdade de Medicina de Marilia (FAMEMA), Marilia, SP (Brazil)

    2016-07-01

    Radiation action in the testes can significantly affect the reproductive capacity due to oxidative stress generated; phenomenon in which there is evidence of involvement of the Renin Angiotensin System (RAS). This study evaluated the role of AT1 receptor inhibitors, in mitigating the radioinduced DNA damage sperm from semen samples left vas deferens. Male Wistar rats were divided into six experimental groups: Control, 5Gy, Telmisartan (12mg/kg/day) and Losartan (34mg/kg/2x/day), 5 Gy + Telmisartan and 5 Gy + Losartan. The results showed increase in the percentage of sperm with fragmented DNA in irradiated groups when compared to controls, which was not reversed in the irradiated and treated groups. The radiation of 5Gy (single dose) affected the DNA-protein complex of the sperm and the treatments did not influence in reversing this damage, considering the experimental protocol used. (author)

  15. Fetal programming of renal function.

    Science.gov (United States)

    Dötsch, Jörg; Plank, Christian; Amann, Kerstin

    2012-04-01

    Results from large epidemiological studies suggest a clear relation between low birth weight and adverse renal outcome evident as early as during childhood. Such adverse outcomes may include glomerular disease, hypertension, and renal failure and contribute to a phenomenon called fetal programming. Other factors potentially leading to an adverse renal outcome following fetal programming are maternal diabetes mellitus, smoking, salt overload, and use of glucocorticoids during pregnancy. However, clinical data on the latter are scarce. Here, we discuss potential underlying mechanisms of fetal programming, including reduced nephron number via diminished nephrogenesis and other renal (e.g., via the intrarenal renin-angiotensin-aldosterone system) and non-renal (e.g., changes in endothelial function) alterations. It appears likely that the outcomes of fetal programming may be influenced or modified postnatally, for example, by the amount of nutrients given at critical times.

  16. Utility of Flexible Ureterorenoscopy and Laser Lithotripsy in the Treatment of Multiple Intrarenal Stones

    Directory of Open Access Journals (Sweden)

    Hasan Yılmaz

    2017-09-01

    Full Text Available Objective: We aimed to determine the safety and efficacy of flexible ureterorenoscopy and Holmium laser lithotripsy in treating multiple intrarenal stones. Materials and Methods: We identified 32 consecutive patients with multiple intrarenal stones who underwent flexible ureterorenoscopy and/or laser lithotripsy performed by a single surgeon. Informed consent was obtained from all participants before treatment. Each patient was evaluated in terms of stone location, stone number, stone size, stone burden (cumulative stone length, body mass index, operative time, stone-free rate, and perioperative complications. Results: The median age of the patients was 38 years [interquartile range (IQR, 34.25-52.00]. The patients had a total of 75 intrarenal calculi. The average number of stones per patient was 2.50 (IQR, 2.0-3.0. The median total stone burden per patient was 23.0 mm (IQR, 19.0-28.0 mm. Twenty-one patients (65.5% had stone burdens >20 mm, and 11 (34.5% had burdens ≤20 mm. The overall final stone-free rate was 78.1%. The stone-free rates for patients with stone burdens ≤20 mm and >20 mm were 81.8% (9/11 and 76.2% (16/21, respectively (p=0.544. A perioperative complication (urinary leakage occurred in one patient. Postoperative complications were recorded in four (12.5% patients; a urinary tract infection in one, pain requiring parenteral medication in two, and hematuria in one. Conclusion: Flexible ureterorenoscopy combined with laser lithotripsy may be an effective treatment option for patients with multiple intrarenal stones; we noted only a few minor complications. The success rate was higher in patients with stone burdens ≤20 mm.

  17. 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...

  18. Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers

    NARCIS (Netherlands)

    Heerspink, H. J. L.; Johnsson, E.; Gause-Nilsson, I.; Cain, V. A.; Sjostrom, C. D.

    Aims: To characterize the effect of dapagliflozin on albuminuria and estimated glomerular filtration rate (eGFR) and to determine whether effects on albuminuria were mediated through changes in glycated haemoblogin (HbA1c), systolic blood pressure (SBP), body weight or eGFR. Methods: We conducted a

  19. 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...

  20. Drug: D05147 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available atriuretic peptide (BNP) [HSA:4879] Renin-angiotensin system antagonist Treatment of congestive heart fail...ure NPR1 [HSA:4881] [KO:K12323] ... CAS: 124584-08-3 PubChem: 47206871 ...

  1. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease

    DEFF Research Database (Denmark)

    de Zeeuw, Dick; Akizawa, Tadao; Audhya, Paul

    2013-01-01

    Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown....

  2. Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: A systematic review and meta-analysis

    NARCIS (Netherlands)

    Currie, G. (Gemma); Taylor, A.H.M. (Alison H. M.); Fujita, T. (Toshiro); Ohtsu, H. (Hiroshi); Lindhardt, M. (Morten); K. Rossing; Boesby, L. (Lene); Edwards, N.C. (Nicola C.); Ferro, C.J. (Charles J.); J. Townend (Jonathan); A.H. van den Meiracker (Anton); Saklayen, M.G. (Mohammad G.); Oveisi, S. (Sonia); Jardine, A.G. (Alan G.); C. Delles (Christian); Preiss, D.J. (David J.); Mark, P.B. (Patrick B.)

    2016-01-01

    textabstractBackground: Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease.

  3. The complex field of interplay between vasoactive agents

    DEFF Research Database (Denmark)

    Hansen, Pernille B

    2009-01-01

    Lai et al. provide important new information regarding the interaction between the sympathetic and renin-angiotensin systems in the regulation of glomerular afferent arteriolar contractility. Their study demonstrates a calcium-independent enhanced contractile response to angiotensin II following ...

  4. At 1 antagonism and renin inhibition in mice: Pivotal role of targeting angiotensin II in chronic kidney disease

    NARCIS (Netherlands)

    C. Fraune (Christoph); S. Lange (Simon); C. Krebs (Christian); A. Hölzel (Alexandra); J. Baucke (Jana); N. Divac (Nevena); E. Schwedhelm (Edzard); T. Streichert (Thomas); J. Velden (Joachim); I.M. Garrelds (Ingrid); A.H.J. Danser (Jan); A.-R. Frenay (Anne-Roos); H. van Goor (Harry); J.A. Jankowski (Janusz Antoni); R. Stahl (Rolf); G. Nguyen (Genevieve); U. Wenzel (Ulrich)

    2012-01-01

    textabstractThe role of the renin-angiotensin system in chronic kidney disease involves multiple peptides and receptors. Exerting antipodal pathophysiological mechanisms, renin inhibition and AT 1 antagonism ameliorate renal damage. However, it is unclear which mechanism exerts better

  5. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials

    DEFF Research Database (Denmark)

    Chaturvedi, N.; Porta, M.; Klein, R.

    2008-01-01

    BACKGROUND: Results of previous studies suggest that renin-angiotensin system blockers might reduce the burden of diabetic retinopathy. We therefore designed the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme to assess whether candesartan could reduce the incidence and progression of ...

  6. The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy

    DEFF Research Database (Denmark)

    de Zeeuw, Dick; Coll, Blai; Andress, Dennis

    2014-01-01

    Despite optimal treatment, including renin-angiotensin system (RAS) inhibitors, patients with type 2 diabetic nephropathy have high cardiorenal morbidity and mortality related to residual albuminuria. We evaluated whether or not atrasentan, a selective endothelin A receptor antagonist, further re...

  7. A cornerstone of heart failure treatment is not effective in experimental right ventricular failure

    NARCIS (Netherlands)

    Borgdorff, Marinus A.; Bartelds, Beatrijs; Dickinson, Michael G.; Steendijk, Paul; Berger, Rolf M. F.

    2013-01-01

    Background: Right ventricular (RV) failure due to increased pressure load causes significant morbidity and mortality in patients with congenital heart diseases and pulmonary arterial hypertension. It is unknown whether renin-angiotensin-aldosterone-system (RAAS) inhibition (the cornerstone of left

  8. Rationale and design of a study to evaluate management of proteinuria in patients at high risk for vascular events : the IMPROVE trial

    NARCIS (Netherlands)

    Bakris, G. L.; Ruilope, L.; Locatelli, F.; Ptaszynska, A.; Pieske, B.; Raz, I.; Voors, A. A.; Dechamplain, J.; Weber, M. A.

    Declining kidney function predicts increasing cardiovascular risk in people with hypertension. Microalbuminuria is a marker for cardiovascular risk and declining kidney function. Agents that block the renin-angiotensin-aldosterone system (RAAS), notably angiotensin-converting enzyme (ACE) inhibitors

  9. Retrograde intrarenal surgery and micro-percutaneous nephrolithotomy for renal lithiasis smaller than 2 CM.

    Science.gov (United States)

    Cepeda, M; Amón, J H; Mainez, J A; de la Cruz, B; Rodríguez, V; Alonso, D; Martínez-Sagarra, J M

    2017-10-01

    Microperc is the upgraded form of percutaneous nephrolithotomy miniaturization. The aim of this study is to compare prospectively microperc and retrograde intrarenal surgery for the treatment of renal stones smaller than 2 cm. A comparative prospective study of both techniques was carried out between January 2014 and June 2015. Thirty-five patients were divided in two groups: Group A, 17 patients treated by retrograde intrarenal surgery and Group B, 18 patients treated by microperc. Stone clearance was assessed using CT scan 3 months after surgery. Both groups were statistically comparable as demographic variables and stone size was similar (16.76 mm Group A vs 15.72 mm Group B). Success rate, hospital stay and JJ stenting were similar for both groups. There was no statistically significant difference regarding post-operatory complications: 17.64% Group A vs 5.56% Group B (p=0,062), all of them Clavien I and II. Surgical time was statistically different (63.82 min Group A vs 103.24 min Group B) as well as hemoglobin drop (0.62 g/dl Group A and 1.89 g/dl Group B). Microperc is an effective and safe procedure for the treatment of renal lithiasis smaller than 2 cm, which makes it a good alternative to retrograde intrarenal surgery for this stone size. However, more prospective studies that include a larger cohort are necessary to confirm our results. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Chronic intrarenal insulin replacement reverses diabetes mellitus-induced natriuresis and diuresis.

    Science.gov (United States)

    Manhiani, M Marlina; Duggan, A Daniel; Wilson, Hunter; Brands, Michael W

    2012-02-01

    We showed recently that sustained natriuresis in type 1 diabetic dogs was attributed to the decrease in insulin rather than the hyperglycemia alone. The sodium-retaining action of insulin appeared to require hyperglycemia, and it completely reversed the diabetic natriuresis and diuresis. This study tested whether the sodium-retaining effect was attributed to direct intrarenal actions of insulin. Alloxan-treated dogs (D; n=7) were maintained normoglycemic using 24-h/d IV insulin replacement. After control measurements, IV insulin was decreased to begin a 6-day diabetic period. Blood glucose increased from 84±6 mg/dL to an average of 428 mg/dL on days 5 and 6, sodium excretion increased from 74±8 to 98±7 meq/d over the 6 days, and urine volume increased from 1645±83 to 2198±170 mL/d. Dir dogs (n=7) were subjected to the same diabetic regimen, but, in addition, insulin was infused continuously into the renal artery at 0.3 mU/kg per minute during the 6-day period. This did not affect plasma insulin. Blood glucose increased from 94±10 mg/dL to an average of 380 mg/dL on days 5 and 6, but sodium excretion averaged 76±5 and 69±8 meq/d during control and diabetes mellitus, respectively. The diuresis also was prevented. Glomerular filtration rate increased only in Dir dogs, and there was no change in mean arterial pressure in either group. This intrarenal insulin infusion had no effect on sodium or volume excretion in normal dogs. Intrarenal insulin replacement in diabetic dogs caused a sustained increase in tubular reabsorption that completely reversed diabetic natriuresis. Insulin plus glucose may work to prevent salt wasting in uncontrolled type 2 diabetes mellitus.

  11. Retrograde intrarenal surgery versus percutaneous lithotripsy to treat renal stones 2-3 cm in diameter.

    Science.gov (United States)

    Zengin, Kursad; Tanik, Serhat; Karakoyunlu, Nihat; Sener, Nevzat Can; Albayrak, Sebahattin; Tuygun, Can; Bakirtas, Hasan; Imamoglu, M Abdurrahim; Gurdal, Mesut

    2015-01-01

    Retrograde intrarenal surgery (RIRS) performed using a flexible ureterorenoscope marked the beginning of a new era in urology. Today, even staghorn stones are successfully treated via RIRS. The recommended treatment for larger stones is percutaneous nephrolithotomy (PNL). However, the question of whether PNL or RIRS should be the first-line treatment option for larger stones remains controversial. In this study, we contribute to the debate by comparing the success and complication rates of PNL and RIRS that were used to treat renal pelvis stones 2-3 cm in diameter. The medical records of 154 patients (74 PNL, 80 RIRS) were retrospectively evaluated. PNL patients were placed in Group 1 and RIRS patients in Group 2. The complete stone-free rates were 95.5% in the PNL group and 80.6% in the RIRS group 1 month postoperatively (P = 0.061). The respective complication rates (evaluated using the Clavien system) were 13.5% and 8.8% (P = 0.520). RIRS affords a comparable success rate, causes fewer complications than PNL, and seems to be a promising alternative to PNL when larger stones are to be treated. Prospective randomized controlled trials are needed to confirm these findings.

  12. Retrograde Intrarenal Surgery versus Percutaneous Lithotripsy to Treat Renal Stones 2-3 cm in Diameter

    Directory of Open Access Journals (Sweden)

    Kursad Zengin

    2015-01-01

    Full Text Available Objective. Retrograde intrarenal surgery (RIRS performed using a flexible ureterorenoscope marked the beginning of a new era in urology. Today, even staghorn stones are successfully treated via RIRS. The recommended treatment for larger stones is percutaneous nephrolithotomy (PNL. However, the question of whether PNL or RIRS should be the first-line treatment option for larger stones remains controversial. In this study, we contribute to the debate by comparing the success and complication rates of PNL and RIRS that were used to treat renal pelvis stones 2-3 cm in diameter. Materials and Methods. The medical records of 154 patients (74 PNL, 80 RIRS were retrospectively evaluated. PNL patients were placed in Group 1 and RIRS patients in Group 2. Results. The complete stone-free rates were 95.5% in the PNL group and 80.6% in the RIRS group 1 month postoperatively (P=0.061. The respective complication rates (evaluated using the Clavien system were 13.5% and 8.8% (P=0.520. Conclusions. RIRS affords a comparable success rate, causes fewer complications than PNL, and seems to be a promising alternative to PNL when larger stones are to be treated. Prospective randomized controlled trials are needed to confirm these findings.

  13. SNPs in microRNA binding sites in 3'-UTRs of RAAS genes influence arterial blood pressure and risk of myocardial infarction

    DEFF Research Database (Denmark)

    Nossent, Anne Yaël; Hansen, Jakob Liebe; Doggen, Carine

    2011-01-01

    We hypothesized that single nucleotide polymorphisms (SNPs) located in microRNA (miR) binding sites in genes of the renin angiotensin aldosterone system (RAAS) can influence blood pressure and risk of myocardial infarction.......We hypothesized that single nucleotide polymorphisms (SNPs) located in microRNA (miR) binding sites in genes of the renin angiotensin aldosterone system (RAAS) can influence blood pressure and risk of myocardial infarction....

  14. Reproducibility of intrarenal kinetics of Gd-DOTA with rabbits with dynamic MRI

    International Nuclear Information System (INIS)

    Grenier, N.; Broussin, J.; Barat, J.L.; Ducassou, D.

    1989-01-01

    Ten normal rabbits and seven rabbits with experimental acute renal failure by tubular necrosis were studied with dynamic MR to evaluate the reproducibility of intrarenal kinetics of Gd-DOTA. Sequential spin-echo sequences with short TR (200 msec)/TE (26 msec) were used yielding a 29 sec acquisition time. A usual semi-quantitative analysis of intrarenal contrast demonstrated the reproducilibity of some phases of the dynamic sequence in particular a drop in the signal within inner medulla between the third and the fourth minute after infusion. This effect, related to a high concentration of Gd-DOTA within the tubules was observed in 9 over 10 normal rabbits and in none of the rabbits with acute renal failure. The quantitative analysis calculation was based on relative signal intensity and contrast-to-noise ratio from the absolute signal intensity measure on regions-of-interest (ROI) on the cortex, outer medulla and inner medulla. No reproducibility of the variations with time of these parameters could be assessed. A gread number of factors of variations or error, mainly during the measurements of signal intensity with ROI, could explain this lack of reproducibility. At the present, dynamic MR is therefore not able to quantitatively evaluate the renal function. Only a semi-quantitative estimation of tubular concentration can be deduced [fr

  15. Increased serum erythropoietin activity in rats following intrarenal injection of nickel subsulfide

    International Nuclear Information System (INIS)

    Hopfer, S.M.; Sunderman, F.W. Jr.; Fredrickson, T.N.; Morse, E.E.

    1979-01-01

    To investigate the pathopysiologic mechanisms of nickel-induced erythocytosis, serum erythropoietin activities were measured in (a) pooled serum from rats at 2 wk after intrarenal injection of αNi 3 S 2 (5 mg/rat), and (b) pooled serum from control rats at 2 wk after intrarenal injection of sterile NaCl vehicle (0.4 ml/rat). A sensitive erythropoietin bioassay was employed, which entailed repetitive administration of test serums to post-hypoxic polycythemic mice in divided doses (12 s.c. injections of 0.5 ml of serum at 6 h intervals for 3 da; total dose = 6 ml of serum/mouse). The erythropoietin detection limit was approx. = 20 I.U./liter of serum. In mice which received pooled serum from αNi 3 S 2 -treated rats, erythrocyte 59 Fe-uptake averaged 28% (S.D. +- 5) (vs 3.7 +- 1.1% in control rats; P 3 S 2 -treated rats averaged 130 I.U./liter (S.D. +- 18) (vs 27 +- 6 I.U./liter in control rats; P 3 S 2 is mediated by increased serum erythropoietin activity

  16. An intrarenal abscess as presenting symptom of an infection with Nocardia farcinica in a patient after renal transplantation

    NARCIS (Netherlands)

    van Luin, A.; Manson, W. L.; van der Molen, L.; Homan van der Heide, J. J.; van Son, W. J.

    2008-01-01

    A 52-year-old man presented 8 months after transplantation with an intrarenal mass, which proved to be caused by an infection with Nocardia farcinica. Because of the potential fatal course of nocardiosis, transplantectomy was performed and long-term antibiotic treatment was instituted.

  17. An intrarenal abscess as presenting symptom of an infection with Nocardia farcinica in a patient after renal transplantation

    NARCIS (Netherlands)

    Van Luin, A.; Manson, W. L.; van der Molen, L.; van der Heide, J. J. Homan; van Son, W. J.

    A 52-year-old man presented 8 months after transplantation with an intrarenal mass, which proved to be caused by an infection with Nocardia farcinica. Because of the potential fatal course of nocardiosis, transplantectomy was performed and long-term antibiotic treatment was instituted.

  18. Apparent diffusion coefficient of renal parenchyma and color Doppler ultrasound of intrarenal arteries in patients with cirrhosis related renal dysfunction

    Directory of Open Access Journals (Sweden)

    Mohamed M Hefeda

    2014-12-01

    Conclusion: Liver cirrhosis, even in the presence of refractory ascites, did not affect the ADC value of renal parenchyma, however ADC value is affected in renal parenchyma of patients with hepato-renal syndrome. Duplex-Doppler ultrasound of intrarenal arteries enables the early detection of renal hemodynamic disturbances in patients with liver cirrhosis.

  19. Urinary mitochondrial DNA level is an indicator of intra-renal mitochondrial depletion and renal scarring in diabetic nephropathy.

    Science.gov (United States)

    Wei, Pascal Zhongping; Kwan, Bonnie Ching-Ha; Chow, Kai Ming; Cheng, Phyllis Mei-Shan; Luk, Cathy Choi-Wan; Li, Philip Kam-Tao; Szeto, Cheuk Chun

    2017-12-28

    Mitochondrial dysfunction plays an important role in the pathogenesis and progression of diabetic nephropathy (DN). We study the relation between urinary and intra-renal mitochondrial deoxyribonucleic acid (mtDNA) levels and renal dysfunction in DN. We recruited 92 patients with biopsy-proven DN. Urinary sediment, urinary supernatant and intra-renal mtDNA levels were measured and compared with baseline renal biopsy, kidney scarring and renal function decline in the subsequent 24 months. mtDNA could be detected in all urine supernatant, urine sediment and renal biopsy specimens. There was a modest but statistically significant inverse correlation between urinary supernatant and intra-renal mtDNA levels (r = -0.453, P = 0.012). Urinary supernatant mtDNA level had modest but statistically significant correlations, inversely with estimated glomerular filtration rate (r = -0.214, P = 0.04), and positively with interstitial fibrosis (r = 0.300, P = 0.005). Intra-renal mtDNA had significant inverse correlation with interstitial fibrosis (r = -0.537, P = 0.003). However, there was no significant relation between renal function decline and urinary supernatant, urinary sediment or intra-renal mtDNA levels. mtDNA is readily detectable in urinary supernatant and kidney tissue, and their levels correlate with renal function and scarring in DN. Further studies are needed to determine the accuracy of urinary supernatant mtDNA level as a prognostic indicator of DN, as well as its role in other kidney diseases. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  20. The role of urocortins in the cardiovascular system.

    Science.gov (United States)

    Walczewska, J; Dzieza-Grudnik, A; Siga, O; Grodzicki, T

    2014-12-01

    Urocortins (Ucn) 1, 2 and 3 are a group of endogenous peptide hormones belonging to the corticotropin-releasing hormone (CRH) family of peptides. The presence of urocortins has been detected in the central nervous system as well as in peripheral tissues. They play an important role in a stress response (with respect to its duration, intensity and restoration of homeostasis). They also act as regulatory factors of the cardiovascular, gastrointestinal, reproductive and immune systems. Urocortins act by binding to G-protein-coupled receptors (GPCR). The "central" effects of urocortins are mediated mainly by activation of CRH receptor 1 (CRH-R1), and the "peripheral" effects by activation of CRH-R2. Ucn2 and Ucn3 are selective CRH-R2 agonists and have much higher binding affinity to this receptor than CRH and Ucn1. Recent studies have shown that urocortins exert various biological effects in the cardiovascular system, such as vasodilation, positive inotropic and lusitropic effects, as well as cardioprotection against ischemia-reperfusion injury. They also suppress the renin-angiotensin system and may have an impact on the sympathetic nervous system. Urocortins and CRH-R2 may be a potential therapeutic target in coronary heart disease, congestive heart failure and hypertension. This review summarizes the data published to date on the role of urocortins in the cardiovascular system.

  1. Nutritional status and intrarenal arterial stiffness in cardiorenal syndrome: a pilot study.

    Science.gov (United States)

    Gigante, A; Di Mario, F; Barbano, B; Rosato, E; Di Lazzaro Giraldi, G; Pofi, R; Gasperini, M L; Amoroso, D; Cianci, R; Laviano, A

    2017-01-01

    Cardio-Renal Syndrome (CRS) is a condition, which is more frequently observed in clinical practice. The aim of this study is to explore nutritional status and intrarenal arterial stiffness in patients affected by CRS. 14 consecutive CRS patients, screened for anthropometry, biochemistry, nutritional and metabolic status underwent renal Doppler ultrasound and whole-body bioimpedance spectroscopy (BIS). We found a positive correlation between phase angle (PA) and CKD-EPI and MDRD (p=0.011 and p=0.007), and between body mass index and renal resistive index (RRI) (p=0.002). Finally, we found a negative correlation between fat-free mass and RRI (p=0.024). Body composition assessment may improve the care of patients with chronic kidney disease (CKD). Also, BIS may help identify changes in hydration status in CKD patients resulting as a significant predictor of mortality.

  2. Retrograde intrarenal stone surgery for extracorporeal shock-wave lithotripsy-resistant kidney stones

    DEFF Research Database (Denmark)

    Jung, Helene; Nørby, Bettina; Osther, Palle Jörn

    2006-01-01

    OBJECTIVE: The newer flexible ureteroscopes, 150-200-microm holmium YAG laser fibres and superflexible Dormia baskets have made it possible to reach and treat stones in all parts of the kidney. The object of this evaluation was to study the outcome of retrograde intrarenal stone surgery (RIRS......) for extracorporeal shock-wave lithotripsy (ESWL)-resistant kidney stones. MATERIAL AND METHODS: A total of 38 consecutive patients (18 males, 20 females) participated in the study. All patients had undergone ESWL prior to RIRS without success. In all cases the stones could be reached with the endoscope. Calculi...... ranged in size from 3 to 20 mm (mean 9 mm). In 32 cases the stones were fragmented using a holmium YAG laser and in six the stones could be extracted using zero-tip Dormia baskets without fragmentation. Sixteen patients had lower calyceal calculi and eight had an abnormal anatomy of the upper urinary...

  3. Current status of retrograde intrarenal surgery for management of nephrolithiasis in children

    Directory of Open Access Journals (Sweden)

    Yaser El-Hout

    2010-01-01

    Full Text Available Purpose : To review the current status of retrograde intrarenal surgery (RIRS for renal stones in children focusing on its indications, outcomes and success in the management of nephrolithiasis. Materials and Methods : Between 1988 and 2009, a comprehensive PubMed/MEDLINE literature review on RIRS was conducted. Results : The available literature is limited and heterogeneous, skewed by favorable results on ureteral stone outcomes. However, recent case series report outcomes comparable to time-honored modalities: percutaneous nephrolithotomy and shock wave lithotripsy. Concerns about urinary tract damage are not substantiated by the yet available intermediate-term follow-up. Conclusions : RIRS seems to be an effective modality in pediatric nephrolithiasis management. However, long-term outcomes and comparative prospective randomized studies are awaited.

  4. The value of intrarenal resistive index in patients with liver cirrhosis

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    Lee, Young Rae [Kangbuk Samsung Hospital, Seoul (Korea, Republic of)

    1997-08-01

    To determine whether the value of the intrarenal resistive index(RI) can be used to identify early kidney vasoconstriciton in patients with nonazotemic liver cirrhosis The intrarneal resistive index (RI), kidney and liver function and plasma renin activity were measured in 12 healthy control subjects, 13 cirrhotic patients without ascites and 29 cirrhotic patients with ascites. To evaluate the development of hepatorenal syndrome, patients were followed up for six months. RI was significantly higher in patients with cirrhosis (0.68{+-}0.06) than in healthy subjects (0.59{+-}0.04). In 42 cirrhotic patients, it was significantly higher in those with ascites (0.69{+-}0.05) than in those without ascites (0.64{+-}0.05) and correlated with creatinine clearance. Plasma renin activity was significantly highter in cirrhotic patients with ascites than in those without ascites and healthy subjects (p<0.05). During the six-month follow-up period, kidney dysfunction developed in 16%(7/42) of cirrhotic patiens, and in 37%(6/16) of those with an elevated RI. In contrast, only 4%(1/26) of patients with a normal RI has kidney dysfunction. The measurement of intrarenal resitive index(RI) using duplex Doppler ultrasound is a simple, noninvasive method of detecting even subtle derangements of renal hemodynamics in liver cirrhosis patients;the procedure can be used to identify those who are at higher risk of overt renal failure and to help decide whether a therapeutic approach involving paracentesis, diuretics, or nephrotoxic agents is most appropriate.

  5. Bilateral Single-Session Retrograde Intrarenal Surgery for the Treatment of Bilateral Renal Stones

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    Gokhan Atis

    2013-06-01

    Full Text Available Purpose The aim of the study was to evaluate the efficacy and safety of bilateral single-session retrograde intrarenal surgery in the treatment of bilateral renal stones. Materials and Methods From December 2008 to February 2012, 42 patients who had undergone bilateral single-session retrograde intrarenal surgery (RIRS and laser lithotripsy were included in the study. The procedures were performed in the lithotomy position on an endoscopy table under general anesthesia, beginning on the side in which the stone size was smaller. Plain abdominal radiography, intravenous urograms (IVU, renal ultrasonography (USG and / or non-contrast tomography (CT scans were conducted for all patients. The success rate was defined as patients who were stone-free or only had residual fragment less than 4 mm. Results A total of 42 patients (28 male, 14 female with a mean age 39.2 ± 14.2 were included in the present study. The mean stone size was 24.09 ± 6.37 mm with a mean operative time of 51.08 ± 15.22 minutes. The stone-free rates (SFR were 92.8% and 97.6% after the first and second procedures, respectively. The average hospital stay was 1.37 ± 0.72 days. In two patients (4.7%, minor complications (Clavien I or II were observed, whereas no major complications (Clavien III-V or blood transfusions were noted in the studied group. Conclusions Bilateral single-session RIRS and laser lithotripsy can be performed safely and effectively with a high success rate and low complication rate in patients with bilateral renal stones.

  6. Autonomic nervous system involvement in pulmonary arterial hypertension.

    Science.gov (United States)

    Vaillancourt, Mylène; Chia, Pamela; Sarji, Shervin; Nguyen, Jason; Hoftman, Nir; Ruffenach, Gregoire; Eghbali, Mansoureh; Mahajan, Aman; Umar, Soban

    2017-12-04

    Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disease characterized by increased pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Autonomic nervous system involvement in the pathogenesis of PAH has been demonstrated several years ago, however the extent of this involvement is not fully understood. PAH is associated with increased sympathetic nervous system (SNS) activation, decreased heart rate variability, and presence of cardiac arrhythmias. There is also evidence for increased renin-angiotensin-aldosterone system (RAAS) activation in PAH patients associated with clinical worsening. Reduction of neurohormonal activation could be an effective therapeutic strategy for PAH. Although therapies targeting adrenergic receptors or RAAS signaling pathways have been shown to reverse cardiac remodeling and improve outcomes in experimental pulmonary hypertension (PH)-models, the effectiveness and safety of such treatments in clinical settings have been uncertain. Recently, novel direct methods such as cervical ganglion block, pulmonary artery denervation (PADN), and renal denervation have been employed to attenuate SNS activation in PAH. In this review, we intend to summarize the multiple aspects of autonomic nervous system involvement in PAH and overview the different pharmacological and invasive strategies used to target autonomic nervous system for the treatment of PAH.

  7. Primary hyperparathyroidism and the cardiovascular system.

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    Kiernan, Thomas J; O'Flynn, Anne Marie; McDermott, John H; Kearney, Peter

    2006-11-18

    The role of primary hyperparathyroidism (PHPT) in heart disease is still somewhat uncertain in many respects. Patients with PHPT seem to have an increase in mortality and this seems mainly due to an overrepresentation of cardiovascular death. PHPT is reported to be associated with hypertension, disturbances in the renin-angiotensin-aldosterone system, cardiac arrhythmias as well as structural and functional alterations in the vascular wall. There is an increased prevalence of cardiac structural abnormalities such as LVH and functional properties of the heart may be affected by the hyperparathyroid condition as well. We report the case of a 65-year-old woman with no cardiac risk factors apart from her age and type 2 diabetes who presented in cardiogenic shock. Extensive evaluation for the aetiology of the cardiomyopathy revealed solely a diagnosis of primary hyperparathyroidism. Cardiac manifestations of primary hyperparathyroidism have been reported before but to our knowledge this is the first description of severe left ventricular function secondary to PHPT. We believe that this atypical presentation of primary hyperparathyroidism causing left ventricular cardiomyopathy warrants further attention, and that a diagnosis of primary hyperparathyroidism should always be considered in patients with systolic as well as diastolic left ventricular dysfunction, and no other obvious cause.

  8. Study of intrarenal vasculature in cases of primary and secondary hypertension (by metallic impregnation technique on whole kidney section

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    Mittal B

    1992-10-01

    Full Text Available Study of intrarenal vasculature was carried out by using the metallic impregnation technique on whole kidney sections in 31 [corrected] cases of (primary and secondary hypertension and 10 normal controls. Distinct patterns of intrarenal vasculature were noted in controls and in cases of hypertension. Gradual tapering of vessels, absence of tortuosity and good peripheral vascularisation were noted in controls. Abrupt tapering, tortuosity of vessels and poor peripheral vascularisation were noted in hypertensive cases. In essential hypertension moderate to severe changes of dilatation of the segmental and/or arcuate arteries was noted. The degree of dilatation was related to the level of systolic BP rather than diastolic in cases of essential hypertension. Secondary hypertension even if severe, rarely showed significant dilatation lesions. Avascular zones and conglomeration of vessels at poles was seen only in cases of pyelonephritis. This helped in distinguishing these, from cases of glomerulonephritis.

  9. Distribution of renal scars and intrarenal reflux in children with a past history of urinary tract infection

    International Nuclear Information System (INIS)

    Hannerz, L.; Wikstad, I.; Johansson, L.; Broberger, O.; Aperia, A.

    1987-01-01

    The distribution of renal scars in children with vesicoureteral reflux (VUR) and a past history of urinary tract infection was studied to see whether a correlation existed between renal scaring and intrarenal reflux. In 37 children with one or more scars in one or both kidneys, scarring was significantly more frequent in the polar areas than in the lateral area. In 7 children with intrarenal reflux (IRR), the distribution of IRR was almost identical with that of renal scarring. When children with marked VUR (grade IV-V) were analyzed separately, a uniform distribution of scars was found. It was concluded that fused papillae, which normally are most frequent in the polar area, are a prerequisite for the development of IRR/renal scars. (orig.)

  10. Alternative pathways for angiotensin II generation in the cardiovascular system

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    C. Becari

    2011-09-01

    Full Text Available The classical renin-angiotensin system (RAS consists of enzymes and peptides that regulate blood pressure and electrolyte and fluid homeostasis. Angiotensin II (Ang II is one of the most important and extensively studied components of the RAS. The beneficial effects of angiotensin converting enzyme (ACE inhibitors in the treatment of hypertension and heart failure, among other diseases, are well known. However, it has been reported that patients chronically treated with effective doses of these inhibitors do not show suppression of Ang II formation, suggesting the involvement of pathways alternative to ACE in the generation of Ang II. Moreover, the finding that the concentration of Ang II is preserved in the kidney, heart and lungs of mice with an ACE deletion indicates the important role of alternative pathways under basal conditions to maintain the levels of Ang II. Our group has characterized the serine protease elastase-2 as an alternative pathway for Ang II generation from Ang I in rats. A role for elastase-2 in the cardiovascular system was suggested by studies performed in heart and conductance and resistance vessels of normotensive and spontaneously hypertensive rats. This mini-review will highlight the pharmacological aspects of the RAS, emphasizing the role of elastase-2, an alternative pathway for Ang II generation.

  11. GENDER DISTINCTIONS OF MICROALBUMINURIA AND ITS RELATION TO INTRARENAL HEMODYNAMIC AND LEPTIN LEVEL IN ARTERIAL HYPERTENSION

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    V. I. Podzolkov

    2012-01-01

    Full Text Available Aim. To assess an incidence of microalbuminuria (MAU depending on gender and its relation to intrarenal hemodynamic, glomerular filtration rate (GFR, and leptin serum level in essential hypertension (HT. Material and methods. 149 patients (61 men and 88 women, aged 49.4±7.1 years, body mass index 32.2±3.8 kg/m2 with HT degree 2-3 were examined. Clinical characteristics in men and women were comparable. Ultrasonography of intrarenal vessels was performed in all patients. GFR was calculated by isotope nephroangioscintigraphy. Leptin serum level was determined\\ by radioimmunoassay. MAU was detected by semiquantitative test. Results were processed with SPSS-11.0 software package. Results. MAU incidence was higher among female hypertensives in contrast to males: 40% vs 26% (p=0.056. Hypertensives with MAU of both genders demonstrated higher both resistance index (RI and pulsatility index (PI. Gender differences of both RI and PI in patients with MAU were highly significant (p<0.001 at all levels of arterial visualization (renal, segmental and interlobar. Female hypertensives with MAU had lower GFR (79.1±13.2 ml/min/1.73m2 than those without MAU (89.3±17.2 ml/min/1.73m2. Male hypertensives with MAU had higher GFR than those without MAU: 126±32.5 vs 105.4±16.7 ml/min/1.73m2, respectively. Serum leptin level in females with MAU was higher than this in female patients without MAU: 103.5±38.7 vs 76.7±46.4 ng/ml (p=0.04, respectively. Leptin levels did not differ in males with or without MAU. In males MAU positively correlated with GFR (r=0.372, р=0.003, where-as in females – correlation was negative (r=-0.34, р=0.02. Besides, in females MAU correlated with serum leptin level (r=0.48, p=0.01 Conclusion. Female hypertensives with MAU demonstrate more stable elevation of RI and PI in contrast to hypertensive males with MAU. MAU level correlates with GFR in opposite ways: in males positively whereas in females — negatively.

  12. Obstructive Sleep Apnea Syndrome (OSAS) and Cardiovascular System.

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    Lombardi, Carolina; Tobaldini, Eleonora; Montano, Nicola; Losurdo, Anna; Parati, Gianfranco

    2017-08-28

    There is increasing evidence of a relationship between Obstructive Sleep Apnea (OSA) and cardiovascular diseases. The strong association between OSA and arterial hypertension, in particular in patients with resistant hypertension and/or a non-dipping profile, has been extensively reported. The relationship between OSA and high blood pressure (BP) has been found independent from a number of confounders, but several factors may affect this relationship, including age and sex. It is thus important to better assess pathophysiologic and clinical interactions between OSA and arterial hypertension, also aimed at optimizing treatment approaches in OSA and hypertensive patients with co-morbidities. Among possible mechanisms, cardiovascular autonomic control alterations, altered mechanics of ventilation, inflammation, endothelial dysfunction, and renin-angiotensin-aldosterone system should be considered with particular attention. Additionally, available studies also support the occurrence of a bidirectional association between OSA and cardiovascular alterations, in particular heart failure, stroke and cardiac arrhythmias, emphasizing that greater attention is needed to both identify and treat sleep apneas in patients with cardiovascular diseases. However, a number of aspects of such a relationship are still to be clarified, in particular with regard to gender differences, effect of sleep-related breathing disorders in childhood, and influence of OSA treatment on cardiovascular risk, and they may represent important targets for future studies.

  13. Increased urinary Angiotensinogen/Creatinine (AGT/Cr) ratio may be associated with reduced renal function in autosomal dominant polycystic kidney disease patients.

    Science.gov (United States)

    Park, Hayne Cho; Kang, Ah-Young; Jang, Joon Young; Kim, Hyunsuk; Han, Miyeun; Oh, Kook-Hwan; Kim, Seung Hyup; Noh, Jung Woo; Cheong, Hae Il; Hwang, Young-Hwan; Ahn, Curie

    2015-06-20

    Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary kidney diseases that frequently result in renal failure. In this cross-sectional observational cohort study, we evaluated urinary angiotensinogen (AGT) as a potential biomarker to assess renal function in ADPKD. Urinary AGT was measured in 233 ADPKD patients and its association with estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume (htTKV) were evaluated. The localization of AGT and other renin-angiotensin system (RAS)-related molecules were identified using immunohistochemistry in human ADPKD tissues. Baseline urinary AGT/Cr was negatively correlated with CKD-EPI eGFR (r(2) = 0.162, P urinary AGT/Cr and plasma renin activity levels were significantly elevated in hypertensive ADPKD patients. Among hypertensive subjects, urinary AGT/Cr was significantly increased in the advanced CKD stages (III-V) compared to early CKD stages (I-II) (28.6 ± 60.3 vs. 93.2 ± 139.3 μg/g, P lining epithelial cells as well as the nearby compressed tubular epithelial cells. Our results suggested that urinary AGT/Cr may be a valuable biomarker for renal damage in ADPKD since intrarenal ischemic insults induced by cyst growth and subsequent intrarenal RAS activation may play a potential role in the development of hypertension and renal dysfunction in ADPKD.

  14. Diagnosis of intrarenal reflux and its role in pathogenesis of reflux nephropathy in children

    Energy Technology Data Exchange (ETDEWEB)

    Fujimatsu, Akiko [Kurume Univ., Fukuoka (Japan). School of Medicine

    2000-06-01

    We compared newly developed radionuclide cystography with conventional contrast voiding cystography (VCG) with regard to their diagnostic usefulness of intrarenal reflux (IRR) in children. Based on the imaging findings, we assessed the role of IRR in the pathogenesis of reflux nephropathy (RN). Among the ureters which revealed IRR diagnosed by radionuclide cystography, 38.9% (7 out of 18 ureters) of the cases examined by VCG had IRR. In the case of VCG, the sensitivity and specificity of IRR detection were 33.3% and 100%, respectively. There was a statistical correlation between the presence/absence of IRR and vesicoureteral reflux (VUR). RN was significantly correlated with advanced grade of VUR associated with IRR. Among 9 kidneys of the subjects who had suffered from urinary tract infection (UTI) only once, IRR was detected in 33.3% (3/9) and RN in 66.7% (2/3). From these findings, conventional contrast VCG is considered not effective for the diagnosis of IRR. Moreover, it is suggested that VUR complicated with IRR is deeply associated with the development of RN. In addition, it is suggested that UTI might be related to the onset of IRR. (author)

  15. Evaluation of the effect of Retrograde Intrarenal Surgery with Myo-Inositol Oxygenase

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    Mertoglu, Cuma; Bozkurt, Aliseydi; Keskin, Ercüment; Gunay, Murat

    2018-01-01

    Objective: To investigate the effect of retrograde intra-renal surgery (RIRS) on kidneys using the myo-inositol oxygenase (MIOX) enzyme. MIOX is a renal tubular-specific novel marker for the early diagnosis of acute kidney injury. Methods: A total of twenty seven individuals that had undergone RIRS to treat kidney stones were included in the study. Biochemical tests were performed on serum samples collected immediately before RIRS (hour 0) and at the 6th and 24th hours after the surgery. Results: The creatinine value at hour 6 was lower than the baseline (hour 0) value (p = 0.0305). Cystatin C at hour 6 was lower than the value measured at hour 24 (p = 0.0142). Similarly, MIOX was lower at hour 6 compared to hour 24 (p = 0.0214). MIOX/creatinine at hour 6 was lower than the value calculated at hour 24 (p = 0.0348). The basal values of MIOX and creatinine were found to have a positive correlation (correlation coefficient r = 0.5946, p = 0.0035). Conclusions: Similar to the serum creatinine, the serum MIOX level provides information about kidney functions. RIRS was confirmed to be a safe procedure for the treatment of acute kidney injury with no negative effects on the kidneys. PMID:29643901

  16. Retrograde intrarenal surgery (RIRS) in the treatment of calyceal diverticulum with lithiasis.

    Science.gov (United States)

    Palmero, Jose Luis; Miralles, Jaume; Garau, Carmen; Nuño de la Rosa, Ines; Amoros, Araceli; Benedicto, Antonio

    2014-05-01

    To evaluate the result of retrograde intrarenal surgery (RIRS) assisted by flexible ureterorenoscopy (FURS) and Holmium laser in the treatment of lithiasis within calyceal diverticula as a minimally invasive therapeutic option. We retrospectively evaluated 11 cases of symptomatic lithiasis within calyceal diverticula treated between January 2010 and December 2011. We defined treatment success as absence of residual stones and absence/disappearance of symptomatology over the course of follow-up. We describe the RIRS technique and maneuvers for locating the diverticulum, opening the neck, and fragmenting intradiverticular lithiasis. The most frequently experienced symptom was flank pain (72.7%). The size of the lithiasis treated ranged from 7-20 mm. The overall success rate of RIRS was approximately 73% (absence of lithiasis and disappearance of symptoms) with an average follow-up of 13.3 months. Three cases were not solved by RIRS (2 due to unsuccessful location of the neck, 1 due to persistence of lithiasis and symptoms) . Cases of unsuccessful location were treated with laparoscopic surgery. RIRS assisted by FURS and Holmium laser is an effective and minimally invasive procedure for the treatment of lithiasis in the interior of the calyceal diverticulum. This treatment's efficacy improves upon the results from ESWL (extracorporeal shock wave lithotripsy( and equals that of the percutaneous method, exhibiting a lower rate of complications.

  17. ADAMTS13 Retards Progression of Diabetic Nephropathy by Inhibiting Intrarenal Thrombosis in Mice.

    Science.gov (United States)

    Dhanesha, Nirav; Doddapattar, Prakash; Chorawala, Mehul R; Nayak, Manasa K; Kokame, Koichi; Staber, Janice M; Lentz, Steven R; Chauhan, Anil K

    2017-07-01

    ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I repeats-13) prevents microvascular thrombosis by cleaving prothrombogenic ultralarge von Willebrand factor (VWF) multimers. Clinical studies have found association between reduced ADAMTS13-specific activity, ultralarge VWF multimers, and thrombotic angiopathy in patients with diabetic nephropathy. It remains unknown, however, whether ADAMTS13 deficiency or ultralarge VWF multimers have a causative effect in diabetic nephropathy. The extent of renal injury was evaluated in wild-type (WT), Adamts 13 -/- and Adamts 13 -/- Vwf -/- mice after 26 weeks of streptozotocin-induced diabetic nephropathy. We found that WT diabetic mice exhibited low plasma ADAMTS13-specific activity and increased VWF levels ( P thrombosis (assessed by plasminogen activator inhibitor, VWF, fibrin(ogen), and CD41-positive microthrombi), increased mesangial cell expansion, and extracellular matrix deposition ( P thrombosis, and alleviated histological changes in glomeruli, suggesting that exacerbation of diabetic nephropathy in the setting of ADAMTS13 deficiency is VWF dependent. ADAMTS13 retards progression of diabetic nephropathy, most likely by inhibiting VWF-dependent intrarenal thrombosis. Alteration in ADAMTS13-VWF balance may be one of the key pathophysiological mechanisms of thrombotic angiopathy in diabetes mellitus. © 2017 American Heart Association, Inc.

  18. Association of Serum CXCL13 with Intrarenal Ectopic Lymphoid Tissue Formation in Lupus Nephritis

    Science.gov (United States)

    Chen, Wen Li; Long, Kang Xia; Zhang, Xiao

    2016-01-01

    Aims. To assess the concentrations of serum CXCL13 and intrarenal ectopic lymphoid tissue (ELT) profiles and their correlation in the patients with lupus nephritis (LN). Methods. Serum CXCL13 levels were measured using enzyme-linked immunosorbent assays (ELISA). The expression of CD3, CD20, and CD21 in renal biopsy specimens was tested using immunohistochemical methods. Results. Serum CXCL13 levels were significantly higher in the LN group than those in the SLE group without LN and also in the type III and IV LN patients than in type V LN patients. LN patients with positive CD20 expression (CD20+ LN) had a longer disease course and poorer response to combination therapy and higher serum CXCL13 levels than CD20− LN patients. Moreover, the serum CXCL13 level was positively correlated with the number of B cells/HP in the renal tissue of LN patients. The coexpression patterns of CD3, CD20, and CD21 in the renal tissue of LN patients with different WHO pathological types were significantly different. Serum CXCL13 levels were significantly higher in ELT-2 type LN patients than in 0 or 1 type LN patients. Conclusions. This study suggested that increased serum levels of CXCL13 might be involved in renal ELT formation and renal impairment process in LN. PMID:27990444

  19. Association of Serum CXCL13 with Intrarenal Ectopic Lymphoid Tissue Formation in Lupus Nephritis

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    De Ning He

    2016-01-01

    Full Text Available Aims. To assess the concentrations of serum CXCL13 and intrarenal ectopic lymphoid tissue (ELT profiles and their correlation in the patients with lupus nephritis (LN. Methods. Serum CXCL13 levels were measured using enzyme-linked immunosorbent assays (ELISA. The expression of CD3, CD20, and CD21 in renal biopsy specimens was tested using immunohistochemical methods. Results. Serum CXCL13 levels were significantly higher in the LN group than those in the SLE group without LN and also in the type III and IV LN patients than in type V LN patients. LN patients with positive CD20 expression (CD20+ LN had a longer disease course and poorer response to combination therapy and higher serum CXCL13 levels than CD20− LN patients. Moreover, the serum CXCL13 level was positively correlated with the number of B cells/HP in the renal tissue of LN patients. The coexpression patterns of CD3, CD20, and CD21 in the renal tissue of LN patients with different WHO pathological types were significantly different. Serum CXCL13 levels were significantly higher in ELT-2 type LN patients than in 0 or 1 type LN patients. Conclusions. This study suggested that increased serum levels of CXCL13 might be involved in renal ELT formation and renal impairment process in LN.

  20. Basic studies on intrarenal localization of renal scanning agent sup(99m)Tc-DMSA

    International Nuclear Information System (INIS)

    Hosokawa, Shinichi; Kawamura, Juichi; Yoshida, Osamu

    1978-01-01

    An experimental study was carried out on sup(99m)Tc-dimercaptosuccinic acid (sup(99m)Tc-DMSA) uptake and intrarenal localization using Wistar rats. Total renal uptake was 50.27% 2 hours after injection of DMSA. The uptake per one gram kidney weight was 23.89% in average on both kidneys. If the uptake of one kidney is called 100%, the renal cortical uptake was 95.72%, whereas the renal medullary uptake was 4.27%. Macroautoradiography showed that most of DMSA is localized in the renal cortex. The renal cortex was separated into the glomerulus and the tubulo-interstitial tissue by Spiro's method. The glomerular uptake was 3.6% and the tubulo-interstitial uptake was 96.4%. Thus, DMSA uptake of the kidneys measured outside of the body reflects the actual renal uptake of this substance. It was again confirmed that DMSA accumulates to the renal cortex and presents renal cortical function well. Our renal uptake formula of DMSA was proved to be correct both in the experimental and clinical studies. It would be useful for the clinical kidney function studies. (auth.)

  1. Regulation of the renin–angiotensin system in coronary atherosclerosis: A review of the literature

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    Ramadan A Hammoud

    2008-01-01

    Full Text Available Ramadan A Hammoud, Christopher S Vaccari, Sameer H Nagamia, Bobby V KhanEmory University School of Medicine, Division of Cardiology, Grady Memorial Hospital Vascular Research Laboratory, Atlanta, Georgia, USAAbstract: Activation of the renin–angiotensin system (RAS is significant in the pathogenesis of cardiovascular disease and specifically coronary atherosclerosis. There is strong evidence that the RAS has effects on the mechanisms of action of atherosclerosis, including fibrinolytic balance, endothelial function, and plaque stability. Pharmacological inhibition of the renin angiotensin system includes angiotensin converting enzyme (ACE inhibitors, angiotensin receptor blockers (ARBs, and renin inhibitors. These agents have clinical benefits in reducing morbidity and mortality in the management of hypertension. In addition, ACE inhibitors and ARBs have shown to be effective in the management of congestive heart failure and acute myocardial infarction. This review article discusses the biochemical and molecular mechanisms involving the RAS in coronary atherosclerosis as well as the effects of RAS inhibition in clinical studies involving coronary atherosclerosis.Keywords: angiotensin II, atherosclerosis, endothelium, inflammation, vasculature

  2. Redox modification of caveolar proteins in the cardiovascular system- role in cellular signalling and disease.

    Science.gov (United States)

    Bubb, Kristen J; Birgisdottir, Asa Birna; Tang, Owen; Hansen, Thomas; Figtree, Gemma A

    2017-08-01

    Rapid and coordinated release of a variety of reactive oxygen species (ROS) such as superoxide (O 2 .- ), hydrogen peroxide (H 2 O 2 ) and peroxynitrite, in specific microdomains, play a crucial role in cell signalling in the cardiovascular system. These reactions are mediated by reversible and functional modifications of a wide variety of key proteins. Dysregulation of this oxidative signalling occurs in almost all forms of cardiovascular disease (CVD), including at the very early phases. Despite the heavily publicized failure of "antioxidants" to improve CVD progression, pharmacotherapies such as those targeting the renin-angiotensin system, or statins, exert at least part of their large clinical benefit via modulating cellular redox signalling. Over 250 proteins, including receptors, ion channels and pumps, and signalling proteins are found in the caveolae. An increasing proportion of these are being recognized as redox regulated-proteins, that reside in the immediate vicinity of the two major cellular sources of ROS, nicotinamide adenine dinucleotide phosphate oxidase (Nox) and uncoupled endothelial nitric oxide synthase (eNOS). This review focuses on what is known about redox signalling within the caveolae, as well as endogenous protective mechanisms utilized by the cell, and new approaches to targeting dysregulated redox signalling in the caveolae as a therapeutic strategy in CVD. Copyright © 2017. Published by Elsevier Inc.

  3. Protective Role of Mast Cells in Primary Systemic Vasculitis: A Perspective

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    Jason M. Springer

    2017-08-01

    Full Text Available Mast cells are important cells of the immune system. Although traditionally considered as key players in allergic and hypersensitivity reactions, emerging evidence suggests that mast cells have many complex roles in vascular disease. These include regulation of vasodilation, angiogenesis, activation of matrix metalloproteinases, apoptosis of smooth muscle cells, and activation of the renin angiotensin system. Mast cells are also known to play an immunomodulatory role via modulation of regulatory T-cell (Treg, macrophage and endothelial cell functions. This dual role of the mast cells is evident in myeloperoxidase anti-neutrophil cytoplasmic antibodies-mouse model of glomerulonephritis in which mast cell deficiency worsens glomerulonephritis, whereas inhibition of mast cell degranulation is effective in abrogating the development of glomerulonephritis. Our previous work demonstrated that mast cell degranulation inhibits lipopolysaccharide-induced interleukin 6 (IL-6 production in mice. This effect was not seen in histamine-1-receptor knockout (H1R−/− mice suggesting a role for histamine in IL-6 homeostasis. In addition, mast cell degranulation-mediated decrease in IL-6 production was associated with an upregulation of suppressor of cytokine signaling-1 protein in the aorta. We propose that mast cells regulate large artery inflammation through T-cells, shifting a primarily Th1 and Th17 toward a Th2 response and leading to enhanced IL-10 production, activation Treg cells, and the inhibition of macrophage functions.

  4. Once and for all, LXRα and LXRβ are gatekeepers of the endocrine system.

    Science.gov (United States)

    Maqdasy, Salwan; Trousson, Amalia; Tauveron, Igor; Volle, David H; Baron, Silvère; Lobaccaro, Jean-Marc A

    2016-06-01

    Liver X receptors (LXRs) α and β are nuclear receptors whose transcriptional activity is regulated by oxysterols, the oxidized forms of cholesterol. Described in the late 1990s as lipid sensors, both LXRs regulate cholesterol and fatty acid homeostasis. Over the years, deep phenotypic analyses of mouse models deficient for LXRα and/or LXRβ have pointed out various other physiological functions including glucose homeostasis, immunology, and neuroprotection. This review enlightens the "endocrine" functions of LXRs; they deeply impact plasma glucose directly and by modulating insulin signaling, renin-angiotensin-aldosterone axis, thyroid and pituitary hormone levels, and bone homeostasis. Besides, LXR signaling is also involved in adrenal physiology, steroid synthesis, and male and female reproduction. Hence, LXRs are definitely involved in the endocrine system and could thus be considered as endocrine receptors, even though oxysterols do not fully correspond to the definition of hormones. Finally, because they are ligand-regulated transcription factors, LXRs are potential pharmacological targets with promising beneficial metabolic effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. New intrarenal echo-Doppler velocimetric indices for the diagnosis of renal artery stenosis.

    Science.gov (United States)

    Bardelli, M; Veglio, F; Arosio, E; Cataliotti, A; Valvo, E; Morganti, A

    2006-02-01

    We aimed at comparing the positive and negative predictive values (PPV, NPV) of several intrarenal velocimetric indices for revealing the presence of renal artery stenosis (RAS) among hypertensive patients who underwent a renal angiography for the clinical suspicion of renovascular hypertension. In 106 patients (200 kidneys), the pulsatility index (PI) and resistive index (RI), the acceleration time (AT), and the mean systolic acceleration (ACC(sys)) were evaluated. In addition, the maximal systolic acceleration (ACC(max)), that is, the maximal slope of the acceleration phase, and the maximal acceleration index (AI(max)), that is, the ratio between ACC(max) and the relative peak systolic velocity, were calculated. On angiography, we found that 56 (28%) of the 200 arteries had a greater than 60% RAS. PI and RI had an NPV below 75%, whereas AT, ACC(sys), ACC(max), and AI(max) had an NPV always above 95%. However, ACC(max), and AI(max), at their best cutoff limits, had higher PPV than ACC(sys) and AT (60 and 70% vs 45 and 51%, respectively). Thus, in a cohort of patients with a high prevalence of RAS, PI and RI failed to reach an NPV adequate for a screening test. In contrast, all the acceleration indices we tested had a sufficiently high NPV but AI(max) appears superior to the others because of higher PPV. We propose the evaluation of AI(max) as an additional screening test in patients with hypertension and the clinical suspicion of RAS.

  6. Retrograde intrarenal surgery with holmium-YAG laser lithotripsy in the primary treatment of renal lithiasis.

    Science.gov (United States)

    Redondo, C; Ramón de Fata, F; Gimbernat, H; Meilán, E; Andrés, G; Angulo, J C

    2015-06-01

    retrograde intrarenal surgery (RIRS) appears as a safe and effective technique as well as a good therapeutic alternative to extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PNL). descriptive study in 50 patients surgically treated between November 2012 and April 2013. Demographic, operative and postoperative data as well as early and late complications data were collected. The minimum follow-up of patients was one year. Surgery was performed under general anesthesia. Flexible ureteroscopy with ureteral access sheath and laser fragmentation were employed. Surgery success was defined as stone free rate in postoperative control test and at three months after surgery (simple radiography, abdominal ultrasound or CT without contrast). mean age was 51.1±15.5 years old. The highest-frequency location was the lower calyceal group (26%), single stones were described in 58% of patients whilst multiple lithiasis were found in the 42%. Regarding the stone burden in 44% of the patients was low (3 cm) in 22% of the patients. The stone clearance rate was 89.7±17.5. Average surgery time was 96.6±35.2min. Complications were reported in 4 patients (8%), all of them early ones and minor in nature. RIRS is an effective and safe option whose results are comparable to ESWL and PCNL. RIRS can be considered as first-line treatment. These results are corroborated by numerous studies. To strengthen these findings, prospective studies focusing on quality of life, length of stay, complications and cost-effectiveness of different treatments are needed. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Comparison of Retrograde Intrarenal Surgery and Micro-Percutaneous Nephrolithotomy in Moderately Sized Pediatric Kidney Stones.

    Science.gov (United States)

    Baş, Okan; Dede, Onur; Aydogmus, Yasin; Utangaç, Mazhar; Yikilmaz, Taha Numan; Damar, Erman; Nalbant, İsmail; Bozkurt, Ömer Faruk

    2016-07-01

    To compare the effectiveness and reliability of retrograde intrarenal surgery (RIRS) and micro-percutaneous nephrolithotomy (micro-perc) for the management of kidney stones in pediatric patients. A retrospective analysis was made of pediatric patients aged kidney stones that ranged from 10 to 20 mm in size, who underwent RIRS (n = 36) or micro-perc (n = 45) in referral centers. In the RIRS group, the mean age of patients was 8.39 ± 4.72 years and in the micro-perc group, it was 5.62 ± 4.50 years (p = 0.01). The mean stone size was 12.80 ± 3.03 mm in the RIRS group and 13.97 ± 3.46 mm in the micro-perc group (p = 0.189). The success rate was 86.2% (n = 31) in the RIRS group and 80.0% (n = 36) in the micro-perc group (p = 0.47). The mean complication rate was 16.6% and 13.3% in the RIRS and micro-perc groups, respectively (p = 0.675). Hospital stay and radiation exposure were significantly lower in the RIRS group (all p stones in children, with comparable success and complication rates. Patients and their parents should be informed about the currently available treatment options, and of their efficacy and safety. However, further clinical trials are needed to support these results.

  8. Pediatric retrograde intra-renal surgery for renal stones <2 cm in solitary kidney.

    Science.gov (United States)

    Gamal, Wael Mohamed; Hussein, Mohamed M; Rashed, El Nisr; Mohamed, Al-Dahshoury; Mmdouh, Ahmed; Fawzy, Farag

    2016-01-01

    Management of renal stones in children with a solitary kidney is a challenge. In the current study, the efficacy and safety of retrograde intrarenal surgery (RIRS) in these children were determined. Records of children with renal stones who were treated at our institute between August 2011 and August 2014 were retrospectively assessed. Inclusion criteria were: Children with single renal stone <2 cm size, in a solitary kidney. A 7.5 Fr flexible ureteroscope (FURS) was introduced into the ureter over a hydrophilic guidewire under visual and fluoroscopic guidance - applying a back-loading technique. The stone was completely dusted using 200 μm laser fiber (0.2-0.8 joules power and 10-30 Hz frequency). At the end of the maneuver, a 5 Fr JJ stent was inserted into the ureter. The children were discharged home 24 h postoperative - provided that no complications were detected. Fourteen children (3 girls and 11 boys) with median age 9.5 years (range 6-12) were included. The mean stone burden was 12.2 ± 1.5 mm (range 9-20). Stones were successfully accessed in all of the cases by the FURS except for 2 cases in whom a JJ stent was inserted into the ureter and left in place for 2 weeks to achieve passive dilatation. All of the stones were dusted completely. The immediate postoperative stone-free rate (SFR) was 79%, and the final SFR was 100% after 3 weeks. No intraoperative complications were observed. RIRS for renal stone <2 cm in children with a solitary kidney is a single-session procedure with a high SFR, low complication rate, and is a minimally invasive, natural orifice technique.

  9. Prediction of development and maintenance of high albuminuria during chronic renin-angiotensin suppression by plasma proteomics.

    Science.gov (United States)

    Baldan-Martin, Montserrat; de la Cuesta, Fernando; Alvarez-Llamas, Gloria; Gonzalez-Calero, Laura; Ruiz-Hurtado, Gema; Moreno-Luna, Rafael; Mourino-Alvarez, Laura; Sastre-Oliva, Tamara; Segura, Julian; Padial, Luis R; Vivanco, Fernando; Ruilope, Luis M; Barderas, Maria G

    2015-10-01

    High albuminuria is a strong predictor of development of cardiovascular events in hypertensive patients. The search for predictors identifying patients at risk of developing high albuminuria or presenting a more rapid progression in this parameter may represent an effective strategy for adequate intervention and better outcome. Initially we investigated 24 patients presenting with normoalbuminuria, de novo albuminuria and sustained albuminuria. Plasma proteomics disclosed an upregulation of ceruloplasmin (CP), haptoglobin (HP) and alpha 1-acid glycoprotein (ORM1) that in a second step were selected for validation using turbidimetry assay in a cohort of 105 subjects. The validation showed that HP and ORM1 proteins were increased in patients presenting with very high albuminuria and potential irreversible kidney damage. CP and HP correlated positively with albuminuria values in normoalbuminuric patients. Finally, the levels of ORM1 and CP were increased in patients who progressed in their levels of albuminuria. Our findings show that these proteins may potentially be useful for predicting the development of high albuminuria and to monitor renal damage. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Intrarenal blood flow distribution in dog kidney determined by /sup 99m/Tc microaggregates and 201Tl

    International Nuclear Information System (INIS)

    Abildgaard, U.; Amtorp, O.; Gyring, J.; Daugaard, G.; Larsen, B.

    1988-01-01

    Intrarenal distribution of blood flow was assessed with radioactive albumin microaggregates (MA) in three cortical zones of the dog kidney. The experimentally obtained zonal fractions of total renal blood flow were compared with predicted zonal blood flow fractions obtained in a mathematical model. The maximal degree of skimming that could possibly occur in a single experiment was estimated. The analysis showed that local blood flow in the inner cortical zone was maximally underestimated by 17% because of skimming of MA, and in the outer cortical zone the blood flow was maximally overestimated by 13% with the method of radioactive MA uptake. Renal uptake of 201 Tl was measured simultaneously in exactly the same locations. Paired measurements of intrarenal blood flow distribution by MA and Tl uptake methodologies showed that local blood flow assessed with MA in the inner cortical zone was significantly lower than that obtained with 201 Tl and that a higher blood flow rate was obtained in the outer cortical zone with MA compared with 201 Tl. This disparity could be accounted for by the effect of skimming of MA as predicted by the model

  11. Re: Percutaneous Nephrolithotomy Versus Retrograde Intrarenal Surgery: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    De S

    2016-03-01

    Full Text Available Debate still goes on about minimally invasive treatment of urolithiasis. Meta-analysis is very important in decision-making; the level of evidence 1a represents evidence obtained from meta-analysis of randomized trials. This meta-analysis represented by De et al. reviewed the results of ten studies comparing minimicro percutaneous nephrolithotomy (mmPNL with retrograde intrarenal surgery (RIRS. A subgroup analysis was performed comparing standard PCNL and minimally invasive percutaneous procedures (MIPPs including mini-PCNL and micro-PCNL with RIRS, separately. Half of the studies were from Turkey. All stone burdens in these studies were lower than 2 cm except in two studies. Similarly, single stone was treated in all except for two studies. There were major differences between studies in terms of surgical techniques, follow-up procedure and imaging and definition of stone free or, in other words, clinically insignificant residual fragment. Operation time was same for RIRS and sPNL which might be because of the smaller size of stones for PNL, a debatable point. In patients with single stone about 2 cm, not surprisingly, sPNL was the leading one in stone free rates. There was a statistical confusion for other methods. According to original paper, RIRS was second one but if searched again; we can see the ‘corrigendum’ which reflected that stone free rate of mmPNL was higher than RIRS due to the correction of statistical mistake. In a special comparison between mmPNL and RIRS; RIRS had lower morbidity with lower stone free rates. Thus, as a conclusion, if the question is stone free rate, sPNL should be chosen but RIRS had the lowest morbidity with very close stone free rates to mmPNL. Although this type of studies are very important; this study did not meet expectations in decision making. It should be better to follow the European Association of Urology guidelines recommendations with evaluating whole criteria, such as comorbidities of the

  12. [Retrograde intrarenal surgery (RIRS). Technical complement for cases of acute lithiasis].

    Science.gov (United States)

    Amón, J H; Cepeda, M; Conde, C; Alonso, D; González, V; Martínez-Sagarra, J M

    2011-02-01

    Washing the renal cavities using minipercutaneous surgery shaft is an ideal technical procedure for retrograde intrarenal surgery (RIRS) when lithiasic fragmentation is significant or if the anatomy of the renal cavities may obstruct the spontaneous elimination of fragments. we performed 37 RIRS on 35 patients with renal lithiasis (14 men, 21 women) with a mean age of 56 (range 33-72) years, divided into two groups in accordance with the size of their kidney stones. Group A, 23 patients with lithiasis lithiasis >1.5 cm. 28 patients had a single kidney stone and 7 had multiple stones. Flexible uretrorenoscopy, 7.5 Fr (Flex-X(®, Karl Storz) by means of a ureteral access sheath. Holmium laser lithotripsy (Calculase®, Karl Storz) using 200 and 365 micrometer fibres. Fragment extraction with 1.7 Fr nitinol baskets (N-gage, Cook). In cases of significant fragmented stone burden, the renal cavities were washed with low-pressure fluid irrigation using a ureteral access sheath, which was collected together with the stone fragments carried by the "mini-perc" sheath (Ultrax-x® 18Fr, Cook; Rusch, 14 Fr) placed under radiologic and endoscopic control at the level of the calyx-papilla selected for fragment drainage. the mean diameter for group A was 9.13 (range 5-13) mm and 20.25 (range 16-28) mm for group B. The overall mean operating time was 81 (range 30-160) min. Group A required 66.43±35.18 min. and group B 107.5±46.73 min. (p=0.006). The rate of absence of stones immediately after surgery was 83.2%, 93.1% at 3 months (95.6% for A and 83.3% for B; p=0.217). In no case was ureteral stenosis observed as a result of the use of ureteral access sheaths. In 7 group B patients (58.3%) with acute lithiasis and/or alteration in their pyelocaliceal anatomy, we performed active lavage of the renal cavities applying the aforementioned percutaneous technique. The mean post-surgery hospital stay was 2.1 (range 1-4) days. There were post-surgery complications (Clavien 1) in 7

  13. Altered renal expression of angiotensin II receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats.

    Science.gov (United States)

    Schulman, Ivonne Hernandez; Zhou, Ming-Sheng; Treuer, Adriana V; Chadipiralla, Kiranmai; Hare, Joshua M; Raij, Leopoldo

    2010-01-01

    The susceptibility to fibrosis and progression of renal disease is mitigated by inhibition of the renin-angiotensin system (RAS). We hypothesized that activation of the intrarenal RAS predisposes to renal fibrosis in aging. Intrarenal expression of angiotensin II type 1 (AT(1)R), type 2 (AT(2)R), and (pro)renin receptors, ACE and ACE-2, as well as pro- and antioxidant enzymes were measured in 3-month-old (young), 14-month-old (middle-aged), and 24-month-old (old) male Sprague-Dawley rats. Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT(1)R /AT(2)R ratios were increased in middle-aged (cortical 1.6-fold, medullary 5-fold) and old rats (cortical 2-fold, medullary 4-fold). Similarly, (pro)renin receptor expression was increased in middle-aged (cortical 2-fold, medullary 3-fold) and old (cortical 5-fold, medullary 3-fold) rats. Cortical ACE was increased (+35%) in old rats, whereas ACE-2 was decreased (-50%) in middle-aged and old rats. NADPH oxidase activity was increased (2-fold), whereas antioxidant capacity and expression of the mitochondrial enzyme manganese superoxide dismutase (cortical -40%, medullary -53%) and medullary endothelial nitric oxide synthase (-48%) were decreased in old rats. Age-related intrarenal activation of the RAS preceded the development of severe renal fibrosis, suggesting that it contributes to the increased susceptibility to renal injury observed in the elderly. Copyright © 2010 S. Karger AG, Basel.

  14. Central injection of captopril inhibits the blood pressure response to intracerebroventricular choline

    Directory of Open Access Journals (Sweden)

    N. Isbil-Buyukcoskun

    2001-06-01

    Full Text Available In the present study, we investigated the involvement of the brain renin-angiotensin system in the effects of central cholinergic stimulation on blood pressure in conscious, freely moving normotensive rats. In the first step, we determined the effects of intracerebroventricular (icv choline (50, 100 and 150 µg on blood pressure. Choline increased blood pressure in a dose-dependent manner. In order to investigate the effects of brain renin-angiotensin system blockade on blood pressure increase induced by choline (150 µg, icv, an angiotensin-converting enzyme inhibitor, captopril (25 and 50 µg, icv, was administered 3 min before choline. Twenty-five µg captopril did not block the pressor effect of choline, while 50 µg captopril blocked it significantly. Our results suggest that the central renin-angiotensin system may participate in the increase in blood pressure induced by icv choline in normotensive rats.

  15. Angiotensin II, tissue factor and the thrombotic paradox of hypertension.

    Science.gov (United States)

    Celi, Alessandro; Cianchetti, Silvana; Dell'Omo, Giulia; Pedrinelli, Roberto

    2010-12-01

    Tissue factor (TF), the physiologic initiator of blood coagulation, may contribute to the increased risk of thrombotic complications that characterizes arterial hypertension, as suggested by hypertensive animal models showing evidence for TF activation, and clinical studies in hypertensive patients at higher cardiovascular risk with increased circulating levels of TF and thrombogenic microparticles. Angiotensin II stimulates TF expression both in vitro and in vivo, an effect abolished by ACE or angiotensin II receptor inhibition. Moreover, renin-angiotensin system blockers, including aliskiren, a direct renin inhibitor, are able to modulate TF expression in monocytes and vascular endothelial cells activated by inflammatory cytokines. This behavior is suggestive of anti-inflammatory and anti-thrombotic properties of renin-angiotensin system blockers, and is compatible with the possibility that blocking local renin-angiotensin system activation might downregulate TF, thus reducing the risk of ischemic complications in hypertensive patients.

  16. IgG4-related Disease: A Mass Lesion in the Intrarenal Sinus near the Renal Pelvis.

    Science.gov (United States)

    Inenaga, Jun-Ichi; Ueno, Toshiharu; Kawada, Masahiro; Imafuku, Aya; Mise, Koki; Sumida, Keiichi; Hiramatsu, Rikako; Hasegawa, Eiko; Hayami, Noriko; Suwabe, Tatsuya; Hoshino, Junichi; Sawa, Naoki; Takaichi, Kenmei; Fujii, Takeshi; Ohashi, Kenichi; Okaneya, Toshikazu; Ubara, Yoshifumi

    2015-01-01

    A 52-year-old Japanese woman was admitted to our hospital with the renal pelvic mass lesion detected on a health screening examination. The surgical specimen contained a mass exhibiting the histological features of immunoglobulin (Ig)G4-related disease, including lymphoplasmacytic infiltration and sclerosis with numerous IgG4-producing plasma cells. Postoperatively, an elevation of the serum IgG4 level was confirmed at 403 mg/dL; however, there was no evidence of tubulointerstitial nephritis or glomerulopathy, including membranous nephropathy, and the urothelium of the renal pelvis was intact without inflammation. We herein report this case in which IgG4-related disease of the renal pelvic region presented with a mass lesion in the intrarenal sinus near the renal pelvis, not 'pyelitis' (as described by Stone).

  17. The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, Stine; Rossing, Kasper; Hess, Georg

    2012-01-01

    Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid-binding p......Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid...

  18. 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...

  19. R1 autonomic nervous system in acute kidney injury.

    Science.gov (United States)

    Hering, Dagmara; Winklewski, Pawel J

    2017-02-01

    Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin-angiotensin-aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti-inflammatory effects and modulation of centrally-mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti-inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre-clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented. © 2016 John Wiley & Sons Australia, Ltd.

  20. Intrarenal transfer of an intracellular fluorescent fusion of angiotensin II selectively in proximal tubules increases blood pressure in rats and mice

    Science.gov (United States)

    Li, Xiao C.; Cook, Julia L.; Rubera, Isabelle; Tauc, Michel; Zhang, Fan

    2011-01-01

    The present study tested the hypothesis that intrarenal adenoviral transfer of an intracellular cyan fluorescent fusion of angiotensin II (ECFP/ANG II) selectively in proximal tubules of the kidney increases blood pressure by activating AT1 (AT1a) receptors. Intrarenal transfer of ECFP/ANG II was induced in the superficial cortex of rat and mouse kidneys, and the sodium and glucose cotransporter 2 (sglt2) promoter was used to drive ECFP/ANG II expression selectively in proximal tubules. Intrarenal transfer of ECFP/ANG II induced a time-dependent, proximal tubule-selective expression of ECFP/ANG II in the cortex, which peaked at 2 wk and was sustained for 4 wk. ECFP/ANG II expression was low in the glomeruli and the entire medulla and was absent in the contralateral kidney or extrarenal tissues. At its peak of expression in proximal tubules at day 14, ANG II was increased by twofold in the kidney (P tubules (P kidney, and proximal tubule ANG II, or sodium excretion. These results provide evidence that proximal tubule-selective transfer of an intracellular ANG II fusion protein increases blood pressure by activating AT1a receptors and increasing sodium reabsorption in proximal tubules. PMID:21307128

  1. RETRACTED: Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population.

    Science.gov (United States)

    Zhou, Tian-Biao; Guo, Xue-Feng; Jiang, Zongpei; Li, Hong-Yan

    2015-12-01

    The following article has been included in a multiple retraction: Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang, and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population Journal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi: 10.1177/1470320314563425 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January

  2. RETRACTED: Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression.

    Science.gov (United States)

    Yang, Chun-Hua; Zhou, Tian-Biao

    2015-12-01

    This article has been included in a multiple retraction: Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression Journal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi: 10.1177/1470320314568521 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 Tian-Biao Zhou, Xue-Feng Guo, Zongpei

  3. RETRACTED: Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population.

    Science.gov (United States)

    Zhong, Weiqiang; Jiang, Zongpei; Zhou, Tian-Biao

    2015-12-01

    This article has been included in a multiple retraction: Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10

  4. RETRACTED: Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy.

    Science.gov (United States)

    Tang, Wenzhuang; Zhou, Tian-Biao; Jiang, Zongpei

    2015-12-01

    This article has been included in a multiple retraction: Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10

  5. RETRACTED: Relationship between the angiotensinogen A1166C gene polymorphism and the risk of diabetes mellitus developing into diabetic nephropathy.

    Science.gov (United States)

    Yang, Chun-Hua; Zhou, Tian-Biao

    2015-12-01

    This article has been included in a multiple retraction: Chun-Hua Yang and Tian-Biao Zhou Relationship between the angiotensinogen A1166C gene polymorphism and the risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314566221, first published on February 1, 2015 doi: 10.1177/1470320314566221 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10

  6. N-Acetyl Cysteine Attenuated the Deleterious Effects of Advanced Glycation End-Products on the Kidney of Non-Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Karina Thieme

    2016-11-01

    Full Text Available Aim: To assess the renal effects of chronic exposure to advanced glycation end-products (AGEs in the absence of diabetes and the potential impact of concomitant treatment with the antioxidant N-acetyl cysteine (NAC. Methods: Wistar rats received intraperitoneally 20 mg/kg/day of albumin modified (AlbAGE or not (AlbC by advanced glycation for 12 weeks and oral NAC (600mg/L; AlbAGE+NAC and AlbC+NAC, respectively. Biochemical, urinary and renal morphological analyses; carboxymethyl-lysine (CML, an AGE, CD68 (macrophage infiltration, and 4-hydroxynonenal (4-HNE, marker of oxidative stress immunostaining; intrarenal mRNA expression of genes belonging to pathways related to AGEs (Ager, Ddost, Nfkb1, renin-angiotensin system (Agt, Ren, Ace, fibrosis (Tgfb1, Col4a1, oxidative stress (Nox4, Txnip, and apoptosis (Bax, Bcl2; and reactive oxidative species (ROS content were performed. Results: AlbAGE significantly increased urine protein-to-creatinine ratio; glomerular area; renal CML content and macrophage infiltration; expression of Ager, Nfkb1, Agt, Ren, Tgfb1, Col4a1, Txnip, Bax/Bcl2 ratio; and 4-HNE and ROS contents. Some of these effects were attenuated by NAC concomitant treatment. Conclusion: Because AGEs are highly consumed in modern diets and implicated in the progression of different kidney diseases, NAC could be a therapeutic intervention to decrease renal damage, considering that long-term restriction of dietary AGEs is difficult to achieve in practice.

  7. When stenting in renal artery stenosis? Update on pathophysiology of ischemic nephropathy and management strategies

    Directory of Open Access Journals (Sweden)

    Alessandro Zuccalà

    2013-11-01

    Full Text Available In recent years, decisions taken on the optimal management of patients with renal artery stenosis have triggered off controversy and debate among clinicians dealing with renovascular disease. The main reason underlying this ongoing controversy may be the heterogeneity of the clinical entities that are normally associated with the umbrella definition of renal artery stenosis. Indeed a causal link between the stenosis and its clinical consequences (i.e. hypertension, renal failure can often demonstrated in some entities, such as fibromuscular dysplasia, truncal stenosis or arterial stenosis in the transplanted kidney, which can be defined as pure renal artery stenosis. On the contrary, the entity generally called ostial stenosis is a disease of the abdominal aorta where it encroaches the ostium of the renal artery at the end of a long process involving the entire vascular tree. Patients affected by ostial stenosis also suffer from generalized atherosclerosis, and kidney damage is often caused by the atherosclerotic environment with the stenosis acting as an innocent bystander. This may account for the low rate of renal function recovery in subjects with ostial stenosis. In our view, keeping the different entities separate along with a careful understanding of the mechanisms underpinning renal damage, particularly the intrarenal activation of the renin angiotensin system which in turn induces renal inflammation and oxidative stress, may enable clinicians to make the right decisions in regard to revascularization.

  8. Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children.

    Science.gov (United States)

    Morato, Manuela; Correia-Costa, Liane; Sousa, Teresa; Cosme, Dina; Schaefer, Franz; Areias, José Carlos; Guerra, António; Afonso, Alberto Caldas; Barros, Henrique; Azevedo, Ana; Albino-Teixeira, António

    2017-08-01

    We aimed to study the impact of obesity on urinary excretion of angiotensinogen (U-AGT) in prepubertal children, focusing on the duration of obesity and gender. Also, we aimed to evaluate whether plasma angiotensinogen (P-AGT) and hydrogen peroxide (H 2 O 2 ) play a role in the putative association. Cross-sectional evaluation of 305 children aged 8-9 years (160 normal weight, 86 overweight, and 59 obese). Anthropometric measurements and 24-h ambulatory blood pressure monitoring were performed. Angiotensinogen (AGT) was determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit and H 2 O 2 by a microplate fluorometric assay. U-AGT and P-AGT levels were similar across body mass index (BMI) groups and between sexes. However, boys who were overweight/obese since the age of 4 years presented lower levels of U-AGT compared with those of normal weight at the same age. In children who were overweight/obese since the age of 4, urinary H 2 O 2 decreased with P-AGT. A higher duration of obesity was associated with decreased U-AGT in boys, thus reflecting decreased intrarenal activity of the renin-angiotensin system. Also, children with a longer duration of obesity showed an inverse association between urinary H 2 O 2 and P-AGT. Future studies should address whether these results reflect an early compensatory mechanism to limit obesity-triggered renal dysfunction.

  9. Role of TGF-alpha in the progression of diabetic kidney disease.

    Science.gov (United States)

    Heuer, Josef G; Harlan, Shannon M; Yang, Derek D; Jaqua, Dianna L; Boyles, Jeffrey S; Wilson, Jonathan M; Heinz-Taheny, Kathleen M; Sullivan, John M; Wei, Tao; Qian, Hui-Rong; Witcher, Derrick R; Breyer, Matthew D

    2017-06-01

    Transforming growth factor-alpha (TGFA) has been shown to play a role in experimental chronic kidney disease associated with nephron reduction, while its role in diabetic kidney disease (DKD) is unknown. We show here that intrarenal TGFA mRNA expression, as well as urine and serum TGFA, are increased in human DKD. We used a TGFA neutralizing antibody to determine the role of TGFA in two models of renal disease, the remnant surgical reduction model and the uninephrectomized (uniNx) db/db DKD model. In addition, the contribution of TGFA to DKD progression was examined using an adeno-associated virus approach to increase circulating TGFA in experimental DKD. In vivo blockade of TGFA attenuated kidney disease progression in both nondiabetic 129S6 nephron reduction and Type 2 diabetic uniNx db/db models, whereas overexpression of TGFA in uniNx db/db model accelerated renal disease. Therapeutic activity of the TGFA antibody was enhanced with renin angiotensin system inhibition with further improvement in renal parameters. These findings suggest a pathologic contribution of TGFA in DKD and support the possibility that therapeutic administration of neutralizing antibodies could provide a novel treatment for the disease. Copyright © 2017 the American Physiological Society.

  10. Hemodynamic and tubular changes induced by contrast media.

    Science.gov (United States)

    Caiazza, Antonella; Russo, Luigi; Sabbatini, Massimo; Russo, Domenico

    2014-01-01

    The incidence of acute kidney injury induced by contrast media (CI-AKI) is the third cause of AKI in hospitalized patients. Contrast media cause relevant alterations both in renal hemodynamics and in renal tubular cell function that lead to CI-AKI. The vasoconstriction of intrarenal vasculature is the main hemodynamic change induced by contrast media; the vasoconstriction is accompanied by a cascade of events leading to ischemia and reduction of glomerular filtration rate. Cytotoxicity of contrast media causes apoptosis of tubular cells with consequent formation of casts and worsening of ischemia. There is an interplay between the negative effects of contrast media on renal hemodynamics and on tubular cell function that leads to activation of renin-angiotensin system and increased production of reactive oxygen species (ROS) within the kidney. Production of ROS intensifies cellular hypoxia through endothelial dysfunction and alteration of mechanisms regulating tubular cells transport. The physiochemical characteristics of contrast media play a critical role in the incidence of CI-AKI. Guidelines suggest the use of either isoosmolar or low-osmolar contrast media rather than high-osmolar contrast media particularly in patients at increased risk of CI-AKI. Older age, presence of atherosclerosis, congestive heart failure, chronic renal disease, nephrotoxic drugs, and diuretics may multiply the risk of CI-AKI.

  11. The Renal Protective Effect of Jiangya Tongluo Formula, through Regulation of Adrenomedullin and Angiotensin II, in Rats with Hypertensive Nephrosclerosis

    Directory of Open Access Journals (Sweden)

    Lin Han

    2015-01-01

    Full Text Available We investigated the effect of Jiangya Tongluo (JYTL formula on renal function in rats with hypertensive nephrosclerosis. A total of 21 spontaneously hypertensive rats (SHRs were randomized into 3 groups: valsartan (10 mg/kg/d valsartan, JYTL (14.2 g/kg/d JYTL, and a model group (5 mL/kg/d distilled water; Wistar Kyoto rats comprised the control group (n = 7, 5 mL/kg/d distilled water. Treatments were administered by gavage every day for 8 weeks. Blood pressure, 24-h urine protein, pathological changes in the kidney, serum creatinine, and blood urea nitrogen (BUN levels were estimated. The contents of adrenomedullin (ADM and angiotensin II (Ang II in both the kidney and plasma were evaluated. JYTL lowered BP, 24-h urine protein, serum creatinine, and BUN. ADM content in kidneys increased and negatively correlated with BP, while Ang II decreased and negatively correlated with ADM, but there was no statistically significant difference of plasma ADM between the model and the treatment groups. Possibly, activated intrarenal renin-angiotensin system (RAS plays an important role in hypertensive nephrosclerosis and the protective function of ADM via local paracrine. JYTL may upregulate endogenous ADM level in the kidneys and antagonize Ang II during vascular injury by dilating renal blood vessels.

  12. Interaction of the endocrine system with inflammation: a function of energy and volume regulation.

    Science.gov (United States)

    Straub, Rainer H

    2014-02-13

    During acute systemic infectious disease, precisely regulated release of energy-rich substrates (glucose, free fatty acids, and amino acids) and auxiliary elements such as calcium/phosphorus from storage sites (fat tissue, muscle, liver, and bone) are highly important because these factors are needed by an energy-consuming immune system in a situation with little or no food/water intake (sickness behavior). This positively selected program for short-lived infectious diseases is similarly applied during chronic inflammatory diseases. This review presents the interaction of hormones and inflammation by focusing on energy storage/expenditure and volume regulation. Energy storage hormones are represented by insulin (glucose/lipid storage and growth-related processes), insulin-like growth factor-1 (IGF-1) (muscle and bone growth), androgens (muscle and bone growth), vitamin D (bone growth), and osteocalcin (bone growth, support of insulin, and testosterone). Energy expenditure hormones are represented by cortisol (breakdown of liver glycogen/adipose tissue triglycerides/muscle protein, and gluconeogenesis; water retention), noradrenaline/adrenaline (breakdown of liver glycogen/adipose tissue triglycerides, and gluconeogenesis; water retention), growth hormone (glucogenic, lipolytic; has also growth-related aspects; water retention), thyroid gland hormones (increase metabolic effects of adrenaline/noradrenaline), and angiotensin II (induce insulin resistance and retain water). In chronic inflammatory diseases, a preponderance of energy expenditure pathways is switched on, leading to typical hormonal changes such as insulin/IGF-1 resistance, hypoandrogenemia, hypovitaminosis D, mild hypercortisolemia, and increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Though necessary during acute inflammation in the context of systemic infection or trauma, these long-standing changes contribute to increased mortality in chronic

  13. Comparison of retrograde intrarenal surgery, shockwave lithotripsy, and percutaneous nephrolithotomy for treatment of medium-sized radiolucent renal stones.

    Science.gov (United States)

    Resorlu, Berkan; Unsal, Ali; Ziypak, Tevfik; Diri, Akif; Atis, Gokhan; Guven, Selcuk; Sancaktutar, Ahmet Ali; Tepeler, Abdulkadir; Bozkurt, Omer Faruk; Oztuna, Derya

    2013-12-01

    To compare the outcomes of shock wave lithotripsy (SWL), percutaneous nephrolithotomy (PNL), and retrograde intrarenal surgery (RIRS) for 10-20 mm radiolucent renal calculi by evaluating stone-free rates and associated complications. A total of 437 patients at 7 institutions who underwent SWL (n = 251), PNL (n = 140), or RIRS (n = 46) were enrolled in our study. Clinical success was defined as stone-free status or asymptomatic insignificant residual fragments PNL, and RIRS (p PNL and RIRS (21.9 vs 5.7 vs 8.7%, respectively; p PNL, and RIRS were 7.6, 22.1, and 10.9%, respectively (p PNL group received blood transfusions, while none of the patients in RIRS and SWL groups transfused. Hospitalization time per patient was 1.3 ± 0.5 days in the RIRS group, while it was 2.6 ± 0.9 days in the PNL group (p PNL group compared to RIRS (145.7 ± 101.7 vs 28.7 ± 18.7 s, and 57.5 ± 22.1 vs 43.1 ± 17 min, respectively). For treatment of moderate-sized radiolucent renal stones, RIRS and PNL provide significantly higher success and lower retreatment rate compared with SWL. Although PNL is effective, its biggest drawback is its invasiveness. Blood loss, radiation exposure, hospital stay, and morbidities of PNL can be significantly reduced with RIRS technique.

  14. Treatment of Moderate Sized Renal Pelvis Calculi: Stone Clearance Time Comparison of Extracorporeal Shock Wave Lithotripsy and Retrograde Intrarenal Surgery.

    Science.gov (United States)

    Ercil, Hakan; Alma, Ergun; Bas, Okan; Sener, Nevzat Can; Vuruskan, Ediz; Kuyucu, Faruk; Unal, Umut; Gören, Mehmet Resit; Evliyaoglu, Yalcin

    2016-03-05

    To compare the stone clearance times in patients undergoing extracorporeal shock wave lithotripsy (SWL) or retrograde intrarenal surgery (RIRS) for single radiopaque renal pelvis stones 10-20 mm in size. The results of this study may guide urologists and patients and aid in selecting the optimal preoperative treatment. Between January 2013 and February 2015, we conducted a retrospective study and collected data from 333 patients treated with SWL (n = 172) or RIRS (n = 161). We included successfully treated patients with a single radiopaque renal pelvis stone 10-20 mm in size to calculate stone clearance times. The average stone size for the SWL group was 14.62 ± 2.58 mm and 14.91 ± 2.92 mm for the RIRS group. The mean Hounsfield unit (HU) of the patients was 585.40 ± 158.39 HU in the SWL group and 567.74 ± 186.85 HU in the RIRS group. Following full fragmentation, the mean stone clearance time was 26.55 ± 9.71 days in the SWL group and 11.59 ± 7.01 days in the RIRS group (P < .001). One of the most overlooked parameters in urinary stone treatments is stone clearance. We believe this study will shed light for those who aim to conduct larger randomized prospective studies. .

  15. Minimally Invasive Percutaneous Nephrolithotomy versus Retrograde Intrarenal Surgery for Upper Urinary Stones: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Hongyang Jiang

    2017-01-01

    Full Text Available Minimally invasive percutaneous nephrolithotomy (mini-PCNL and retrograde intrarenal surgery (RIRS are both alternatives for PCNL to treat renal calculi. This study is aimed at comparing the stone-free rate (SFR and other surgery parameters of two approaches for treating upper urinary calculi. We performed this meta-analysis in September 2016 by searching studies about mini-PCNL and RIRS for treating upper urinary calculi in various databases, and RevMan v.5.3 was applied. Three randomized controlled trials and ten nonrandomized trials were included, involving a total of 1317 patients. Meta-analysis showed that mini-PCNL group led to a higher SFR [odds ratio: 1.96; 95% confidence interval: 1.46–2.64; P<0.00001] but brought a larger postoperative decrease in hemoglobin levels compared with RIRS. RIRS provided a shorter hospital time. There was no significant difference in operation time. Higher postoperative complications were detected in the mini-PCNL, but the difference was not significant. Grade I and III complications did not vary between two procedures, but grade II complications were of lower incidence in RIRS group. In the light of these results, compared with RIRS, mini-PCNL provided significantly higher SFR and efficiency quotient for managing calculi; however, it resulted in higher incidence of postoperative complications, larger hemoglobin drops, and longer hospital stay.

  16. Regulation of cardiac beta-adrenergic receptors by captopril. Implications for congestive heart failure

    NARCIS (Netherlands)

    Maisel, A. S.; Phillips, C.; Michel, M. C.; Ziegler, M. G.; Carter, S. M.

    1989-01-01

    The interaction of the renin-angiotensin system and the sympathetic nervous system in patients with congestive heart failure is not well understood. We tested the hypothesis that angiotensin-converting enzyme inhibitors can resensitize the beta-adrenergic receptor system. Guinea pigs were given

  17. Angiotensin receptor-binding molecule in leukocytes in association with the systemic and leukocyte inflammatory profile.

    Science.gov (United States)

    Haruhara, Kotaro; Wakui, Hiromichi; Azushima, Kengo; Kurotaki, Daisuke; Kawase, Wataru; Uneda, Kazushi; Haku, Sona; Kobayashi, Ryu; Ohki, Kohji; Kinguchi, Sho; Ohsawa, Masato; Minegishi, Shintaro; Ishigami, Tomoaki; Matsuda, Miyuki; Yamashita, Akio; Nakajima, Hideaki; Tamura, Tomohiko; Tsuboi, Nobuo; Yokoo, Takashi; Tamura, Kouichi

    2018-02-01

    The components of the renin-angiotensin system in leukocytes is involved in the pathophysiology of non-communicable diseases (NCDs), including hypertension, atherosclerosis and chronic kidney disease. Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP) is an AT1R-specific binding protein, and is able to inhibit the pathological activation of AT1R signaling in certain animal models of NCDs. The aim of the present study was to investigate the expression and regulation of ATRAP in leukocytes. Human leukocyte ATRAP mRNA was measured with droplet digital polymerase chain reaction system, and analyzed in relation to the clinical variables. We also examined the leukocyte cytokines mRNA in bone-marrow ATRAP-deficient and wild-type chimeric mice after injection of low-dose lipopolysaccharide. The ATRAP mRNA was abundantly expressed in leukocytes, predominantly granulocytes and monocytes, of healthy subjects. In 86 outpatients with NCDs, leukocyte ATRAP mRNA levels correlated positively with granulocyte and monocyte counts and serum C-reactive protein levels. These positive relationships remained significant even after adjustment. Furthermore, the leukocyte ATRAP mRNA was significantly associated with the interleukin-1β, tumor necrosis factor-α and monocyte chemotactic protein-1 mRNA levels in leukocytes of NCDs patients. In addition, the leukocyte interleukin-1β mRNA level was significantly upregulated in bone marrow ATRAP-deficient chimeric mice in comparison to wild-type chimeric mice after injection of lipopolysaccharide. These results suggest that leukocyte ATRAP is an emerging marker capable of reflecting the systemic and leukocyte inflammatory profile, and plays a role as an anti-inflammatory factor in the pathophysiology of NCDs. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Effects of tilting on central hemodynamics and homeostatic mechanisms in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Nørgaard, Annette; Henriksen, Jens H

    2004-01-01

    Patients with cirrhosis have a hyperdynamic circulation and an abnormal blood volume distribution with central hypovolemia, an activated sympathetic nervous system (SNS) as well as the renin-angiotensin-aldosterone system (RAAS). As the hyperdynamic circulation in cirrhosis may be present only in...... the CBV less in patients with cirrhosis, and the results suggest a differential regulation of central hemodynamics in patients with cirrhosis....

  19. Beneficial effects of combined AT1 receptor/neprilysin inhibition (ARNI) versus AT1 receptor blockade alone in the diabetic eye

    NARCIS (Netherlands)

    Prasad, T. (Tuhina); L.C.W. Roksnoer (Lodi); P. Zhu (Ping); A. Verma (Amrisha); Li, Y. (Yiming); W.W. Batenburg (Wendy); de Vries, R. (René); A.H.J. Danser (Jan); Q. Li (Qiuhong)

    2016-01-01

    textabstractPURPOSE. Dysfunction of the renin-angiotensin system (RAS) contributes to pathogenesis of diabetic retinopathy (DR). Yet RAS blockers have only limited beneficial effects on progression of DR in clinical trials. The natriuretic peptide system offsets RAS, so that enhancing the activity

  20. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)

    NARCIS (Netherlands)

    McMurray, J.J.; Packer, M.; Desai, A.S.; Gong, J.; Lefkowitz, M.P.; Rizkala, A.R.; Rouleau, J.; Shi, V.C.; Solomon, S.D.; Swedberg, K.; Zile, M.R.; Bellersen, L.; et al.,

    2013-01-01

    AIMS: Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin-angiotensin-aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and

  1. Adjunctive therapy with statins reduces residual albuminuria/proteinuria and provides further renoprotection by downregulating the angiotensin II-AT1 pathway in hypertensive nephropathy.

    Science.gov (United States)

    Zhang, Zhi; Li, Ziqiang; Cao, Kaijin; Fang, Dailong; Wang, Fazhan; Bi, Gang; Yang, Jian; He, Yingju; Wu, Jinhui; Wei, Yuquan; Song, Xiangrong

    2017-07-01

    Blockade of the renin-angiotensin II (Ang II) system by AT1 blockers (ARBs) and angiotensin-converting enzyme inhibitors retards the progression of chronic kidney disease (CKD) by reducing albuminuria/proteinuria. However, many patients with CKD suffer from residual albuminuria/proteinuria, which is an independent risk factor for CKD progression. The aim of the current study is to investigate the effect of pitavastatin, one of the adjunctive agents to ARBs, on the reduction of albuminuria/proteinuria and further renoprotection mediated by telmisartan in spontaneously hypertensive rats. Forty-two-week-old spontaneously hypertensive rats were grouped randomly and received 8 weeks of treatments with vehicle, telmisartan, pitavastatin or a combination of telmisartan and pitavastatin. Both albuminuria and proteinuria were inhibited significantly in the telmisartan-treated group, but an obviously residual albuminuria was maintained. The combination treatment with telmisartan and pitavastatin displayed a more effective decrease in albuminuria and proteinuria, even to the normal level. Enhanced nephroprotection was also observed in this combination group, which was independent of the cholesterol-lowering effects. Further mechanistic studies revealed that the combination therapy greatly attenuated the expression of intrarenal Ang II and AT1, thereby decreasing the activation of TGF-β-Smad and NF-κB and inhibiting fibrosis and inflammation. Adjunctive therapy with pitavastatin dramatically reduced residual albuminuria/proteinuria and enhanced nephroprotection, likely by downregulating the expression of intrarenal Ang II and AT1. It could be concluded that statins might be a promising adjunctive therapeutic agent to conventional ARB treatment in hypertensive renal damage.

  2. Periconceptional undernutrition and being a twin each alter kidney development in the sheep fetus during early gestation.

    Science.gov (United States)

    MacLaughlin, Severence M; Walker, Simon K; Kleemann, David O; Tosh, Darran N; McMillen, I Caroline

    2010-03-01

    Adaptive growth responses of the embryo and fetus to nutritional restraint are important in ensuring early survival, but they are implicated in the programming of hypertension. It has been demonstrated that kidney growth and nephrogenesis are each regulated by intrarenal factors, including the insulin-like growth factors, glucocorticoids, and the renin-angiotensin system. Therefore, we have investigated the impact of periconceptional undernutrition (PCUN; from approximately 6 wk before to 7 days after conception) in singleton (control, n = 18; PCUN, n = 16) and twin pregnancies (control, n = 6; PCUN, n = 5) on the renal mRNA expression of 11beta- hydroxysteroid dehydrogensase type 1 and type 2 (11beta-HSD-1 and -2), the glucocorticoid (GR), and mineralocorticoid receptors, angiotensinogen, angiotensin receptor type 1 (AT1R) and 2 (AT2R), IGF-1 and IGF-2, and IGF1R and IGF2R at approximately 55 days gestation. There was no effect of PCUN or fetal number on fetal weight on relative kidney weight at approximately day 55 of gestation. There was an inverse relationship between the relative weight of the fetal kidney at approximately day 55 and maternal weight loss during the periconceptional period in fetuses exposed to PCUN. Exposure to PCUN resulted in a higher expression of IGF1 in the fetal kidney in singleton and twin pregnancies. Being a twin resulted in higher intrarenal expression of IGF-1 and IGF-2, GR, angiotensinogen, AT1R, and AT2R mRNA at 55 days gestation. Renal 11beta-HSD-2 mRNA expression was higher in PCUN singletons, but not PCUN twins, compared with controls. Thus, there may be an adaptive response in the kidney to the early environment of a twin pregnancy, which precedes the fetal growth restriction that occurs later in pregnancy. The kidney of the twin fetus exposed to periconceptional undernutrition may also be less protected from the consequences of glucocorticoid exposure.

  3. ECIRS (Endoscopic Combined Intrarenal Surgery) in the Galdakao-modified supine Valdivia position: a new life for percutaneous surgery?

    Science.gov (United States)

    Cracco, Cecilia Maria; Scoffone, Cesare Marco

    2011-12-01

    Percutaneous nephrolithotomy (PNL) is still the gold-standard treatment for large and/or complex renal stones. Evolution in the endoscopic instrumentation and innovation in the surgical skills improved its success rate and reduced perioperative morbidity. ECIRS (Endoscopic Combined IntraRenal Surgery) is a new way of affording PNL in a modified supine position, approaching antero-retrogradely to the renal cavities, and exploiting the full array of endourologic equipment. ECIRS summarizes the main issues recently debated about PNL. The recent literature regarding supine PNL and ECIRS has been reviewed, namely about patient positioning, synergy between operators, procedures, instrumentation, accessories and diagnostic tools, step-by-step standardization along with versatility of the surgical sequence, minimization of radiation exposure, broadening to particular and/or complex patients, limitation of post-operative renal damage. Supine PNL and ECIRS are not superior to prone PNL in terms of urological results, but guarantee undeniable anesthesiological and management advantages for both patient and operators. In particular, ECIRS requires from the surgeon a permanent mental attitude to synergy, standardized surgical steps, versatility and adherence to the ongoing clinical requirements. ECIRS can be performed also in particular cases, irrespective to age or body habitus. The use of flexible endoscopes during ECIRS contributes to minimizing radiation exposure, hemorrhagic risk and post-PNL renal damage. ECIRS may be considered an evolution of the PNL procedure. Its proposal has the merit of having triggered the critical analysis of the various PNL steps and of patient positioning, and of having transformed the old static PNL into an updated approach.

  4. The Effect of Stone Composition on the Efficacy of Retrograde Intrarenal Surgery: Kidney Stones 1 - 3 cm in Diameter.

    Science.gov (United States)

    Xue, Yuquan; Zhang, Peng; Yang, Xiaojie; Chong, Tie

    2015-05-01

    The goal of this study was to analyze the effect of stone composition on the efficacy of retrograde intrarenal surgery (RIRS) with kidney stones of 1-3 cm, 1-2 cm, and 2-3 cm in diameter. We undertook a retrospective analysis of 74 patients with kidney stones who underwent RIRS. The patients were divided into two groups based on stone composition: Group I (n=47) (calcium oxalate monohydrate and calcium phosphate) was the hard to fragment stone group and group II (n=27) (calcium oxalate dihydrate, magnesium ammonium phosphate, and uric acid) was the easy to fragment stone group. Forty-six patients with kidney stones 1 to 2 cm in diameter were divided into group A (n=30) (smaller than 20 mm, hard to fragment stones) and group B (n=16) (smaller than 20 mm, easy to fragment stones). Twenty-eight patients with stones 2 to 3 cm in diameter were divided into group C (n=17) (larger than 20 mm, hard to fragment stones) and group D (n=11) (larger than 20 mm, easy-to-crush stones). The stone clearance rates of group I and group II were 66.0% and 88.9%, respectively (Pstone clearance rates of group A and group B were 73.3% and 100% (Pstone clearance rates of group C and group D were 52.9% and 72.7%, respectively. Stone composition has a significant impact on the efficacy of RIRS in the management of 1 to 3 cm kidney stones. For 2-3 cm calcium oxalate dihydrate stones, uric acid stones, and magnesium ammonium phosphate stones, the outcome of RIRS treatment was relatively good, and RIRS is recommended.

  5. Systemic factors related to soluble (pro)renin receptor in plasma of patients with proliferative diabetic retinopathy.

    Science.gov (United States)

    Hase, Keitaro; Kanda, Atsuhiro; Hirose, Ikuyo; Noda, Kousuke; Ishida, Susumu

    2017-01-01

    (Pro)renin receptor [(P)RR], a new component of the tissue renin-angiotensin system (RAS), plays a crucial role in inflammation and angiogenesis in the eye, thus contributing to the development of proliferative diabetic retinopathy (PDR). In this study, we investigated systemic factors related to plasma levels of soluble form of (P)RR [s(P)RR] in patients with PDR. Twenty type II diabetic patients with PDR and 20 age-matched, non-diabetic patients with idiopathic macular diseases were enrolled, and plasma levels of various molecules were measured by enzyme-linked immunosorbent assays. Human retinal microvascular endothelial cells were stimulated with several diabetes-related conditions to evaluate changes in gene expression using real-time quantitative PCR. Of various systemic parameters examined, the PDR patients had significantly higher blood sugar and serum creatinine levels than non-diabetic controls. Protein levels of s(P)RR, prorenin, tumor necrosis factor (TNF)-α, complement factor D (CFD), and leucine-rich α-2-glycoprotein 1 (LRG1) significantly increased in the plasma of PDR subjects as compared to non-diabetes, with positive correlations detected between s(P)RR and these inflammatory molecules but not prorenin. Estimated glomerular filtration rate and serum creatinine were also correlated with plasma s(P)RR, but not prorenin, levels. Among the inflammatory molecules correlated with s(P)RR in the plasma, TNF-α, but not CFD or LRG1, application to retinal endothelial cells upregulated the mRNA expression of (P)RR but not prorenin, while stimulation with high glucose enhanced both (P)RR and prorenin expression. These findings suggested close relationships between plasma s(P)RR and diabetes-induced factors including chronic inflammation, renal dysfunction, and hyperglycemia in patients with PDR.

  6. Recent insights and therapeutic perspectives of angiotensin-(1-9) in the cardiovascular system.

    Science.gov (United States)

    Ocaranza, Maria Paz; Michea, Luis; Chiong, Mario; Lagos, Carlos F; Lavandero, Sergio; Jalil, Jorge E

    2014-11-01

    Chronic RAS (renin-angiotensin system) activation by both AngII (angiotensin II) and aldosterone leads to hypertension and perpetuates a cascade of pro-hypertrophic, pro-inflammatory, pro-thrombotic and atherogenic effects associated with cardiovascular damage. In 2000, a new pathway consisting of ACE2 (angiotensin-converting enzyme2), Ang-(1-9) [angiotensin-(1-9)], Ang-(1-7) [angiotensin-(1-7)] and the Mas receptor was discovered. Activation of this novel pathway stimulates vasodilation, anti-hypertrophy and anti-hyperplasia. For some time, studies have focused mainly on ACE2, Ang-(1-7) and the Mas receptor, and their biological properties that counterbalance the ACE/AngII/AT1R (angiotensin type 1 receptor) axis. No previous information about Ang-(1-9) suggested that this peptide had biological properties. However, recent data suggest that Ang-(1-9) protects the heart and blood vessels (and possibly the kidney) from adverse cardiovascular remodelling in patients with hypertension and/or heart failure. These beneficial effects are not modified by the Mas receptor antagonist A779 [an Ang-(1-7) receptor blocker], but they are abolished by the AT2R (angiotensin type 2 receptor) antagonist PD123319. Current information suggests that the beneficial effects of Ang-(1-9) are mediated via the AT2R. In the present review, we summarize the biological effects of the novel vasoactive peptide Ang-(1-9), providing new evidence of its cardiovascular-protective activity. We also discuss the potential mechanism by which this peptide prevents and ameliorates the cardiovascular damage induced by RAS activation.

  7. The Impact of Age-Related Dysregulation of the Angiotensin System on Mitochondrial Redox Balance

    Directory of Open Access Journals (Sweden)

    Ramya eVajapey

    2014-11-01

    Full Text Available Aging is associated with the accumulation of various deleterious changes in cells. According to the free radical and mitochondrial theory of aging, mitochondria initiate most of the deleterious changes in aging and govern life span. The failure of mitochondrial reduction-oxidation (redox homeostasis and the formation of excessive free radicals are tightly linked to dysregulation in the Renin Angiotensin System (RAS. A main rate-controlling step in RAS is renin, an enzyme that hydrolyzes angiotensinogen to generate angiotensin I. Angiotensin I is further converted to Angiotensin II (Ang II by angiotensin-converting enzyme (ACE. Ang II binds with equal affinity to two main angiotensin receptors—type 1 (AT1R and type 2 (AT2R. The binding of Ang II to AT1R activates NADPH oxidase, which leads to increased generation of cytoplasmic reactive oxygen species (ROS. This Ang II-AT1R–NADPH-ROS signal triggers the opening of mitochondrial KATP channels and mitochondrial ROS production in a positive feedback loop. Furthermore, RAS has been implicated in the decrease of many of ROS scavenging enzymes, thereby leading to detrimental levels of free radicals in the cell.AT2R is less understood, but evidence supports an anti-oxidative and mitochondria-protective function for AT2R. The overlap between age related changes in RAS and mitochondria, and the consequences of this overlap on age-related diseases are quite complex. RAS dysregulation has been implicated in many pathological conditions due to its contribution to mitochondrial dysfunction. Decreased age-related, renal and cardiac mitochondrial dysfunction was seen in patients treated with angiotensin receptor blockers. The aim of this review is to: (a report the most recent information elucidating the role of RAS in mitochondrial redox hemostasis and (b discuss the effect of age-related activation of RAS on generation of free radicals.

  8. Low sodium diet inhibits the local counter-regulator effect of angiotensin-(1-7) on angiotensin II

    NARCIS (Netherlands)

    Roks, Anton J M; Nijholt, Jeroen; van Buiten, Azuwerus; van Gilst, Wiek H; de Zeeuw, Dick; Henning, Robert H

    2004-01-01

    Objective The heptapeptide angiotensin-(1-7) [Ang-(1-7)] has been identified as a versatile, endogenous inhibitor of the renin-angiotensin system (RAS). As the therapeutic response to exogenous RAS inhibitors, such as AT, receptor antagonists, is altered by changes in salt intake, we investigated

  9. The effect of serum angiotensin II and angiotensin II type 1 receptor ...

    African Journals Online (AJOL)

    Ehab

    2012-06-18

    Jun 18, 2012 ... The effect of serum angiotensin II and angiotensin II type 1 receptor gene polymorphism on pediatric lupus nephritis. INTRODUCTION. Renin angiotensin system (RAS) has been considered one of the probable pathophysiologic mechanisms involved in SLE progression. However, the contribution of the ...

  10. Lack of relationship between an insertion/deletion polymorphism in the angiotensin I-converting enzyme gene and diabetic nephropathy and proliferative retinopathy in IDDM patients

    DEFF Research Database (Denmark)

    Tarnow, L; Cambien, Francois; Rossing, P

    1995-01-01

    Genotypic abnormalities of the renin-angiotensin system have been suggested as a risk factor for the development of diabetic nephropathy and proliferative retinopathy. We studied the relationship between an insertion(I)/deletion (D) polymorphism in the angiotensin-converting enzyme (ACE) gene in ...

  11. Renal and cardio-protective effects of direct renin inhibition : a systematic literature review

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo J.; Perkovic, Vlado; de Zeeuw, Dick

    2009-01-01

    Background Blockade of the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step by means of renin inhibition has led to the development of direct renin inhibitors (DRIs). Given the renal and cardioprotective effects of RAAS blockade by angiotensin-converting enzyme inhibitors and

  12. Improving the efficacy of RAAS blockade in patients with chronic kidney disease

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo J.; de Borst, Martin H.; Bakker, Stephan J. L.; Navis, Gerjan J.

    I Reduction of blood pressure and proteinuria by blockade of the renin-angiotensin-aldosterone system (RAAS) has been the cornerstone of renoprotective intervention for patients with chronic kidney disease (CKD) for many years. Despite the proven efficacy of RAAS blockade, however, the reduction in

  13. Expression and effect of inhibition of aminopeptidase-A during nephrogenesis.

    NARCIS (Netherlands)

    Dijkman, H.B.P.M.; Assmann, K.J.M.; Steenbergen, E.; Wetzels, J.F.M.

    2006-01-01

    Aminopeptidase-A (APA) is a metalloprotease that cleaves N-terminal aspartyl and glutamyl residues from peptides. Its best-known substrate is angiotensin II (Ang II), the most active compound of the renin-angiotensin system (RAS). The RAS is involved in renal development. Most components of the RAS

  14. Diagnostic potential of renal scintigraphy following ACE-inhibition ('captopril scintigraphy') for the detection of renovascular hypertension. Wertigkeit der Nierenszintigraphie unter ACE-Blockade ('Captoprilszintigraphie') in der Diagnostik der renovaskulaeren Hypertonie

    Energy Technology Data Exchange (ETDEWEB)

    Baum, R.P.; Maul, F.D.; Hoer, G. (Frankfurt Univ. (Germany). Abt. fuer Nuklearmedizin)

    1991-12-01

    The purpose of this paper is to: (a) briefly review the pathophysiological basis of renovascular hypertension and the renin-angiotensin-system; (b) to outline the potential of captopril scintigraphy especially using Tc-99m MAG{sub 3}; and (c) to propose a practical protocol for captopril scintigraphy and its role in screening for renovascular hypertension. (orig./MG).

  15. Oxidation as an important factor of protein damage: Implications for ...

    Indian Academy of Sciences (India)

    2015-04-20

    Apr 20, 2015 ... diabetes. Various hyperglycaemia-induced metabolic and he- modynamic imbalances (e.g. increased AGEs formation, oxi- dative stress, activation of protein kinase C, polyol pathway and renin-angiotensin system) are considered to contribute to the development and progression of diabetic nephropathy.

  16. An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function

    NARCIS (Netherlands)

    Holtkamp, Frank A.; de Zeeuw, Dick; Thomas, Merlin C.; Cooper, Mark E.; de Graeff, Pieter A.; Hillege, Hans J. L.; Parving, Hans-Henrik; Brenner, Barry M.; Shahinfar, Shahnaz; Lambers Heerspink, Hiddo J.

    Intervention in the renin-angiotensin-aldosterone-system (RAAS) is associated with slowing the progressive loss of renal function. During initiation of therapy, however, there may be an acute fall in glomerular filtration rate (GFR). We tested whether this initial fall in GFR reflects a renal

  17. Use of angiotensin II receptor blockers in children- a review of ...

    African Journals Online (AJOL)

    Background: The incidence of hypertension in the pediatric population has been increasing. Childhood blood pressure is predictive of adult BP. The renin angiotensin aldosterone system pathway is important in the mediation of pediatric hypertension. New therapies approved for adults are often used off label in children ...

  18. The role of angiotensin(1-7) in renal vasculature of the rat

    NARCIS (Netherlands)

    van der Wouden, Els A.; Ochodnický, Peter; van Dokkum, Richard Pe; Roks, Anton Jm; Deelman, Leo E.; de Zeeuw, Dick; Henning, Robert H.

    2006-01-01

    Angiotensin(1-7) is an active component of the renin-angiotensin-aldosterone system. Its exact role in renal vascular function is unclear. We therefore studied the effects of angiotensin(1-7) on the renal vasculature in vitro and in vivo. Isolated small renal arteries were studied in an arteriograph

  19. Angiotensin-(1-7) : Pharmacological properties and pharmacotherapeutic perspectives

    NARCIS (Netherlands)

    Iusuf, Dilek; Henning, Robert H.; van Gilst, Wiek H.; Roks, Anton J. M.

    2008-01-01

    Therapeutic modulation of the renin-angiotensin system is not complete without taking into consideration the beneficial effects of angiotensin-(1-7) in cardiovascular pathology. Various pharmacological pathways are already exploited to involve this heptapeptide in therapy as both inhibitors of

  20. Angiotensin II type 1 receptor (A1166C) gene polymorphism in ...

    African Journals Online (AJOL)

    Abstract. Background: Genetic variability in the genes of different components of renin-angiotensin system (RAS) is likely to contribute for its heterogenous association in renal diseased patients. Among the candidate genes of RAS, angiotensin II type 1 receptor gene polymorphism (AT1R A1166C) seems to be particularly ...

  1. A comparative study to determine the clinical efficacy of Ramipril ...

    African Journals Online (AJOL)

    Inhibition of the renin-angiotensin system causes a reduction in urinary protein excretion. It is uncertain whether Angiotensin receptor blockers (ARBs) are equally effective antiproteinuric agents as Angiotensin converting Enzyme (ACE) inhibitors, or whether the combination of ACE inhibitors with ARBs is preferable to ACE ...

  2. Release of beta-lipotropin- and beta-endorphin-like material induced by angiotensin in the conscious rat

    NARCIS (Netherlands)

    Beuers, U.; HERTTING, G.; KNEPEL, W.

    1982-01-01

    1 The influence of the renin-angiotensin system on plasma beta-endorphin-like immunoreactivity (beta-EI) was investigated in the conscious rat by use of a radioimmunoassay for beta-endorphin without prior extraction.2 Intravenous infusion of angiotensin I, II or (des-1-Asp)angiotensin II

  3. The role of angiotensin(1-7) in renal vasculature of the rat

    NARCIS (Netherlands)

    van der Wouden, Els A.; Ochodnicky, Peter; van Dokkum, Richard P. E.; Roks, Anton J. M.; Deelman, Leo E.; de Zeeuw, Dick; Henning, Robert H.

    2006-01-01

    Objective Angiotensin(1-7) is an active component of the renin-angiotensin-aldosterone system. Its exact role in renal vascular function is unclear. We therefore studied the effects of angiotensin(1-7) on the renal vasculature in vitro and in vivo. Methods Isolated small renal arteries were studied

  4. Hypertensive effect of bronchial asthma | Lutfi | Sudan Journal of ...

    African Journals Online (AJOL)

    Abstract. Background: Both bronchial asthma and hypertension are spastic disorders of smooth muscle, salt sensitive and sometimes associated with higher renin-angiotensin system activity, suggesting similarities between their aetiologies. This study was intended to assess the blood pressure status in asthmatic patients.

  5. Time for a comeback of NSAIDs in proteinuric chronic kidney disease?

    NARCIS (Netherlands)

    Vogt, L.; Laverman, G. D.; Navis, G.

    2010-01-01

    Before the introduction of renin-angiotensin-aldosterone system (RAAS) inhibitors in the 1980s, non-steroidal anti-inflammatory drugs (NSAIDs) were the only class of drugs available for the reduction of symptomatic proteinuria. Long-term data from those days suggested sustained renoprotective

  6. [Acute renal failure due to RAAS-inhibitors combined with dehydration].

    NARCIS (Netherlands)

    Scherpbier-de Haan, N.D.; Grauw, W.J.C. de; Wetzels, J.F.M.; Vervoort, G.M.M.

    2010-01-01

    Two men (61 and 81 years old) with mild impaired kidney function developed acute renal failure due to dehydration combined with the use of inhibitors of the renin-angiotensin-aldosterone system (RAAS). After rehydration, correction of hyperkalaemia and stopping RAAS-inhibition and diuretics, they

  7. Safe use of NSAIDs and RAS-inhibitors at Agogo Presbyterian Hospital, Ghana

    NARCIS (Netherlands)

    Meulendijks, L.G.; Adomako, E.A.; Appiah, E.B.; Kramers, C.

    2016-01-01

    BACKGROUND: Preventable adverse events of medication are an important cause of hospital admissions in the developed world, in which non-steroidal anti-inflammatory drugs (NSAIDs) and renin-angiotensin system (RAS-) inhibitors are frequently involved. NSAIDs and RAS-inhibitors are also often used in

  8. Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction

    NARCIS (Netherlands)

    Voors, Adriaan A.; Gori, Mauro; Liu, Licette C. Y.; Claggett, Brian; Zile, Michael R.; Pieske, Burkert; McMurray, John J. V.; Packer, Milton; Shi, Victor; Lefkowitz, Martin P.; Solomon, Scott D.

    BackgroundIncreases in serum creatinine with renin-angiotensin-aldosterone system (RAAS) inhibitors can lead to unnecessary discontinuation of these agents. The dual-acting angiotensin receptor neprilysin inhibitor LCZ696 improves clinical outcome patients with heart failure with reduced ejection

  9. Controlling Hypertension in Diabetic Patients | Familoni | Nigerian ...

    African Journals Online (AJOL)

    Nigerian Endocrine Practice ... of interventional studies should be systolic 130 – 135 mm Hg and diastolic BP not below 70mm Hg. There are increased risks when systolic BP is higher than 140 mm Hg. Combination therapy which should include initially an RAAS (Renin Angiotensin Aldosterone System) blocker is required.

  10. The impact of age and gender on reporting of cough and angioedema with RAS inhibitors: A case/non-case in VigiBase

    NARCIS (Netherlands)

    Alharbi, Fawaz F.; Kholod, Anzhelika A.V.; Souverein, Patrick C.; Meyboom, Ron H.; de Groot, Mark; De Boer, Anthonius; Klungel, Olaf H.

    2016-01-01

    Background: Little is known about the effect of age and gender on reporting of cough/ angioedema with renin angiotensin system (RAS) inhibitors (angiotensin- converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and aliskiren, a direct renin inhibitor (DRI). Objectives: To assess

  11. Does ACE inhibition limit structural changes in the heart following myocardial infarction?

    NARCIS (Netherlands)

    Smits, J. F.; Passier, R. C.; Nelissen-Vrancken, H. J.; Cleutjens, J. P.; Kuizinga, M. C.; Daemen, M. J.

    1995-01-01

    A recent series of experiments in our laboratory were designed to elucidate the cellular changes that underlie the cardiac remodelling response following myocardial infarction (MI) in the rat as well as the potential role of the renin-angiotensin system (RAS) in this response. Inhibition of the RAS

  12. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials

    DEFF Research Database (Denmark)

    Chaturvedi, N.; Porta, M.; Klein, R.

    2008-01-01

    BACKGROUND: Results of previous studies suggest that renin-angiotensin system blockers might reduce the burden of diabetic retinopathy. We therefore designed the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme to assess whether candesartan could reduce the incidence and progression of ...... of retinopathy, we did not see a beneficial effect on retinopathy progression Udgivelsesdato: 2008/10/18...

  13. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials

    DEFF Research Database (Denmark)

    Chaturvedi, Nish; Porta, Massimo; Klein, Ronald

    2008-01-01

    BACKGROUND: Results of previous studies suggest that renin-angiotensin system blockers might reduce the burden of diabetic retinopathy. We therefore designed the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme to assess whether candesartan could reduce the incidence and progression of ...... of retinopathy, we did not see a beneficial effect on retinopathy progression....

  14. Frontiers in Research

    DEFF Research Database (Denmark)

    Sumners, Colin; Horiuchi, Masatsugu; Widdop, Robert E

    2013-01-01

    In recent years it has been firmly established that apart from the classical renin-angiotensin-system (RAS) comprising angiotensin II (Ang II), angiotensin converting enzyme (ACE) - being responsible for Ang II generation - and the angiotensin type 1 receptor (AT1R), there also exist protective a...

  15. Telmisartan to prevent recurrent stroke and cardiovascular events

    NARCIS (Netherlands)

    Yusuf, Salim; Diener, Hans-Christoph; Sacco, Ralph L.; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A.; Palesch, Yuko; Martin, Renee H.; Albers, Gregory W.; Bath, Philip; Bornstein, Natan; Chan, Bernard P. L.; Chen, Sien-Tsong; Cunha, Luis; Dahlof, Bjorn; de Keyser, Jacques; Donnan, Geoffrey A.; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

    2008-01-01

    Background: Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood

  16. Response to angiotensin-converting enzyme inhibition is selectively blunted by high sodium in angiotensin-converting enzyme DD genotype : Evidence for gene-environment interaction in healthy volunteers

    NARCIS (Netherlands)

    Lely, A. Titia; Lambers Heerspink, Hiddo J.; Zuurman, Mike; Visser, Folkert W.; Kocks, Menno J. A.; Boomsma, Frans; Navis, Gerjan

    2010-01-01

    Background Renin-angiotensin-aldosterone system blockade is a cornerstone in cardiovascular protection. Angiotensin-converting enzyme (ACE)-DD genotype has been associated with resistance to angiotensin-converting enzyme inhibition (ACEi), but data are conflicting. As sodium intake modifies the

  17. Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy : A Randomized Clinical Trial

    NARCIS (Netherlands)

    Bakris, George L; Agarwal, Rajiv; Chan, Juliana C; Cooper, Mark E; Gansevoort, Ron T; Haller, Hermann; Remuzzi, Giuseppe; Rossing, Peter; Schmieder, Roland E; Nowack, Christina; Kolkhof, Peter; Joseph, Amer; Pieper, Alexander; Kimmeskamp-Kirschbaum, Nina; Ruilope, Luis M

    2015-01-01

    IMPORTANCE: Steroidal mineralocorticoid receptor antagonists, when added to a renin-angiotensin system blocker, further reduce proteinuria in patients with chronic kidney disease but may be underused because of a high risk of adverse events. OBJECTIVE: To evaluate the safety and efficacy of

  18. ACACβ gene (rs2268388) and AGTR1 gene (rs5186) polymorphism and the risk of nephropathy in Asian Indian patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Shah, Viral N; Cheema, Balneek Singh; Sharma, Rajni

    2013-01-01

    Patients with type 2 diabetes (T2DM) are usually obese and concurrent obesity results into activation of the renin-angiotensin-system (RAS) which is a risk factor for diabetic nephropathy (DN). Gene-gene interaction between acetyl-coenzymeA carboxylase beta (ACACβ) gene, which is involved in fatt...

  19. Renal renin secretion as regulator of body fluid homeostasis

    DEFF Research Database (Denmark)

    Damkjær, Mads; Isaksson, Gustaf L; Stubbe, Jane

    2013-01-01

    The renin-angiotensin system is essential for body fluid homeostasis and blood pressure regulation. This review focuses on the homeostatic regulation of the secretion of active renin in the kidney, primarily in humans. Under physiological conditions, renin secretion is determined mainly by sodium...

  20. CARDIOVASCULAR ENDOCRINOLOGY Dual RAAS blockade has dual effects on outcome

    NARCIS (Netherlands)

    Heerspink, Hiddo J. Lambers; de Zeeuw, Dick

    Makani and colleagues report that dual blockade of the renin-angiotensin-aldosterone system is associated with harm despite previous studies showing that this approach decreases blood pressure and albuminuria. Do these results imply that we should abandon surrogate markers? Or should we become more

  1. Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression

    DEFF Research Database (Denmark)

    Dhamrait, Sukhbir S.; Maubaret, Cecilia; Pedersen-Bjergaard, Ulrik

    2016-01-01

    Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial...

  2. Epoxyeicosatrienoic acid analog attenuates the development of malignant hypertension, but does not reverse it once established: a study in Cyp1a1-Ren-2 transgenic rats

    Czech Academy of Sciences Publication Activity Database

    Jíchová, Š.; Kopkan, L.; Husková, Z.; Doleželová, Š.; Neckář, Jan; Kujal, P.; Vernerová, Z.; Kramer, H. J.; Sadowski, J.; Kompanowska; Jezierska, E.; Reddy, N. R.; Falck, J. R.; Imig, J. D.; Červenka, L.

    2016-01-01

    Roč. 34, č. 10 (2016), s. 2008-2025 ISSN 0263-6352 R&D Projects: GA ČR(CZ) GA15-07544S Institutional support: RVO:67985823 Keywords : epoxyeicosatrienoic acid analog * malignant hypertension * renal blood flow autoregulation * renin-angiotensin system * sodium excretion Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.085, year: 2016

  3. Chronic blockade of angiotensin II action prevents glomerulosclerosis, but induces graft vasculopathy in experimental kidney transplantation

    NARCIS (Netherlands)

    Smit-van Oosten, A; Navis, G; Stegeman, CA; Joles, JA; Klok, PA; Kuipers, F; Tiebosch, ATMG; van Goor, H

    Long-term renin-angiotensin system blockade is beneficial in a variety of renal diseases, This study examines the long-term (34 weeks) effects of the angiotensin-converting enzyme inhibitor lisinopril and the angiotensin II receptor type I blocker L158,809 in the Fisher to Lewis rat model of chronic

  4. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Kristensen, Karl Emil; Torp-Pedersen, Christian; Gislason, Gunnar Hilmar

    2015-01-01

    OBJECTIVE: The renin-angiotensin system is thought to play a pivotal role in the pathogenesis of abdominal aortic aneurysms (AAAs). However, effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) on human AAAs remain unclear. We therefore ex...

  5. Elevated N-terminal pro-brain natriuretic peptide levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of dietary sodium restriction and diuretics, but not angiotensin receptor blockade, in proteinuric renal patients

    NARCIS (Netherlands)

    Slagman, Maartje C. J.; Waanders, Femke; Vogt, Liffert; Damman, Kevin; Hemmelder, Marc; Navis, Gerjan; Laverman, Gozewijn D.

    2012-01-01

    Background. Renin angiotensin aldosterone system (RAAS) blockade only partly reduces blood pressure, proteinuria and renal and cardiovascular risk in chronic kidney disease (CKD) but often requires sodium targeting [i.e. low sodium diet (LS) and/or diuretics] for optimal efficacy. However, both

  6. Elevated N-terminal pro-brain natriuretic peptide levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of dietary sodium restriction and diuretics, but not angiotensin receptor blockade, in proteinuric renal patients

    NARCIS (Netherlands)

    Slagman, Maartje C. J.; Waanders, Femke; Vogt, Liffert; Damman, Kevin; Hemmelder, Marc; Navis, Gerjan; Laverman, Gozewijn D.

    Background. Renin angiotensin aldosterone system (RAAS) blockade only partly reduces blood pressure, proteinuria and renal and cardiovascular risk in chronic kidney disease (CKD) but often requires sodium targeting [i.e. low sodium diet (LS) and/or diuretics] for optimal efficacy. However, both

  7. Tolerance to Central Hypovolemia: The Influence of Oscillations in Arterial Pressure and Cerebral Blood Velocity

    Science.gov (United States)

    2011-10-01

    investigated. This oscillatory response to hypovolemia has been exten- sively reported. In 1951 Guyton and Harris (27) observed a distinctive...the renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol 279: R822–R829, 2000. 27. Guyton AC, Harris JW. Pressoreceptor-autonomic

  8. Cardiovascular, endocrine, and renal effects of urodilatin in normal humans

    DEFF Research Database (Denmark)

    Bestle, M H; Olsen, Niels Vidiendal; Christensen, P

    1999-01-01

    highest doses. The renin-angiotensin-aldosterone system was inhibited by the three lowest doses but activated by the hypotensive dose of 40 ng. kg-1. min-1. Plasma vasopressin increased by factors of up to 5 during infusion of the three highest doses. Atrial natriuretic peptide immunoreactivity (including...

  9. Feasibility of combined treatment with enalapril and candesartan in advanced chronic kidney disease

    DEFF Research Database (Denmark)

    Frimodt-Møller, Marie; Høj Nielsen, Arne; Strandgaard, Svend

    2010-01-01

    BACKGROUND: Dual blockade of the renin-angiotensin system (RAS) has been claimed to have a specific renal protective effect in chronic kidney disease (CKD). The present short-term study reports on the feasibility of dual blockade in a consecutive group of patients with CKD stage 3-5. METHODS: Forty...

  10. Ularitide/ Omapatrilat in Congestive Heart Failure

    African Journals Online (AJOL)

    Aim: This study aimed to address the effect of ularitide and OMA in aortocaval fistula (ACF) – induced congestive heart failure (CHF) in rats under various conditions of compensation (of ... Keywords: Congestive heart failure; Aorto-caval fistula; Ularitide; Omapatrilat; Renin-angiotensin system; Vasopeptidase inhibition ...

  11. Selective Activation of At2 Receptor Attenuates Progression of Pulmonary Hypertension and Inhibits Cardiopulmonary Fibrosis

    DEFF Research Database (Denmark)

    Bruce, E; Shenoy, V; Rathinasabapathy, A

    2015-01-01

    BACKGROUND AND PURPOSE: Pulmonary hypertension (PH) is a devastating disease characterized by increased pulmonary arterial pressure, which progressively leads to right heart failure and death. A dysregulated renin angiotensin system (RAS) has been implicated in the development and progression of PH...

  12. [Hypertension and renal disease

    DEFF Research Database (Denmark)

    Kamper, A.L.; Pedersen, E.B.; Strandgaard, S.

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...

  13. Hypertension og nyresygdom

    DEFF Research Database (Denmark)

    Kamper, Anne-Lise; Pedersen, Erling B; Strandgaard, Svend

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...

  14. Effects of sodium restriction and hydrochlorothiazide on RAAS blockade efficacy in diabetic nephropathy : a randomised clinical trial

    NARCIS (Netherlands)

    Kwakernaak, Arjan J.; Krikken, Jan A.; Binnenmars, S. Heleen; Visser, Folkert W.; Hemmelder, Marc H.; Woittiez, Arend-Jan; Groen, Henk; Laverman, Gozewijn D.; Navis, Gerjan

    Background Reduction of dietary sodium intake or diuretic treatment increases renin-angiotensin-aldosterone system (RAAS) blockade efficacy in non-diabetic nephropathy. We aimed to investigate the effect of sodium restriction and the diuretic hydrochlorothiazide, separately and in combination, added

  15. Lupus nephritis: An approach to diagnosis and treatment in South ...

    African Journals Online (AJOL)

    1. Month 20xx, Vol. xxx, No. x. Definition and epidemiology of lupus nephritis ... In all patients, treatment should include adjunctive therapies such as renin angiotensin aldosterone system blockade, bone protection .... Glucose intolerance/diabetes mellitus, osteoporosis, hypertension, gastritis, cataracts, avascular necrosis of ...

  16. Plasma Vitamin D Level and Change in Albuminuria eGFR According to Sodium Intake

    NARCIS (Netherlands)

    Keyzer, Charlotte A; Lambers-Heerspink, Hiddo J; Joosten, Michel M; Deetman, Petronella E; Gansevoort, Ron T; Navis, Gerjan; Kema, Ido P; de Zeeuw, Dick; Bakker, Stephan J L; de Borst, Martin H

    2015-01-01

    Background and objectives Low circulating 25-hydroxyvitamin D [25(OH)D] and high sodium intake are both associated with progressive albuminuria and renal function loss in CKD. Both vitamin D and sodium intake interact with the renin-angiotensin-aldosterone system. We investigated whether plasma

  17. Structural characteristics and antihypertensive effects of angiotensin ...

    African Journals Online (AJOL)

    Structural characteristics and antihypertensive effects of angiotensin-iconverting enzyme inhibitory peptides in the renin-angiotensin and kallikrein kinin systems. ... Background: The commercially available synthetic angiotensin-I-converting enzyme (ACE) inhibitors are known to exert negative side effects which have driven ...

  18. Effect of the renal natriuretic peptide, ularitide, alone or combined ...

    African Journals Online (AJOL)

    Rehab E. Abo El gheit

    2016-06-11

    Jun 11, 2016 ... Renal outcome was measured by glomerular filtration rate (GFR), fractional excretion of sodium. (FNa), absolute urinary ... activation of renin angiotensin aldosterone system (RAAS), elevated ANP with renal resistance to ANP ...... secretory reserve of NPs associated with the decompensated. HF.39 This ...

  19. Blockade of AT1 receptors by losartan did not affect renin gene expression in kidney medulla

    Czech Academy of Sciences Publication Activity Database

    Tybitanclová, K.; Szabová, L.; Grima, M.; Ingert, C.; Železná, Blanka; Zórad, Š.

    2006-01-01

    Roč. 25, č. 1 (2006), s. 43-51 ISSN 0231-5882 Grant - others:VEGA(SK) 2/5090/25 Institutional research plan: CEZ:AV0Z50520514 Keywords : AT1 receptor * renin-angiotensin system * kidney s Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.771, year: 2006

  20. [Characteristics of central nervous system activity in patients with complications of arterial hypertension and dependence on psychomotor status and treatment].

    Science.gov (United States)

    Usenko, A G; Velichko, N P; Usenko, G A; Nishcheta, O V; Kozyreva, T Iu; Demin, A A

    2013-01-01

    Changes in certain CNS characteristics were used as indicators of the efficacy of antihypertensive therapy (AHT) both targeted (T-AHT) and empirical (E-AHT) designed to suppress activity of the sympathetic component of vegetative nervous system (VNS) and renin-angiotensin-aldosterone system (RAAS) in patients of different psychic status and AH. A group of 835 men (mean age 54.2+-1.8yr) was divided into cholerics, sanguinics, melancholics and phlegmatics with a high and low anxiety level (HA and LA). 416 healthy men served as controls. The following parameters were estimated: mobility of cortical processes, balance between sympathetic and parasympathetic activities, blood corrisol and aldosterone levels, oxygen utilization coefficient, resistance to breath holding, severity of dyscirculatory encephalopathy and the fraction of patients with AH complications during 12 month T-AHT for the suppression of sympathetic activity in cholerics and sanguinics by beta-adrenoblockers and PAA C- ACE inhibitors in phlegmatics and melancholics and during E-AHT (ACE inhibitors in cholerics and sanguinics, BAB in phlegmatics and melancholics). The functional activity of CNS in phlegmatics and melancholics before and during AHT was lower and severity of encephalopathy and the number ofAH complications higher than in cholerics and sanguinics. . The changes wiere more pronounced in patients with HA than in those with LA. Unlike E-AHT T-AHT (anxiolytics for cholerics and sanguinics with HA, antidepressants for phlegmatics and melancholics with HA) normalized the study parameters and decreased the frequency of complications by 2-3 times.

  1. Targeting the Renin–Angiotensin System Combined With an Antioxidant Is Highly Effective in Mitigating Radiation-Induced Lung Damage

    Energy Technology Data Exchange (ETDEWEB)

    Mahmood, Javed [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Jelveh, Salomeh [Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Zaidi, Asif [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Doctrow, Susan R. [Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts (United States); Medhora, Meetha [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Hill, Richard P., E-mail: hill@uhnres.utoronto.ca [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Toronto, Ontario (Canada)

    2014-07-15

    Purpose: To investigate the outcome of suppression of the renin angiotensin system using captopril combined with an antioxidant (Eukarion [EUK]-207) for mitigation of radiation-induced lung damage in rats. Methods and Materials: The thoracic cavity of female Sprague-Dawley rats was irradiated with a single dose of 11 Gy. Treatment with captopril at a dose of 40 mg/kg/d in drinking water and EUK-207 given by subcutaneous injection (8 mg/kg daily) was started 1 week after irradiation (PI) and continuing until 14 weeks PI. Breathing rate was monitored until the rats were killed at 32 weeks PI, when lung fibrosis was assessed by lung hydroxyproline content. Lung levels of the cytokine transforming growth factor-β1 and macrophage activation were analyzed by immunohistochemistry. Oxidative DNA damage was assessed by 8-hydroxy-2-deoxyguanosine levels, and lipid peroxidation was measured by a T-BARS assay. Results: The increase in breathing rate in the irradiated rats was significantly reduced by the drug treatments. The drug treatment also significantly decreased the hydroxyproline content, 8-hydroxy-2-deoxyguanosine and malondialdehyde levels, and levels of activated macrophages and the cytokine transforming growth factor-β1 at 32 weeks. Almost complete mitigation of these radiation effects was observed by combining captopril and EUK-207. Conclusion: Captopril and EUK-207 can provide mitigation of radiation-induced lung damage out to at least 32 weeks PI after treatment given 1-14 weeks PI. Overall the combination of captopril and EUK-207 was more effective than the individual drugs used alone.

  2. Resveratrol inhibits the intracellular calcium increase and angiotensin/endothelin system activation induced by soluble uric acid in mesangial cells

    Directory of Open Access Journals (Sweden)

    G. Albertoni

    2015-01-01

    Full Text Available Resveratrol (Resv is natural polyphenol found in grapes. This study evaluated the protective effect of Resv against the effects of uric acid (UA in immortalized human mesangial cells (ihMCs. ihMCs were preincubated with Resv (12.5 µM for 1 h and treated with UA (10 mg/dL for 6 or 12 h. The intracellular calcium concentration [Ca2+]i was quantified by fluorescence using flow cytometry. Angiotensinogen (AGT and pre-pro endothelin-1 (ppET-1 mRNA were assayed by quantitative real-time RT-PCR. Angiotensin II (AII and endothelin-1 (ET-1 were assayed by ELISA. UA significantly increased [Ca2+]i. Pre-incubation with Resv significantly reduced the change in [Ca2+]i induced by UA. Incubation with UA for 6 or 12 h also increased AGT mRNA expression and AII protein synthesis. Resv blunted these increases in AGT mRNA expression and AII protein. Incubation with UA in the ihMCs increased ppET-1 expression and ET-1 protein synthesis at 6 and 12 h. When ihMCs were pre-incubated with Resv, UA had a significantly diminished effect on ppET-1 mRNA expression and ET-1 protein synthesis at 6 and 12 h, respectively. Our results suggested that UA triggers reactions including AII and ET-1 production in mesangial cells. The renin-angiotensin system may contribute to the pathogenesis of renal function and chronic kidney disease. Resv can minimize the impact of UA on AII, ET-1 and the increase of [Ca2+]i in mesangial cells, suggesting that, at least in part, Resv can prevent the effects of soluble UA in mesangial cells.

  3. Resveratrol inhibits the intracellular calcium increase and angiotensin/endothelin system activation induced by soluble uric acid in mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Albertoni, G.; Schor, N. [Divisão de Nefrologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-10-24

    Resveratrol (Resv) is natural polyphenol found in grapes. This study evaluated the protective effect of Resv against the effects of uric acid (UA) in immortalized human mesangial cells (ihMCs). ihMCs were preincubated with Resv (12.5 µM) for 1 h and treated with UA (10 mg/dL) for 6 or 12 h. The intracellular calcium concentration [Ca{sup 2+}]i was quantified by fluorescence using flow cytometry. Angiotensinogen (AGT) and pre-pro endothelin-1 (ppET-1) mRNA were assayed by quantitative real-time RT-PCR. Angiotensin II (AII) and endothelin-1 (ET-1) were assayed by ELISA. UA significantly increased [Ca{sup 2+}]i. Pre-incubation with Resv significantly reduced the change in [Ca{sup 2+}]i induced by UA. Incubation with UA for 6 or 12 h also increased AGT mRNA expression and AII protein synthesis. Resv blunted these increases in AGT mRNA expression and AII protein. Incubation with UA in the ihMCs increased ppET-1 expression and ET-1 protein synthesis at 6 and 12 h. When ihMCs were pre-incubated with Resv, UA had a significantly diminished effect on ppET-1 mRNA expression and ET-1 protein synthesis at 6 and 12 h, respectively. Our results suggested that UA triggers reactions including AII and ET-1 production in mesangial cells. The renin-angiotensin system may contribute to the pathogenesis of renal function and chronic kidney disease. Resv can minimize the impact of UA on AII, ET-1 and the increase of [Ca{sup 2+}]i in mesangial cells, suggesting that, at least in part, Resv can prevent the effects of soluble UA in mesangial cells.

  4. Role of angiotensin II and endothelin-1 receptors in aging-related functional changes in rat cardiovascular system.

    Science.gov (United States)

    Ishihata, Akira; Katano, Yumi

    2006-05-01

    Angiotensin II (AII) and endothelin-1 (ET-1) are regarded as key players in the age-related changes in cardiovascular function. They are known to be involved in the pathogenesis of cardiac fibrosis and coronary vascular atherosclerosis. AII- and ET-induced vasoconstriction was augmented in coronary arteries of Langendorff-perfused heart from aged rats. In papillary muscles, ET-1-induced positive inotropic effect (PIE) was diminished by aging. On the other hand, both ET-1 and AII caused greater vasoconstriction in aged rat coronary arteries compared to those in the young rat. To further elucidate the mechanism of these age-dependent changes in cardiovascular effects of ET-1 and AII, we examined the expression of AII and ET-1 receptors in young (2-month-old) and aged (24-month-old) rats. Total RNA was isolated from left ventricles. For determination of the gene expression of AT(1) receptor and ET(A)/ET(B) receptor mRNA, competitive RT-PCR and Northern blot analysis were performed, respectively. [(125)I]ET-1 receptor assay was carried out in left ventricular membrane fraction. AT(1)-receptor, ET(A)-, and ET(B)-receptor mRNA were upregulated in the left ventricles of senescent rats compared with young ones. The affinity of ET-1-receptor was not changed, but receptor density was significantly increased in aged rats. Although the precise mechanism for the upregulation of AT(1) receptor and ET-1 receptor in the aged rat heart has not been clarified yet, these findings suggest that the activation of the renin-angiotensin system as well as ET receptor may be important for the physiological changes in aged hearts.

  5. Which Should be Preferred for Moderate-Size Kidney Stones? Ultramini Percutaneous Nephrolithotomy or Retrograde Intrarenal Surgery?

    Science.gov (United States)

    Demirbas, Arif; Resorlu, Berkan; Sunay, Mehmet Melih; Karakan, Tolga; Karagöz, Mehmet Ali; Doluoglu, Omer Gokhan

    2016-12-01

    Comparison of effectiveness and safety of ultramini percutaneous nephrolithotomy (UMPNL) and retrograde intrarenal surgery (RIRS) in treatment of moderate-sized renal stones. The patients scheduled for surgery attributable to renal stones with the greatest diameter of 10 to 25 mm were prospectively analyzed. Patients were randomized into groups with tossing a coin method. The patients who had UMPNL and RIRS were defined as Group I and Group II, respectively. The groups were compared for demograhic data, stone characteristics, operative and postoperative data, stone-free status, and the complications. Student's t-test and Pearson's Chi square tests were used for statistical analysis. p stone, and surface area characteristics of the stone (p = 0.194, p = 0.470, p = 0.990, and p = 0.487, respectively). Stone-free rate was 80% (n = 24) in UMPNL, and 74.4% (n = 32) in RIRS (p = 0.579). Modified Clavien Classification Grade 1 to 2 and 3A to 3B complications were similar in two groups (p = 0.959 and p = 0.192, respectively). Comparison of stone-free rates was 93.3% in UMPNL, and 42.9% in RIRS groups for lower pole stones (p = 0.009). Groups I and II were significantly different for visual analog scale scores for postoperative pain (4.73 ± 1.25 vs 2.30 ± 1.12), hospital stay (2.46 ± 3.02 vs 1.37 ± 1.48 days), and time to return to normal daily life (11.26 ± 5.55 vs 6.65 ± 4.30 days) (p stones. However, UMPNL is more effective than RIRS in treatment of lower pole stones. RIRS is more advantageous when loss from work is taken into consideration.

  6. Captopril and Valsartan May Improve Cogniti ve Function Through Potentiation of the Brain Antioxidant Defense System and Attenuation of Oxidative/Nitrosative Damage in STZ - Induced Dementia in Rat

    Directory of Open Access Journals (Sweden)

    Yasaman Arjmand Abbassi

    2016-12-01

    Full Text Available Purpose: Previous findings have shown the crucial roles of brain renin-angiotensin system (RAS in pathogenesis of Alzheimer’s disease (AD. Since RAS inhibitors may have beneficial effects on dementia and cognitive function in elderly people, the aim of present study was to examine the neuroprotective actions of captopril and valsartan on memory function and neuronal damage in experimental model of AD. Methods: Adult forty male Wistar rats (220-280g were randomly divided into 5 groups; Control, Vehicle, Alzheimer and treatment groups. AD was induced by the injections of streptozotocin (3mg/kg, bilateral intracerebroventricular at days 1&3. Treated rats received orally captopril (50mg/kg/day and valsartan (30mg/kg/day. Memory function and histological assessments were done at termination of experiment. Finally, superoxide dismutase (SOD and catalase (CAT activities as well as malondialdehyde (MDA and NOx contents were determined. Results: There was a significant increase in the mean value of latency in Alzheimer group (66%. Captopril and valsartan considerably decreased this value in both treatment groups (45% and 72%, respectively. In Alzheimer group the activities of brain’s SOD and CAT reduced (40% and 47%, respectively in accompany with an increase in MDA and NOx contents (49% and 50%, respectively. Captopril and valsartan significantly increased the activities of brain’s SOD and CAT concomitant reduction in MDA and NOx contents. Also, histopathological damages noticeably decreased in both treatment groups. Conclusion: Our findings indicate that RAS inhibition by using captopril and valsartan potentiates the antioxidant defense system of brain and reduces oxidative/nitrosative stress in accompany with neuronal damage during AD.

  7. Extracorporeal shock wave lithotripsy (ESWL) versus percutaneous nephrolithotomy (PCNL) or retrograde intrarenal surgery (RIRS) for kidney stones.

    Science.gov (United States)

    Srisubat, Attasit; Potisat, Somkiat; Lojanapiwat, Bannakij; Setthawong, Vasun; Laopaiboon, Malinee

    2014-11-24

    Stones in the urinary tract are a common medical problem in the general population. At present, the great expansion in minimally invasive techniques has led to the decrease in open surgery. Extracorporeal shock wave lithotripsy (ESWL) has been introduced as an alternative approach which disintegrates stones in the kidney and upper urinary tract through the use of shock waves. Nevertheless, as there are limitations with the success rate in ESWL, other minimally invasive modalities for kidney stones such as percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) are also widely applied. This is an update of a review first published in 2009. This review aimed to assess the effectiveness and complications of ESWL for kidney stones compared with PCNL or RIRS. We searched the Cochrane Renal Group's Specialised Register to 3 March 2014 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Randomised controlled trials (RCTs) assessing the use of ESWL compared to PCNL or RIRS for kidney stone management. Two authors independently assessed all the studies for inclusion. Statistical analyses were performed using the random effects model and the results expressed as risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous data with 95% confidence intervals (CI). Five studies (338 patients) were included, four studies compared ESWL to PCNL and one compared ESWL with RIRS. Random sequence generation was reported in three studies and unclear in two. Allocation concealment was not reported in any of the included studies. Blinding of participants and investigators could not be undertaken due to the nature of the interventions; blinding of outcome assessors was not reported. Reporting bias was judged to be low risk in all studies. One study was funded by industry and in one study the number of participants in each group was unbalanced.The success of treatment at three months was significantly

  8. Comparison between retrograde intrarenal surgery and extracorporeal shock wave lithotripsy in the treatment of lower pole kidney stones up to 15 mm. Prospective, randomized study.

    Science.gov (United States)

    Vilches, R M; Aliaga, A; Reyes, D; Sepulveda, F; Mercado, A; Moya, F; Ledezma, R; Hidalgo, J P; Olmedo, T; Marchant, F

    2015-05-01

    Extracorporeal Shock Wave Lithotripsy (ESWL) is currently the recommended treatment for intra-renal calculi smaller than 2 cm. However the low Stone Free Rate (SFR) in lower pole calculi gives rise to new techniques, such us retrograde intrarenal surgery (RIRS), for improve the surgery outcomes. To compare the efficacy of a treatment with ESWL with RIRS, in terms of SFR after surgery, in patients with kidney stones up to 15 mm in the lower pole. A prospective study was carried out in order to assess the results of ESWL and RIRS in patients with lower pole stones less than 15 mm. Among a total of 55 patients, 31 were underwent to ESWL (Group 1) and the remaining 24 to RIRS (Group 2). Clinical data recorded, including general characteristics of each patient, were: calculi size, side, operative time, complications according to Clavien scale, SFR and the presence of residual fragments at 2 months post-treatment assessed by a CT scan. STATA 11 was used to perform the statistical analysis. There were no differences for general descriptors among groups with the exception of a significantly longer operative time for RIRS. The rates of SFR and residual fragments lesser than 3 mm. were lower in the RIRS group than in ESWL ones. RIRS also showed a lower rate of clinically significant fragments (0% vs 42.3%. P stones between 10/15 mm RIRS showed higher SFR (75% vs. 41.2%) and a lower rate of stones>3 mm (0% vs. 58.8%), being statistically significant (P stone RIRS has the same results than ESWL in terms of SFR. Regarding absence of a clinically significant residual fragment, RIRS was superior to ESWL. A bigger sample size is required in order to confirm this results. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. CYP epoxygenase-derived H2O2 is involved in the endothelium-derived hyperpolarization (EDH) and relaxation of intrarenal arteries.

    Science.gov (United States)

    Muñoz, Mercedes; López-Oliva, Maria Elvira; Pinilla, Estéfano; Martínez, María Pilar; Sánchez, Ana; Rodríguez, Claudia; García-Sacristán, Albino; Hernández, Medardo; Rivera, Luis; Prieto, Dolores

    2017-05-01

    Reactive oxygen species (ROS) like hydrogen peroxide (H 2 O 2 ) are involved in the in endothelium-derived hyperpolarization (EDH)-type relaxant responses of coronary and mesenteric arterioles. The role of ROS in kidney vascular function has mainly been investigated in the context of harmful ROS generation associated to kidney disease. The present study was sought to investigate whether H 2 O 2 is involved in the endothelium-dependent relaxations of intrarenal arteries as well the possible endothelial sources of ROS generation involved in these responses. Under conditions of cyclooxygenase (COX) and nitric oxide (NO) synthase inhibition, acetylcholine (ACh) induced relaxations and stimulated H 2 O 2 release that were reduced by catalase and by the glutathione peroxidase (GPx) mimetic ebselen in rat renal interlobar arteries, suggesting the involvement of H 2 O 2 in the endothelium-dependent responses. ACh relaxations were also blunted by the CYP2C inhibitor sulfaphenazole and by the NADPH oxidase inhibitor apocynin. Acetylcholine stimulated both superoxide (O 2 •- ) and H 2 O 2 production that were reduced by sulfaphenazole and apocynin. Expression of the antioxidant enzyme CuZnSOD and of the H 2 O 2 reducing enzymes catalase and GPx-1 was found in both intrarenal arteries and renal cortex. On the other hand, exogenous H 2 O 2 relaxed renal arteries by decreasing vascular smooth muscle (VSM) intracellular calcium concentration [Ca 2+ ] i and markedly enhanced endothelial K Ca currents in freshly isolated renal endothelial cells. CYP2C11 and CYP2C23 epoxygenases were highly expressed in interlobar renal arteries and renal cortex, respectively, and were co-localized with eNOS in renal endothelial cells. These results demonstrate that H 2 O 2 is involved in the EDH-type relaxant responses of renal arteries and that CYP 2C epoxygenases are physiologically relevant endothelial sources of vasodilator H 2 O 2 in the kidney. Copyright © 2017 Elsevier Inc. All rights

  10. Improvement in renal hemodynamics following combined angiotensin II infusion and AT1R blockade in aged female sheep following fetal unilateral nephrectomy.

    Directory of Open Access Journals (Sweden)

    Reetu R Singh

    Full Text Available Renin-angiotensin system (RAS is a powerful modulator of renal hemodynamic and fluid homeostasis. Up-regulation in components of intra-renal RAS occurs with ageing. Recently we reported that 2 year old uninephrectomised (uni-x female sheep have low renin hypertension and reduced renal function. By 5 years of age, these uni-x sheep had augmented decrease in renal blood flow (RBF compared to sham. We hypothesised that this decrease in RBF in 5 year old uni-x sheep was due to an up-regulation in components of the intra-renal RAS. In this study, renal responses to angiotensin II (AngII infusion and AngII type 1 receptor (AT1R blockade were examined in the same 5 year old sheep. We also administered AngII in the presence of losartan to increase AngII bioavailability to the AT2R in order to understand AT2R contribution to renal function in this model. Uni-x animals had significantly lower renal cortical content of renin, AngII (∼40% and Ang 1-7 (∼60% and reduced cortical expression of AT1R gene than sham animals. In response to both AngII infusion and AT1R blockade via losartan, renal hemodynamic responses and tubular sodium excretion were significantly attenuated in uni-x animals compared to sham. However, AngII infusion in the presence of losartan caused ∼33% increase in RBF in uni-x sheep compared to ∼14% in sham (P<0.05. This was associated with a significant decrease in renal vascular resistance in the uni-x animals (22% vs 15%, P<0.05 without any changes in systemic blood pressure. The present study shows that majority of the intra-renal RAS components are suppressed in this model of low renin hypertension. However, increasing the availability of AngII to AT2R by AT1R blockade improved renal blood flow in uni-x sheep. This suggests that manipulation of the AT2R maybe a potential therapeutic target for treatment of renal dysfunction associated with a congenital nephron deficit.

  11. Improvement in renal hemodynamics following combined angiotensin II infusion and AT1R blockade in aged female sheep following fetal unilateral nephrectomy.

    Science.gov (United States)

    Singh, Reetu R; Lankadeva, Yugeesh R; Denton, Kate M; Moritz, Karen M

    2013-01-01

    Renin-angiotensin system (RAS) is a powerful modulator of renal hemodynamic and fluid homeostasis. Up-regulation in components of intra-renal RAS occurs with ageing. Recently we reported that 2 year old uninephrectomised (uni-x) female sheep have low renin hypertension and reduced renal function. By 5 years of age, these uni-x sheep had augmented decrease in renal blood flow (RBF) compared to sham. We hypothesised that this decrease in RBF in 5 year old uni-x sheep was due to an up-regulation in components of the intra-renal RAS. In this study, renal responses to angiotensin II (AngII) infusion and AngII type 1 receptor (AT1R) blockade were examined in the same 5 year old sheep. We also administered AngII in the presence of losartan to increase AngII bioavailability to the AT2R in order to understand AT2R contribution to renal function in this model. Uni-x animals had significantly lower renal cortical content of renin, AngII (∼40%) and Ang 1-7 (∼60%) and reduced cortical expression of AT1R gene than sham animals. In response to both AngII infusion and AT1R blockade via losartan, renal hemodynamic responses and tubular sodium excretion were significantly attenuated in uni-x animals compared to sham. However, AngII infusion in the presence of losartan caused ∼33% increase in RBF in uni-x sheep compared to ∼14% in sham (Pblood pressure. The present study shows that majority of the intra-renal RAS components are suppressed in this model of low renin hypertension. However, increasing the availability of AngII to AT2R by AT1R blockade improved renal blood flow in uni-x sheep. This suggests that manipulation of the AT2R maybe a potential therapeutic target for treatment of renal dysfunction associated with a congenital nephron deficit.

  12. Visualization of the renal venous system by renal arteriography with digital subtraction angiography

    International Nuclear Information System (INIS)

    Nagai, Jun

    1989-01-01

    The purpose of this study was to obtain vivid and precise images of intrarenal venous branching using DSA for renal arteriography. The type of system used was an ADAC DPS-4100C with 70-80 kVp, and 320 mA, 25-50 msec at 6 frames/sec. The duration was 10 sec and the matrix size was 512x512. In order to retain clear subtracted images of intrarenal venous branching with minimal noise the three frames were selected on the time-density curve of DSA: (Fig.3). 1) a frame on which renal arteries disappear (frame X), 2) the frame with highest renal venous density value as (frame Y), 3) the difference of the nephrogram density between X and Y frames in which only the density of the nephrogram decreases (frame Z). The mask image is the image subtracted by the equation of the weighted averaging method on X and Z frame and is subtracted from the image of Y frame in the final step. By this method, 40 kidneys in 36 patients were studied, and the intrarenal venous branches up to the interlobar vein was clearly demonstrated in 28 of these cases (70%). This method is useful to estimate the extent of intrarenal lesions and detect abnormal renal blood flow compared with conventional temporal subtraction method. (author)

  13. Expression and activity of angiotensin-regulating enzymes is associated with prognostic outcome in clear cell renal cell carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Peio Errarte

    Full Text Available The discovery of the intrarenal renin-angiotensin system (iRAS, which regulates angiogenesis, cell differentiation and proliferation, has opened new perspectives in the knowledge of kidney carcinogenesis. In this study we analyzed the immunohistochemical expression and fluorimetric activity of four key peptidases of iRAS in tumor tissue (n = 144 and serum samples (n = 128 from patients with renal neoplasms. Neutral endopeptidase (NEP/CD10, Angiotensin-converting enzyme-2 (ACE2, and aminopeptidase A (APA were expressed in tumor cells whilst Angiotensin-converting enzyme (ACE was expressed in the endothelial cells of intratumor blood vessels. The expression of ACE, ACE2 and NEP/CD10 was highest in clear cell renal cell carcinoma (CCRCC and papillary renal cell carcinoma (PRCC. The expression of these enzymes correlated with CCRCC aggressiveness. In addition, NEP/CD10 correlated with 15-year overall survival. On the other hand, APA expression was decreased in CCRCC with higher grade and stage. The loss of expression of APA independently correlated with a worse 15-year overall survival. Serum activity of ACE2, NEP/CD10 and APA was significantly higher in renal tumor patients than in healthy subjects. Serum ACE activity was lower in high grade and metastatic CCRCC patients, and NEP/CD10 activity was negatively correlated with UISS (UCLA Integrated Staging System and SSIGN (Mayo Clinic stage, size, grade and necrosis model scores and with overall survival of CCRCC patients. These results suggest a metabolic imbalance of iRAS in renal tumors. This finding should be taken into account in the search of new diagnostic, prognostic and therapeutic tools for this disease.

  14. Blood Pressure Lowering and Safety Improvements With Liver Angiotensinogen Inhibition in Models of Hypertension and Kidney Injury.

    Science.gov (United States)

    Mullick, Adam E; Yeh, Steve T; Graham, Mark J; Engelhardt, Jeffery A; Prakash, Thazha P; Crooke, Rosanne M

    2017-09-01

    Uncontrolled hypertension is an important contributor to cardiovascular disease. Despite the armamentarium of antihypertensive treatments, there remains a need for novel agents effective in individuals who cannot reach acceptable blood pressure levels. Inhibitors targeting the renin-angiotensin-aldosterone system (RAAS) are widely used but may not optimally inhibit RAAS and demonstrate an acceptable safety profile. Experiments were conducted to characterize a series of AGT (angiotensinogen) antisense oligonucleotides (ASOs) and compare their efficacy and tolerability to traditional RAAS blockade. AGT ASOs which target multiple systemic sites of AGT versus an N-acetylgalactosamine-conjugated AGT ASO that targets the liver were compared with captopril and losartan. Spontaneously hypertensive rats fed an 8% NaCl diet, a model of malignant hypertension resistant to standard RAAS inhibitors, demonstrated robust and durable blood pressure reductions with AGT ASO treatments, which was not observed with standard RAAS blockade. Studies in rat models of acute kidney injury produced by salt deprivation revealed kidney injury with ASO treatment that reduced kidney-expressed AGT, but not in animals treated with the N-acetylgalactosamine AGT ASO despite comparable plasma AGT reductions. Administration of either captopril or losartan also produced acute kidney injury during salt deprivation. Thus, intrarenal RAAS derived from kidney AGT, and inhibited by the standard of care, contributes to the maintenance of renal function during severe RAAS challenge. Such improvements in efficacy and tolerability by a liver-selective AGT inhibitor could be desirable in individuals not at their blood pressure goal with existing RAAS blockade. © 2017 American Heart Association, Inc.

  15. Effect of tempol and tempol plus catalase on intra-renal haemodynamics in spontaneously hypertensive stroke-prone (SHSP) and Wistar rats.

    Science.gov (United States)

    Ahmeda, Ahmad F; Rae, Mark G; Al Otaibi, Mohammed F; Anweigi, Lamyia M; Johns, Edward J

    2017-05-01

    Vasoconstriction within the renal medulla contributes to the development of hypertension. This study investigated the role of reactive oxygen species (ROS) in regulating renal medullary and cortical blood perfusion (MBP and CBP respectively) in both stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar rats. CBP and MBP were measured using a laser-Doppler flow meter before and after intra-renal infusion of tempol, the superoxide dismutase (SOD) mimetic or tempol plus catalase, the hydrogen peroxide-degrading enzyme. Tempol infusion significantly elevated blood perfusion within the renal medulla (MBP) in both SHRSP (by 43 ± 7%, P catalase and tempol were co-infused, MBP was again significantly increased in SHRSP (by 57 ± 6%, P < 0.001) and Wistar rats (by 33 ± 6%, P < 0.001), with a significantly greater increase in perfusion being induced in the SHRSP relative to the Wistar rats (P < 0.01). Notably, this increase was significantly greater than in those animals infused with tempol alone (P < 0.01). These results suggest that ROS plays a proportionally greater role in reducing renal vascular compliance, particularly within the renal medulla, in normotensive and hypertensive animals, with effects being greater in the hypertensive animals. This supports the hypothesis that SHRSP renal vasculature might be subjected to elevated level of oxidative stress relative to normotensive animals.

  16. Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats.

    Science.gov (United States)

    Hao, Hui-Feng; Liu, Li-Mei; Pan, Chun-Shui; Wang, Chuan-She; Gao, Yuan-Sheng; Fan, Jing-Yu; Han, Jing-Yan

    2017-01-01

    Objectives: To examine the protective effect of Rhynchophylline (Rhy) on vascular endothelial function in spontaneous hypertensive rats (SHRs) and the underlying mechanism. Methods: Intrarenal arteries of SHRs and Wistar rats were suspended in myograph for force measurement. Expression and phosphorylation of endothelial nitric oxide (NO) synthase (eNOS), Akt, and Src kinase (Src) were examined by Western blotting. NO production was assayed by ELISA. Results: Rhy time- and concentration-dependently improved endothelium-dependent relaxation in the renal arteries from SHRs, but had no effect on endothelium-independent relaxation in SHR renal arteries. Wortmannin (an inhibitor of phosphatidylinositol 3-kinase) or PP2 (an inhibitor of Src) inhibited the improvement of relaxation in response to acetylcholine by 12 h-incubation with 300 μM Rhy. Western blot analysis revealed that Rhy elevated phosphorylations of eNOS, Akt, and Src in SHR renal arteries. Moreover, wortmannin reversed the increased phosphorylations of Akt and eNOS induced by Rhy, but did not affect the phosphorylation of Src. Furthermore, the enhanced phosphorylations of eNOS, Akt, and Src were blunted by PP2. Importantly, Rhy increased NO production and this effect was blocked by inhibition of Src or PI3K/Akt. Conclusion: The present study provides evidences for the first time that Rhy ameliorates endothelial dysfunction in SHRs through the activation of Src-PI3K/Akt-eNOS signaling pathway.

  17. Systematic review and meta-analysis to compare success rates of retrograde intrarenal surgery versus percutaneous nephrolithotomy for renal stones >2 cm: An update.

    Science.gov (United States)

    Kang, Sung Ku; Cho, Kang Su; Kang, Dong Hyuk; Jung, Hae Do; Kwon, Jong Kyou; Lee, Joo Yong

    2017-12-01

    We performed a systematic review and meta-analysis comparing stone-free rates between retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL), using updated, more reliable evidence. Randomized controlled trials comparing RIRS and PCNL for >2 cm stones were identified from electronic databases. Stone-free rates for the procedures were compared by qualitative and quantitative syntheses (meta-analyses). Outcome variables are shown as risk ratios (RRs) with 95% confidence intervals (CIs). Eleven articles were included in this study. Most recently published studies exhibited relatively low quality during quality assessment. For the meta-analysis comparing success (stone-free) rates between PCNL and RIRS, the forest plot using the random-effects model showed an RR of 1.11 (95% CI 1.02-1.21, P stone-free rate of PCNL was superior to that of RIRS using a fixed-effect model (RR 1.07, 95% CI 1.01-1.14, P stones. However, in this meta-analysis, the postoperative stone-free rate of PCNL was higher than that of RIRS in patients with >2 cm renal stones.

  18. Percutaneous nephrolithotomy versus retrograde intrarenal surgery for the treatment of kidney stones up to 2 cm in patients with solitary kidney: a single centre experience.

    Science.gov (United States)

    Bai, Yunjin; Wang, Xiaoming; Yang, Yubo; Han, Ping; Wang, Jia

    2017-01-18

    To compare the treatment outcomes between percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) for the management of stones larger than 2 cm in patients with solitary kidney. One hundred sixteen patients with a solitary kidney who underwent RIRS (n = 56) or PCNL (n = 60) for large renal stones (>2 cm) between Jan 2010 and Nov 2015 have been considered. The patients' characteristics, stone characteristics, operative time, incidence of complications, hospital stay, and stone-free rates (SFR) have been evaluated. SFRs after one session were 19.6% and 35.7% for RIRS and PCNL respectively (p = 0.047), but the SFR at 3 months follow-up comparable in both groups (82.1% vs. 88.3%, p = 0.346). The calculated mean operative time for RIRS was longer (p stone clearance can be achieved with multi-session RIRS in the treatment of renal stones larger than 2 cm in patients with solitary kidney. RIRS can be considered as an alternative to PCNL in selected cases.

  19. The comparison of minimally invasive percutaneous nephrolithotomy and retrograde intrarenal surgery for stones larger than 2 cm in patients with a solitary kidney: a matched-pair analysis.

    Science.gov (United States)

    Zeng, Guohua; Zhu, Wei; Li, Jiasheng; Zhao, Zhijian; Zeng, Tao; Liu, Chenli; Liu, Yang; Yuan, Jian; Wan, Shaw P

    2015-08-01

    To compare the treatment outcomes between retrograde intrarenal surgery (RIRS) and minimally invasive percutaneous nephrolithotomy (MPCNL) for the management of stones larger than 2 cm in patients with solitary kidney. Between December 2012 and March 2014, 53 patients with a solitary kidney suffering from urinary stones larger than 2 cm were treated with RIRS. The outcomes of these patients were compared to a cohort of similar solitary kidney stone patients who underwent MPCNL using a matched-pair analysis (1:1 scenario). Cases were matched sequentially using the following criteria: size, number and location of stones, age, BMI, gender and previous ipsilateral open surgery. A stone-free rate (SFR) of 43.4 % was achieved after a single procedure in patients treated with RIRS and a SFR of 71.70 % in patients treated with MPCNL (p = 0.003). The operative time for RIRS was longer (p = 0.002), but the median hospital stay was shorter (p kidney suffering from stones larger than 2 cm in size who undergo MPCNL had a higher SFR than RIRS. The complications were comparable in both groups. Even though RIRS patients spent less time in hospital, this procedure might not be an effective treatment as MPCNL in solitary kidneys with larger and multiple stones.

  20. A true champion of Hungarian kidney research and nephrology education--tribute to László Rosivall.

    Science.gov (United States)

    Peti-Peterdi, János; Navar, L G; Darwin Bell, P; Casellas, D; Carmines, P K; Inscho, E W; Oparil, S

    2009-09-01

    This article pays tribute to the tremendous achievements of Dr. László Rosivall in renal (patho)physiology research and nephrology education in Hungary on the occasion of his 60th birthday. For the past several decades Dr. Rosivall has been a charismatic leader of academic institutions, national and international societies, foundations in physiology, nephrology and hypertension, but the most important of his many contributions, is his role as a scientist. He earned his MD with Summa cum Laude at Semmelweis University (1973) and was invited immediately after that to join the laboratory of Hársing. He studied the distribution of intra-renal blood flow employing then state-of-the-art methods as well as developed his own technique at Semmelweis University and at the University of Bergen with Knut Aukland. This led to his PhD thesis and degree in 1980. An important determinant of his early basic scientific training and development was his postdoctoral research fellowship and later many visiting professorships in the Nephrology Research and Training Center (NRTC) at the University of Alabama at Birmingham, Birmingham, AL, USA between 1981 and 1983. Actually, this research fellowship not only impacted his own future career, but it also cleared the path for many other young Hungarian scientists who later trained with Dr. Rosivall and then at UAB. The early 1980s were the years of significant scientific discoveries and the NRTC team at UAB made important contributions by their studies on renal and glomerular hemodynamics, the renin-angiotensin system (12, 19, 22) and by the development of classic experimental techniques like renal micropuncture, microperfusion, and the juxtamedullary nephron preparation (3) that are still being used worldwide. When Dr. Rosivall joined UAB in the 1980s, the team at the NRTC included Drs. Navar, Bell, Inscho, Carmines, Casellas, and Oparil, among many others, who share their fond memories of working with Dr. Rosivall in this article.