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Sample records for renin-angiotensin-aldosterone system inhibitors

  1. 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 This article has been retracted at the request of the Editors and the Publisher.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 Online-first articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus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

  2. New drugs for the treatment of hyperkalemia in patients treated with renin-angiotensin-aldosterone system inhibitors -- hype or hope?

    Science.gov (United States)

    Tamargo, Juan; Caballero, Ricardo; Delpón, Eva

    2014-11-01

    Hyperkalemia (serum potassium >5.5 mmol/L) may result from increased potassium intake, impaired distribution between the intracellular and extracellular spaces, and/or reduced renal excretion. Renin-angiotensin-aldosterone system inhibitors (RAASIs) represent an important therapeutic strategy in patients with hypertension, heart failure, chronic kidney disease, and diabetes, but hyperkalemia is a key limitation to fully titrate RAASIs in these patients who are most likely to benefit from treatment. Thus, we need new drugs to control hyperkalemia in these patients while maintaining the use of RAASIs. We review two new polymer-based, non-systemic agents under clinical development, patiromer calcium and zirconium silicate, designed to increase potassium loss via the gastrointestinal tract for the management of hyperkalemia.

  3. Preeclampsia, the Renin-Angiotensin-Aldosterone System and beyond

    NARCIS (Netherlands)

    K. Verdonk (Koen)

    2015-01-01

    markdownabstract__Abstract__ The renin-angiotensin-aldosterone system (RAAS) plays an essential role in the regulation of blood pressure and body fluid homeostasis, but also contributes importantly to the pathophysiology of hypertension, renal disease and heart failure. Clinically, the RAAS is of g

  4. Cardiovascular Risk Reduction with Renin-Angiotensin Aldosterone System Blockade

    Directory of Open Access Journals (Sweden)

    Nancy Houston Miller

    2010-01-01

    Full Text Available This paper examines the evidence supporting treatments within the renin-angiotensin aldosterone system (RAS, the role cardioprotection plays within the management of hypertension, considerations around medication adherence, and the role of the nurse or nurse practitioner in guiding patients to achieve higher hypertension control rates. A large body of data now exists to support the use of angiotensin receptor blockers (ARBs and angiotensin-converting enzyme inhibitors (ACEIs which act on RAS, in the management of hypertension and their effect on cardiovascular risk reduction. Current evidence suggests that inhibition of the RAS is an important target for cardioprotection. RAS inhibition controls blood pressure and also reduces target-organ damage. This is especially important in populations at high-risk for damage including patients with diabetes and those with chronic kidney disease. Both ARBs and ACEIs target the RAS offering important reductions in both BP and target organ damage.

  5. Combination therapy with renin-angiotensin-aldosterone system inhibitor telmisartan and serine protease inhibitor camostat mesilate provides further renoprotection in a rat chronic kidney disease model.

    Science.gov (United States)

    Narita, Yuki; Ueda, Miki; Uchimura, Kohei; Kakizoe, Yutaka; Miyasato, Yoshikazu; Mizumoto, Teruhiko; Morinaga, Jun; Hayata, Manabu; Nakagawa, Terumasa; Adachi, Masataka; Miyoshi, Taku; Sakai, Yoshiki; Kadowaki, Daisuke; Hirata, Sumio; Mukoyama, Masashi; Kitamura, Kenichiro

    2016-02-01

    We previously reported that camostat mesilate (CM) had renoprotective and antihypertensive effects in rat CKD models. In this study, we examined if CM has a distinct renoprotective effect from telmisartan (TE), a renin-angiotensin-aldosterone system (RAS) inhibitor, on the progression of CKD. We evaluated the effect of CM (400 mg/kg/day) and/or TE (10 mg/kg/day) on renal function, oxidative stress, renal fibrosis, and RAS components in the adenine-induced rat CKD model following 5-weeks treatment period. The combination therapy with CM and TE significantly decreased the adenine-induced increase in serum creatinine levels compared with each monotherapy, although all treatment groups showed similar reduction in blood pressure. Similarly, adenine-induced elevation in oxidative stress markers and renal fibrosis markers were significantly reduced by the combination therapy relative to each monotherapy. Furthermore, the effect of the combination therapy on plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was similar to that of TE monotherapy, and CM had no effect on both PRA and PAC, suggesting that CM has a distinct pharmacological property from RAS inhibition. Our findings indicate that CM could be a candidate drug for an add-on therapy for CKD patients who had been treated with RAS inhibitors.

  6. Addressing the theoretical and clinical advantages of combination therapy with inhibitors of the renin-angiotensin-aldosterone system: antihypertensive effects and benefits beyond BP control.

    Science.gov (United States)

    Ferrario, Carlos M

    2010-02-27

    This article reviews the importance of the renin-angiotensin-aldosterone system (RAAS) in the cardiometabolic continuum; presents the pros and cons of dual RAAS blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs); and examines the theoretical and practical benefits supporting the use of direct renin inhibitors (DRIs) in combination with ACEIs or ARBs. The author reviewed the literature for key publications related to the biochemical physiology of the RAAS and the pharmacodynamic effects of ACEIs, ARBs, and DRIs, with a particular focus on dual RAAS blockade with these drug classes. Although ACEI/ARB combination therapy produces modest improvement in BP, it has not resulted in the major improvements predicted given the importance of the RAAS across the cardiorenal disease continuum. This may reflect the fact that RAAS blockade with ACEIs and/or ARBs leads to exacerbated renin release through loss of negative-feedback inhibition, as well as ACE/aldosterone escape through RAAS and non-RAAS-mediated mechanisms. Plasma renin activity (PRA) is an independent predictor of morbidity and mortality, even for patients receiving ACEIs and ARBs. When used alone or in combination with ACEIs and ARBs, the DRI aliskiren effectively reduces PRA. Reductions in BP are greater with these combinations, relative to the individual components alone. It is possible that aliskiren plus either an ACEI or ARB may provide greater RAAS blockade than monotherapy with ACEIs or ARBs, and lead to additive improvement in BP and clinically important outcomes. Copyright 2009 Elsevier Inc. All rights reserved.

  7. Mechanism of renin-angiotensin-aldosterone system inhibitors%肾素-血管紧张素-醛固酮系统抑制剂的作用机制

    Institute of Scientific and Technical Information of China (English)

    朱凌倜; 周京敏

    2013-01-01

    Renin-angiotensin-aldosterone system (RAAS) is a complex network system in regulating cardiovascular and renal function. RAAS activation plays an extremely important role in the development and prognosis of hypertension, myocardial remodeling after acute myocardial infarction, acute and chronic heart failure and renal insufifciency. The symptoms and prognosis of patients with above-mentioned diseases can be signiifcantly improved by blocking different levels of RAAS. This article reviews the mechanism of several RAAS inhibitors which are commonly used in clinic.%肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system, RAAS)是一种调控心血管和肾功能的复杂的网络系统。RAAS的激活在高血压、急性心肌梗死后的心肌重塑、急性和慢性心力衰竭以及肾功能不全等多种疾病的进展中起着重要的作用,而RAAS抑制剂能够显著延缓上述疾病的进展和改善患者的预后。本文就目前临床常用的几类RAAS抑制剂的作用机制作一概述。

  8. Role of the Renin-Angiotensin-Aldosterone System and Its Pharmacological Inhibitors in Cardiovascular Diseases: Complex and Critical Issues.

    Science.gov (United States)

    Borghi, Claudio; Rossi, Francesco

    2015-12-01

    Hypertension is one of the major risk factor able to promote development and progression of several cardiovascular diseases, including left ventricular hypertrophy and dysfunction, myocardial infarction, stroke, and congestive heart failure. Also, it is one of the major driven of high cardiovascular risk profile in patients with metabolic complications, including obesity, metabolic syndrome and diabetes, as well as in those with renal disease. Thus, effective control of hypertension is a key factor for any preventing strategy aimed at reducing the burden of hypertension-related cardiovascular diseases in the clinical practice. Among various regulatory and contra-regulatory systems involved in the pathogenesis of cardiovascular and renal diseases, renin-angiotensin system (RAS) plays a major role. However, despite the identification of renin and the availability of various assays for measuring its plasma activity, the specific pathophysiological role of RAS has not yet fully characterized. In the last years, however, several notions on the RAS have been improved by the results of large, randomized clinical trials, performed in different clinical settings and in different populations treated with RAS inhibiting drugs, including angiotensin converting enzyme (ACE) inhibitors and antagonists of the AT1 receptor for angiotensin II (ARBs). These findings suggest that the RAS should be considered to have a central role in the pathogenesis of different cardiovascular diseases, for both therapeutic and preventive purposes, without having to measure its level of activation in each patient. The present document will discuss the most critical issues of the pathogenesis of different cardiovascular diseases with a specific focus on RAS blocking agents, including ACE inhibitors and ARBs, in the light of the most recent evidence supporting the use of these drugs in the clinical management of hypertension and hypertension-related cardiovascular diseases.

  9. Renal damage after myocardial infarction is prevented by renin-angiotensin-aldosterone-system intervention

    NARCIS (Netherlands)

    Windt, Willemijn A. K. M.; Eijkelkamp, Wouter B. A.; Henning, Robert H.; Kluppel, Alex C. A.; de Graeff, Pieter A.; Hillege, Hans L.; Schaefer, Stefan; de Zeeuw, Dick; van Dokkum, Richard P. E.

    2006-01-01

    Recently, it was shown that myocardial infarction aggravates preexistent mild renal damage that is elicited by unilateral nephrectomy in rats. The mechanism behind this cardiorenal interaction likely involves the renin-angiotensin-aldosterone-system and/or vasoactive peptides that are metabolized by

  10. Fibroblast Growth Factor 23 and the Antiproteinuric Response to Dietary Sodium Restriction During Renin-Angiotensin-Aldosterone System Blockade

    NARCIS (Netherlands)

    Humalda, Jelmer K; Lambers Heerspink, Hiddo J; Kwakernaak, Arjan J; Slagman, Maartje C J; Waanders, Femke; Vervloet, Marc G; Ter Wee, Pieter M; Navis, Gerarda; de Borst, Martin H

    2015-01-01

    Background: Residual proteinuria during renin-angiotensin-aldosterone system (RAAS) blockade is a major renal and cardiovascular risk factor in chronic kidney disease. Dietary sodium restriction potentiates the antiproteinuric effect of RAAS blockade, but residual proteinuria remains in many patient

  11. Fibroblast growth factor 23 and the antiproteinuric response to dietary sodium restriction during renin-angiotensin-aldosterone system blockade.

    NARCIS (Netherlands)

    Humalda, J.K.; Lambers Heerspink, H.J.; Kwakernaak, A.J.; Slagman, M.C.; Waanders, F.; Vervloet, M.G.; Wee, P.M. Ter; Navis, G.; Borst, M.H. de; Wee, P.M. ter; Vervloet, M.; Bindels, R.J.; Hoenderop, J.G.J.; Hillebrands, J.L.

    2015-01-01

    BACKGROUND: Residual proteinuria during renin-angiotensin-aldosterone system (RAAS) blockade is a major renal and cardiovascular risk factor in chronic kidney disease. Dietary sodium restriction potentiates the antiproteinuric effect of RAAS blockade, but residual proteinuria remains in many patient

  12. Fibroblast Growth Factor 23 and the Antiproteinuric Response to Dietary Sodium Restriction During Renin-Angiotensin-Aldosterone System Blockade

    NARCIS (Netherlands)

    Humalda, Jelmer K; Lambers Heerspink, Hiddo J; Kwakernaak, Arjan J; Slagman, Maartje C J; Waanders, Femke; Vervloet, Marc G; Ter Wee, Pieter M; Navis, Gerarda; de Borst, Martin H

    2015-01-01

    Background: Residual proteinuria during renin-angiotensin-aldosterone system (RAAS) blockade is a major renal and cardiovascular risk factor in chronic kidney disease. Dietary sodium restriction potentiates the antiproteinuric effect of RAAS blockade, but residual proteinuria remains in many patient

  13. Fibroblast growth factor 23 and the antiproteinuric response to dietary sodium restriction during renin-angiotensin-aldosterone system blockade.

    NARCIS (Netherlands)

    Humalda, J.K.; Lambers Heerspink, H.J.; Kwakernaak, A.J.; Slagman, M.C.; Waanders, F.; Vervloet, M.G.; Wee, P.M. Ter; Navis, G.; Borst, M.H. de; Wee, P.M. ter; Vervloet, M.; Bindels, R.J.; Hoenderop, J.G.J.; Hillebrands, J.L.

    2015-01-01

    BACKGROUND: Residual proteinuria during renin-angiotensin-aldosterone system (RAAS) blockade is a major renal and cardiovascular risk factor in chronic kidney disease. Dietary sodium restriction potentiates the antiproteinuric effect of RAAS blockade, but residual proteinuria remains in many patient

  14. Fibroblast Growth Factor 23 and the Antiproteinuric Response to Dietary Sodium Restriction During Renin-Angiotensin-Aldosterone System Blockade

    NARCIS (Netherlands)

    Humalda, Jelmer K; Lambers Heerspink, Hiddo J; Kwakernaak, Arjan J; Slagman, Maartje C J; Waanders, Femke; Vervloet, Marc G; Ter Wee, Pieter M; Navis, Gerarda; de Borst, Martin H

    Background: Residual proteinuria during renin-angiotensin-aldosterone system (RAAS) blockade is a major renal and cardiovascular risk factor in chronic kidney disease. Dietary sodium restriction potentiates the antiproteinuric effect of RAAS blockade, but residual proteinuria remains in many

  15. Fibroblast growth factor 23 and the antiproteinuric response to dietary sodium restriction during renin-angiotensin-aldosterone system blockade.

    NARCIS (Netherlands)

    Humalda, J.K.; Lambers Heerspink, H.J.; Kwakernaak, A.J.; Slagman, M.C.; Waanders, F.; Vervloet, M.G.; Wee, P.M. Ter; Navis, G.; Borst, M.H. de; Wee, P.M. ter; Vervloet, M.; Bindels, R.J.; Hoenderop, J.G.J.; Hillebrands, J.L.

    2015-01-01

    BACKGROUND: Residual proteinuria during renin-angiotensin-aldosterone system (RAAS) blockade is a major renal and cardiovascular risk factor in chronic kidney disease. Dietary sodium restriction potentiates the antiproteinuric effect of RAAS blockade, but residual proteinuria remains in many

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

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    Slavnov, V.N.; Yakovlev, A.A.; Gandzha, T.I.; Yugrinov, O.G. (AN Ukrainskoj SSR, Kiev)

    1985-01-01

    In 110 patients suffering from various forms of arterial hypertension (hypertension, aldosteronoma, phaeochromocytoma, corticosteroma) the parameters of the system renin-angiotensin-aldosterone were measured. Basal values of aldosterone, renin activity in blood as well as their concentration in blood taken from the vena cava inferior, renal and adrenal veins during selective renography were determined. 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 (furosemide) stress was evaluated. It was found, that the system renin-angiotensin-aldosterone 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-hours rhythm of their concentrations in serum and the reaction to acute Lasix stress. The radioimmunoassays of quantitative parameters of the renin-angiotensin-aldosterone system are decisive for the differential diagnosis of hypertension and adrenal gland tumors connected with a hypertension syndrome. They facilitate a rational choice of the hypertension therapy and the daily distribution of the medications for patients with hypertension. The radioimmunoassays can be used for checking the efficiency of medications and surgery.

  17. 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.

  18. Renin-angiotensin-aldosterone system in the elderly: rational use of aliskiren in managing hypertension

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    Karl Andersen

    2009-03-01

    Full Text Available Karl AndersenDepartment of Medicine, Division of Cardiology, Landspitali University Hospital, University of Iceland, Reykjavik, IcelandAbstract: The overall purpose of hypertension treatment is 2-fold. First, patients often have symptoms that are related to their high blood pressure and although subtle in many instances may be improved dramatically by blood pressure control. The main reason for blood pressure treatment, however, is to reduce the burden of cardiovascular complications and end organ damage related to the condition. This may be considered the ultimate goal of blood pressure treatment. In this respect, actual blood pressure measurements may be seen as surrogate end points as the organ protective effects of two antihypertensive agents may differ significantly even though their blood pressure lowering effects are similar. Thus beta-blockers, once seen as first-line treatment of hypertension for most patients, now are considered as third- or fourth-line agents according to the latest NICE guidelines (National Institute for Health and Clinical Excellence, www.nice.org.uk/CG034. On the other hand, agents that inhibit the activity of the renin-angiotensin-aldosterone system (RAAS are being established as safe, effective and end organ protective in numerous clinical trials, resulting in their general acceptance as first-line treatment in most patients with stage 2 hypertension. This shift in emphasis from beta-blockers and thiazide diuretics is supported by numerous clinical trials and has proven safe and well tolerated by patients. The impact of this paradigm shift will have to be established in future long-term randomized clinical trials. The optimal combination treatment with respect to end organ protection has yet to be determined. Most combinations will include either a RAAS active agent and calcium channel blocker or two separate RAAS active agents working at different levels of the cascade. In this respect direct renin inhibitors

  19. Renin-angiotensin-aldosterone system blockade in chronic kidney disease: current strategies and a look ahead.

    Science.gov (United States)

    Viazzi, Francesca; Bonino, Barbara; Cappadona, Francesca; Pontremoli, Roberto

    2016-08-01

    The Renin-Angiotensin-Aldosterone System (RAAS) is profoundly involved in the pathogenesis of renal and cardiovascular organ damage, and has been the preferred therapeutic target for renal protection for over 30 years. Monotherapy with either an Angiotensin Converting Enzime Inhibitor (ACE-I) or an Angiotensin Receptor Blocker (ARB), together with optimal blood pressure control, remains the mainstay treatment for retarding the progression toward end-stage renal disease. Combining ACE-Is and ARBs, or either one with an Aldosterone Receptor Antagonist (ARA), has been shown to provide greater albuminuria reduction, and to possibly improve renal outcome, but at an increased risk of potentially severe side effects. Moreover, combination therapy has failed to provide additional cardiovascular protection, and large prospective trials on hard renal endpoints are lacking. Therefore this treatment should, at present, be limited to selected patients with residual proteinuria and high renal risk. Future studies with novel agents, which directly act on the RAAS at multiple levels or have a more favourable side effect profile, are greatly needed to further explore and define the potential for and the limitations of profound pharmacologic RAAS inhibition.

  20. New drug therapies interfering with the renin-angiotensin-aldosterone system for resistant hypertension.

    Science.gov (United States)

    Monge, Matthieu; Lorthioir, Aurélien; Bobrie, Guillaume; Azizi, Michel

    2013-12-01

    There is a persistent need for the development of new antihypertensive drugs, because the control of blood pressure is still not achievable in a significant proportion of hypertensive patients. Since the approval in 2007 of aliskiren, no other new antihypertensive based on new mechanism(s) of action have been approved. In fact, the development of promising novel drugs has been stopped for safety, efficacy or marketing reasons. Despite these difficulties, the pipeline is not dry and different new antihypertensive strategies targeting the renin-angiotensin-aldosterone pathway, are in clinical development stage. The dual angiotensin II receptor-neprilysin inhibitor LCZ696, a single molecule synthetized by cocrystallisation of valsartan and the neprilysin inhibitor prodrug AHU377 is in development for resistant hypertension and for heart failure. Daglutril is a dual neprylisin-endothelin converting enzyme inhibitor which was shown to decrease BP in patients with type 2 diabetic nephropathy. Aldosterone synthase inhibitors and the third and fourth generation non-steroidal dihydropyridine based mineralocorticoid receptors blockers are new ways to target the multiple noxious effects of aldosterone in the kidney, vessels and heart. Centrally acting aminopeptidase A inhibitors block brain angiotensin III formation, one of the main effector peptides of the brain renin angiotensin system. However, a long time will be still necessary to evaluate extensively the efficacy and safety of these new approaches. In the mean time, using appropriate and personalized daily doses of available drugs, decreasing physician inertia, improving treatment adherence, improving access to healthcare and reducing treatment costs remain major objectives to reduce the incidence of resistant hypertension.

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

    Institute of Scientific and Technical Information of China (English)

    Yan-Huan Feng; Ping Fu

    2016-01-01

    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 ofmonotherapy, 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 evidence-based practice.

  2. 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

  3. Biomarkers of activation of renin-angiotensin-aldosterone system in heart failure: how useful, how feasible?

    Science.gov (United States)

    Emdin, Michele; Fatini, Cinzia; Mirizzi, Gianluca; Poletti, Roberta; Borrelli, Chiara; Prontera, Concetta; Latini, Roberto; Passino, Claudio; Clerico, Aldo; Vergaro, Giuseppe

    2015-03-30

    Renin-angiotensin-aldosterone system (RAAS), participated by kidney, liver, vascular endothelium, and adrenal cortex, and counter-regulated by cardiac endocrine function, is a complex endocrine system regulating systemic functions, such as body salt and water homeostasis and vasomotion, in order to allow the accomplishment of physiological tasks, such as orthostasis, physical and emotional stimuli, and to react towards the hemorrhagic insult, in tight conjunction with other neurohormonal axes, namely the sympathetic nervous system, the endothelin and vasopressin systems. The systemic as well as the tissue RAAS are also dedicated to promote tissue remodeling, particularly relevant after damage, when chronic activation may configure as a maladaptive response, leading to fibrosis, hypertrophy and apoptosis, and organ dysfunction. RAAS activation is a fingerprint of systemic arterial hypertension, kidney dysfunction, vascular atherosclerotic disease, and is definitely an hallmark of heart failure, which rapidly shifts from organ disease to a disorder of neurohormonal regulatory systems. Chronic RAAS activation is an indirect or direct target of most effective pharmacological treatments in heart failure, such as beta-blockers, inhibitors of angiotensin converting enzyme, angiotensin receptor blockers, direct renin inhibitors, and mineralocorticoid receptor blockers. Biomarkers of RAAS activation are available, with different feasibility and accuracy, such as plasma renin activity, renin, angiotensin II, and aldosterone, which all accompany the increasing clinical severity of heart failure disease, and are well recognized prognostic factors, even in patients with optimal therapy. Polymorphisms influencing the expression and activity of RAAS pathways have been recognized as clinically relevant biomarkers, likely influencing either the individual clinical phenotype, or the response to drugs. This solid, growing evidence strongly suggests the rationale for the use of

  4. Chronobiology and Pharmacologic Modulation of the Renin-Angiotensin-Aldosterone System in Dogs: What Have We Learned?

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    Mochel, Jonathan P; Danhof, Meindert

    2015-01-01

    Congestive heart failure (CHF) is a primary cause of morbidity and mortality with an increasing prevalence in human and canine populations. Recognition of the role of renin-angiotensin-aldosterone system (RAAS) overactivation in the pathophysiology of CHF has led to significant medical advances. By decreasing systemic vascular resistance and angiotensin II (AII) production, angiotensin-converting enzyme (ACE) inhibitors such as benazepril improve cardiac hemodynamics and reduce mortality in human and dog CHF patients. Although several experiments have pointed out that efficacy of ACE inhibitors depends on the time of administration, little attention is paid to the optimum time of dosing of these medications. A thorough characterization of the chronobiology of the renin cascade has the potential to streamline the therapeutic management of RAAS-related diseases and to help determining the optimal time of drug administration that maximizes efficacy of ACE inhibitors, while minimizing the occurrence of adverse effects. We have developed an integrated pharmacokinetic-pharmacodynamic model that adequately captures the disposition kinetics of the paradigm drug benazeprilat, as well as the time-varying changes of systemic renin-angiotensin-aldosterone biomarkers, without and with ACE inhibition therapy. Based on these chronobiological investigations, the optimal efficacy of ACE inhibitors is expected with bedtime dosing. The data further show that benazepril influences the dynamics of the renin-angiotensin-aldosterone cascade, resulting in a profound decrease in AII and aldosterone (ALD), while increasing renin activity for about 24 h. From the results of recent investigations in human, it is hypothesized that reduction of AII and ALD is one of the drivers of increased survival and improved quality of life in dogs receiving ACE inhibitors. To support and consolidate this hypothesis, additional efforts should be directed toward the collection of circulating RAAS peptides

  5. Combined use of renin-angiotensin-aldosterone system-acting agents: a cross-sectional study.

    Science.gov (United States)

    Farcas, Andreea; Leucuta, Daniel; Bucsa, Camelia; Mogosan, Cristina; Dumitrascu, Dan

    2016-12-01

    Background Due to recent EU warnings and restrictions on the combined use of renin-angiotensin-aldosterone system (RAAS)-acting agents, and the seriousness of the associated harm, we analyzed the prescription of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) as dual therapy or associated with spironolactone. Setting An administrative claims database of a regional hospital in Romania. Methods We retrospectively included all adult patients hospitalized during 18 months in 2013-2014, discharged with a prescription of a RAAS-acting agent. Main outcome measures Counts of ACEIs and ARBs co-prescription, of ACEIs or ARBs combined with spironolactone, co-morbidities, co-medication, creatinine, and electrolytes assessment and values. Results Out of 1697 patients with a prescription of a RAAS-acting agent, 24 (1.4 %) were co-prescribed ACEIs and ARBs, and 416 (24.5 %) ACEIs or ARBs with spironolactone. Patients prescribed dual ACEI/ARB therapy and the ones with ACEI or ARB-spironolactone combination had significantly higher prevalence of increased creatinine level before discharge, compared to the ACEI and ARB monotherapy groups (48 and 31 % compared to 17 and 27 %). Subjects with diabetes, heart failure, ischaemic heart disease, or urea ≥40 mg/dL had higher odds of having ACEI or ARB-spironolactone combination compared to monotherapy, while hypertension and renal disease subjects had lower odds. Similar findings were comparing dual ACEI/ARB therapy to monotherapy except heart failure (not statistically significant). Conclusion Overall, the prevalence of use of dual therapy was low. The combined use of RAAS-acting agents was higher in patients with known risk factors for further renal function deterioration, compared to the ones without.

  6. 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 Henrik

    2006-01-01

    OBJECTIVE: Several studies have shown activation of the renin-angiotensin-aldosterone system (RAAS) in cirrhosis. Although the activated RAAS may have several determinants, the system is often considered a surrogate marker of effective hypovolaemia. In this study we investigated the activity...

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

    NARCIS (Netherlands)

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

    2008-01-01

    textabstractAims: 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

  8. Effect of renin-angiotensin-aldosterone system gene polymorphisms on blood pressure response to antihypertensive treatment

    Institute of Scientific and Technical Information of China (English)

    JIANG Xiao; SHENG Hai-hui; LIN Gang; LI Jian; LU Xin-zheng; CHENG Yun-lin; HUANG Jun; XIAO Hua-sheng; ZHAN Yi-yang

    2007-01-01

    Background The renin-angiotensin-aldosterone system (RAAS) is important for the development of essential hypertension, and many antihypertensive drugs target it. This study was undertaken to determine whether polymorphisms in the renin-angiotensin-aldosterone system are related to the blood pressure (BP) response to diuretic treatment in a Chinese Han ethnic population.Methods Fifty-four patients with essential hypertension received hydrochlorothiazide (12.5 mg, once daily) as monotherapy for four weeks. Seven polymorphisms in RAAS genes were genotyped by gene chip technology. The relationship between these polymorphisms and the change in blood pressure was observed after the 4-week treatment.Results The patients with angiotensinogen (AGT) -6G allele showed a greater reduction in diastolic BP (P= 0.025) and mean BP (P=0.039) than those carrying AA genotype. Patients carrying aldosterone synthase (CYP11B2) CC genotype exhibited a greater BP reduction than those carrying CT and TT genotypes (systolic BP: P= 0.030; diastolic BP: P= 0.026; mean BP: P=0.003). In addition, patients with a combination of CYP11B2 CC genotype and angiotensin converting enzyme (ACE) D allele might have a more pronounced reduction of systolic BP than those with any other genotypic combinations of the two genes (P= 0.007).Conclusions AGT-6G allele, CYP11B2 -344CC genotype and its combination with ACE D allele are associated with BP response to hydrochlorothiazide treatment. Larger studies are warranted to validate this finding.

  9. Analysis of renin-angiotensin-aldosterone system gene polymorphisms in resistant hypertension

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    S.R.S. Freitas

    2007-03-01

    Full Text Available Essential hypertension is a disease multifactorially triggered by genetic and environmental factors. The contribution of genetic polymorphisms of the renin-angiotensin-aldosterone system and clinical risk factors to the development of resistant hypertension was evaluated in 90 hypertensive patients and in 115 normotensive controls living in Southwestern Brazil. Genotyping for insertion/deletion of angiotensin-converting enzyme, angiotensinogen M235T, angiotensin II type 1 receptor A1166C, aldosterone synthase C344T, and mineralocorticoid receptor A4582C polymorphisms was performed by PCR, with further restriction analysis when required. The influence of genetic polymorphisms on blood pressure variation was assessed by analysis of the odds ratio, while clinical risk factors were evaluated by logistic regression. Our analysis indicated that individuals who carry alleles 235-T, 1166-A, 344-T, or 4582-C had a significant risk of developing resistant hypertension (P < 0.05. Surprisingly, when we tested individuals who carried the presumed risk genotypes A1166C, C344T, and A4582C we found that these genotypes were not associated with resistant hypertension. However, a gradual increase in the risk to develop resistant hypertension was detected when the 235-MT and TT genotypes were combined with one, two or three of the supposedly more vulnerable genotypes - A1166C (AC/AA, C344T (TC/TT and A4582C (AC/CC. Analysis of clinical parameters indicated that age, body mass index and gender contribute to blood pressure increase (P < 0.05. These results suggest that unfavorable genetic renin-angiotensin-aldosterone system patterns and clinical risk variables may contribute to increasing the risk for the development of resistant hypertension in a sample of the Brazilian population.

  10. Atlas of tissue renin-angiotensin-aldosterone system in human: A transcriptomic meta-analysis.

    Science.gov (United States)

    Nehme, Ali; Cerutti, Catherine; Dhaouadi, Nedra; Gustin, Marie Paule; Courand, Pierre-Yves; Zibara, Kazem; Bricca, Giampiero

    2015-05-20

    Tissue renin-angiotensin-aldosterone system (RAAS) has attracted much attention because of its physiological and pharmacological implications; however, a clear definition of tissue RAAS is still missing. We aimed to establish a preliminary atlas for the organization of RAAS across 23 different normal human tissues. A set of 37 genes encoding classical and novel RAAS participants including gluco- and mineralo-corticoids were defined as extended RAAS (extRAAS) system. Microarray data sets containing more than 10 normal tissues were downloaded from the GEO database. R software was used to extract expression levels and construct dendrograms of extRAAS genes within each data set. Tissue co-expression modules were then extracted from reproducible gene clusters across data sets. An atlas of the maps of tissue-specific organization of extRAAS was constructed from gene expression and coordination data. Our analysis included 143 data sets containing 4933 samples representing 23 different tissues. Expression data provided an insight on the favored pathways in a given tissue. Gene coordination indicated the existence of tissue-specific modules organized or not around conserved core groups of transcripts. The atlas of tissue-specific organization of extRAAS will help better understand tissue-specific effects of RAAS. This will provide a frame for developing more effective and selective pharmaceuticals targeting extRAAS.

  11. Gene polymorphisms of renin-angiotensin-aldosterone system components and the progression of chronic kidney diseases

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    Agata Kujawa-Szewieczek

    2010-08-01

    Full Text Available The renin-angiotensin-aldosterone system (RAAS plays an important role in the pathogenesis of hypertension as well as cardiovascular diseases and chronic kidney diseases. Among the most frequently studied RAAS gene polymorphisms are the angiotensin-converting enzyme insertion/deletion (I/D, angiotensinogen M235T and angiotensin II receptor type 1 A1166C polymorphisms.A significant correlation was found between the I/D polymorphism and cardiovascular morbidity and mortality rates. However, there was no significant correlation between I/D, M235T, A1166C polymorphism and arterial hypertension. The role of I/D polymorphism in the development and progression of chronic kidney disease is also non-conclusive. However, DD genotype has been identified as relevant for loss of renal function both in patients with IgA nephropathy and in patients of Asian origin with diabetic nephropathy.The relationship between RAAS gene polymorphism and transplanted kidney function has not been confirmed in large prospective and retrospective studies. Conclusion: there is no clear opinion concerning the influence of RAAS genotypes on the prevalence of post-transplant hypertension or erythrocytosis.Although a role of RAAS gene polymorphism in kidney function deterioration could not be ruled out, it is more likely that a variety of genetic and environmental factors influence the progression of chronic kidney diseases.

  12. THE GENDER FEATURES OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM IN HYPERTENSIVE PATIENTS

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    V. I. Podzolkov

    2010-01-01

    Full Text Available Aim. To study the correlation of the renin-angiotensin-aldosterone system (RAAS activity with the female sex hormone levels and markers of target organ damage in patients with arterial hypertension (HT.Material and methods. Patients with HT (20 men and 39 postmenopausal women were involved into the study. The dynamic renal angioscintigraphy and echocardiography were performed, plasma rennin activity (PRA, levels of aldosterone, estradiole and 17-hydroxiprogesterone were determined by radioimmunoassay.Results. Higher aldosterone level was found in women in comparison with men (212,5±123,9 pg/ml and 148,9±82,5 pg/m, respectively, р=0,03. Negative relations between aldosterone and estradiol levels (r=-0,3; p=0,04, and between aldosterone and 17-hydroxyprogesterone levels (r=-0,318; p=0,04, and positive relations between aldosterone concentration and PRA (r=0,555; p=0,04 was found in women. Besides, correlation between levels of female sex hormones, aldosterone and renal blood flow indicators, glomerular filtration rate, left ventricular mass index (LVMI were found in women. These correlations were not found in men.Conclusion. The gender differences of RAAS activity were revealed with higher aldosterone level in postmenopausal hypertensive women in comparison with men. Relationships between PRA, levels of aldosterone and female sex hormones and renal blood flow indices, LVMI were also found in women.

  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. High pulse pressure is not associated with abnormal activation of the renin-angiotensin-aldosterone system in repaired aortic coarctation.

    Science.gov (United States)

    Pedersen, T A L; Pedersen, E B; Munk, K; Hjortdal, V E; Emmertsen, K; Andersen, N H

    2015-04-01

    We investigated the relationship between pulse pressure (PP)--a surrogate marker of arterial stiffness-and activity of the renin-angiotensin-aldosterone system (RAAS) in adult patients with repaired coarctation and normal left ventricular (LV) function. A total of 114 patients (44 (26-74) years, 13 (0.1-40) years at repair) and 20 healthy controls were examined with 24-h ambulatory blood pressure monitoring, echocardiography, vasoactive hormone levels and magnetic resonance of the thoracic aorta. Forty-one patients (36%) were taking antihypertensives (28 RAAS inhibitors). Fifty-one had mean 24-h blood pressures >130/80 mm Hg. Hypertension was not associated with age at repair (P=0.257). Patients had higher PP and LV mass compared with controls (52±11 vs. 45±5 mm Hg and 221±71 vs. 154±55 g, respectively; both Pcoarctation have increased PP and LV mass compared with controls. PP increased with increasing recoarctation. Hypertension was present also in the absence of recoarctation. These changes could not be explained by abnormal activation of the RAAS.

  15. The influence of renin angiotensin aldosterone system blockers on asymmetric dimethylarginine levels in patients with chronic glomerulonephritis

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    Heleniak Zbigniew

    2016-12-01

    Full Text Available Endothelial dysfunction could be related to the limited availability of nitric oxide (NO. NO is synthesized with the participation of an NO synthase whose activity is inhibited by asymmetric dimethylarginine (ADMA. The synthesis of ADMA is exacerbated by oxidative stress, and several studies have shown the efficacy of drugs acting on the renin-angiotensin-aldosterone system (RAAS (converting enzyme inhibitors and angiotensin II receptor antagonists in reducing the level of ADMA. The probable mechanism of drug action is a reduction of oxidative stress through a decrease of angiotensin II formation. The aim of this study was to assess the influence of RAAS blockers on the plasma concentration of ADMA in patients with chronic glomerulonephritis (ChGN. The study included 37 patients, placed into group A and group B, depending on the treatment. Both groups were treated with RAAS blockers. In group B, immunosuppressive drugs were additionally administered. The control visits were at the 0, 6 and 12 months of observation. In both the studied groups (A+B, a significant reduction of ADMA (0.77 vs 0.4 μmol/l; p<0.05 was noticed. In patients suffering from ChGN, the use of RAAS blockers resulted in a significant decrease of plasma ADMA concentration, independently of immunosupressive treatment.

  16. 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

  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 and hypothalamic-pituitary-adrenal axis in hospitalized newborn foals.

    Science.gov (United States)

    Dembek, K A; Onasch, K; Hurcombe, S D A; MacGillivray, K C; Slovis, N M; Barr, B S; Reed, S M; Toribio, R E

    2013-01-01

    The renin-angiotensin-aldosterone system (RAAS) and hypothalamic-pituitary-adrenal axis (HPAA) and their interactions during illness and hypoperfusion are important to maintain organ function. HPAA dysfunction and relative adrenal insufficiency (RAI) are common in septic foals. Information is lacking on the RAAS and mineralocorticoid response in the context of RAI in newborn sick foals. To investigate the RAAS, as well as HPAA factors that interact with the RAAS, in hospitalized foals, and to determine their association with clinical findings. We hypothesized that critical illness in newborn foals results in RAAS activation, and that inappropriately low aldosterone concentrations are part of the RAI syndrome of critically ill foals. A total of 167 foals ≤3 days of age: 133 hospitalized (74 septic, 59 sick nonseptic) and 34 healthy foals. Prospective, multicenter, cross-sectional study. Blood samples were collected on admission. Plasma renin activity (PRA) and angiotensin-II (ANG-II), aldosterone, ACTH, and cortisol concentrations were measured in all foals. ANG-II, aldosterone, ACTH, and cortisol concentrations as well as ACTH/aldosterone and ACTH/cortisol ratios were higher in septic foals compared with healthy foals (P < .05). No difference in PRA between groups was found. High serum potassium and low serum chloride concentrations were associated with hyperaldosteronemia in septic foals. RAAS activation in critically ill foals is characterized by increased ANG-II and aldosterone concentrations. Inappropriately low cortisol and aldosterone concentrations defined as high ACTH/cortisol and ACTH/aldosterone ratios in septic foals suggest that RAI is not restricted to the zona fasciculata in critically ill newborn foals. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  19. The blockade of renin-angiotensin-aldosterone system in hemodialysis patients to control hypertension and prevent cardiovascular disease: optimal pharmacotherapy.

    Science.gov (United States)

    Morishita, Yoshiyuki; Kusano, Eiji

    2011-10-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in hemodialysis (HD) patients. Hypertension (HT) is a major risk factor for CVD. The renin-angiotensin-aldosterone system (RAAS) plays pivotal roles in the pathogenesis of HT in HD patients. Previous studies suggested that the blockade of RAAS may be effective to control blood pressure (BP) and to prevent CVD in HD patients. A certain level of preventive effects against CVD by RAAS blockade in HD patients has been reported independently from a BP lowering effect. This review focuses on the effect of blocking RAAS in HD patients for the control of HT and the prevention of CVD.

  20. Angiotensin II reactivation and aldosterone escape phenomena in renin-angiotensin-aldosterone system blockade: is oral renin inhibition the solution?

    Science.gov (United States)

    Athyros, Vasilios G; Mikhailidis, Dimitri P; Kakafika, Anna I; Tziomalos, Konstantinos; Karagiannis, Asterios

    2007-04-01

    This editorial considers the use of the first selective oral renin inhibitor, aliskiren, in reducing angiotensin (Ang) II reactivation or aldosterone (ALDO) escape during renin-angiotensin-aldosterone system (RAAS) inhibition. RAAS blockade with angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor AT(1) blockers (ARBs) is very useful for the treatment of arterial hypertension, chronic heart failure (CHF), atherosclerosis and diabetes. 'Ang II reactivation' and 'ALDO escape' or 'breakthrough' have been observed during either ACEI or ARB treatment, and may attenuate the clinical benefit of RAAS blockade. Renin and Ang I accumulate during ACE inhibition, and might overcome the ability of an ACEI to effectively suppress ACE activity. There is also data suggesting that 30 - 40% of Ang II formation in the healthy human during RAAS activation is formed via renin-dependent, but ACE-independent, pathways. Moreover, ACE gene polymorphisms contribute to the modulation and adequacy of the neurohormonal response to long-term ACE inhibition, at least in patients with CHF (up to 45% of CHF patients have elevated Ang II levels despite the long-term use of an ACEI) or diabetes. The reactivated Ang II promotes ALDO secretion and sodium reabsorption. ALDO breakthrough also occurs during long-term ARB therapy, mainly by an AT(2)-dependent mechanism. This was related to target-organ damage in animal models. Oral renin inhibition with aliskiren has showed excellent efficacy and safety in the treatment of hypertension. Aliskiren can be co-administered with ACEIs, ARBs or hydrochlorothiazide. Furthermore, there is evidence suggesting that aliskiren reduces Ang II reactivation in ACE inhibition and ALDO escape during treatment with an ACEI or an ARB, at least to the degree that this is associated with the RAAS. For RAAS-independent ALDO production, the combination of aliskiren with eplerenone might prove useful.

  1. 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

    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. W

  2. 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

    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. W

  3. 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.

  4. Varying patterns of the antihypertensive and antialbuminuric response to higher doses of renin-angiotensin-aldosterone system blockade in albuminuric hypertensive type 2 diabetes mellitus patients

    DEFF Research Database (Denmark)

    Weir, Matthew R; Hollenberg, Norman K; Remuzzi, Giuseppe;

    2011-01-01

    In patients with type 2 diabetes mellitus (T2DM), blocking of the renin-angiotensin-aldosterone system (RAAS) has demonstrated efficacy in lowering blood pressure (BP) and urinary albumin excretion rate (UAER). Nonetheless, not all patients successfully respond to RAAS blockade with a reduction i...

  5. Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion.

    Science.gov (United States)

    Qi, Ying; Wang, Xiaojing; Rose, Kristie L; MacDonald, W Hayes; Zhang, Bing; Schey, Kevin L; Luther, James M

    2016-02-01

    Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry-based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112-122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112-122] concentration may provide a useful biomarker of ENaC activation in future clinical studies.

  6. 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.

  7. A systematic review of the role of renin angiotensin aldosterone system genes in diabetes mellitus, diabetic retinopathy and diabetic neuropathy

    Directory of Open Access Journals (Sweden)

    Zohreh Rahimi

    2014-01-01

    Full Text Available Background: The renin angiotensin aldosterone system (RAAS plays a vital role in regulating glucose metabolism and blood pressure, electrolyte and fluid homeostasis. The aim of this systematic review is to assess the association of the RAAS genes with diabetes mellitus (DM and its complications of retinopathy, neuropathy and cardiovascular disease (CVD. Materials and Methods: The relevant English-language studies were identified using the key words of DM, type 1 diabetes mellitus (T1DM, T2DM, renin angiotensin aldosterone polymorphisms or genotypes and RAAS from the search engines of MEDLINE/PubMed, and Scopus from January 1, 1995 to July 30, 2014. Inclusion criteria for selecting relevant studies were reporting the role of RAAS gene variants in the pathogenesis of T1DM or T2DM, diabetic retinopathy (DR, diabetic neuropathy and cardiovascular complication of DM. Results: The reviewers identified 204 studies of which 73 were eligible for inclusion in the present systematic review. The review indicates the angiotensinogen (AGT M235T polymorphism might not affect the risk of DM. The role of angiotensin converting enzyme insertion/deletion (ACE I/D and angiotensin II type 1 receptor gene (AT1R A1166C polymorphisms in the pathogenesis of DM could not be established. Studies indicate the absence of an association between three polymorphisms of AGT M235T, ACE I/D and AT1R A1166C and DR in DM patients. A protective role for ACE II genotype against diabetic peripheral neuropathy has been suggested. Also, the ACE I/D polymorphism might be associated with the risk of CVD in DM patients. Conclusion: More studies with adequate sample size that investigate the influence of all RAAS gene variants together on the risk of DM and its complications are necessary to provide a more clear picture of the RAAS genes polymorphisms involvement in the pathogenesis of DM and its complications.

  8. Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system.

    Science.gov (United States)

    Toh, Sengwee; Reichman, Marsha E; Houstoun, Monika; Ross Southworth, Mary; Ding, Xiao; Hernandez, Adrian F; Levenson, Mark; Li, Lingling; McCloskey, Carolyn; Shoaibi, Azadeh; Wu, Eileen; Zornberg, Gwen; Hennessy, Sean

    2012-11-12

    Although certain drugs that target the renin- angiotensin-aldosterone system are linked to an increased risk for angioedema, data on their absolute and comparative risks are limited. We assessed the risk for angioedema associated with the use of angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and the direct renin inhibitor aliskiren. We conducted a retrospective, observational, inception cohort study of patients 18 years or older from 17 health plans participating in the Mini-Sentinel program who had initiated the use of an ACEI (n = 1 845 138), an ARB (n = 467 313), aliskiren (n = 4867), or a β-blocker (n = 1 592 278) between January 1, 2001, and December 31, 2010. We calculated the cumulative incidence and incidence rate of angioedema during a maximal 365-day follow-up period. Using β-blockers as a reference and a propensity score approach, we estimated the hazard ratios of angioedema separately for ACEIs, ARBs, and aliskiren, adjusting for age, sex, history of allergic reactions, diabetes mellitus, heart failure, or ischemic heart disease, and the use of prescription nonsteroidal anti-inflammatory drugs. A total of 4511 angioedema events (3301 for ACEIs, 288 for ARBs, 7 for aliskiren, and 915 for β-blockers) were observed during the follow-up period. The cumulative incidences per 1000 persons were 1.79 (95% CI, 1.73-1.85) cases for ACEIs, 0.62 (95% CI, 0.55-0.69) cases for ARBs, 1.44 (95% CI, 0.58-2.96) cases for aliskiren, and 0.58 (95% CI, 0.54-0.61) cases for β-blockers. The incidence rates per 1000 person-years were 4.38 (95% CI, 4.24-4.54) cases for ACEIs, 1.66 (95% CI, 1.47-1.86) cases for ARBs, 4.67 (95% CI, 1.88-9.63) cases for aliskiren, and 1.67 (95% CI, 1.56-1.78) cases for β-blockers. Compared with the use of β-blockers, the adjusted hazard ratios were 3.04 (95% CI, 2.81-3.27) for ACEIs, 1.16 (95% CI, 1.00-1.34) for ARBs, and 2.85 (95% CI, 1.34-6.04) for aliskiren. Compared with β-blockers, ACEIs or

  9. Renoprotective effect of renin-angiotensin-aldosterone system blockade in patients with predialysis advanced chronic kidney disease, hypertension, and anemia.

    Science.gov (United States)

    Hsu, Ta-Wei; Liu, Jia-Sin; Hung, Szu-Chun; Kuo, Ko-Lin; Chang, Yu-Kang; Chen, Yu-Chi; Hsu, Chih-Cheng; Tarng, Der-Cherng

    2014-03-01

    The benefit of using a renin-angiotensin-aldosterone system blocker such as an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) for patients with advanced chronic kidney disease (CKD) remains undetermined. To assess the effectiveness and safety of ACEI/ARB use for advanced predialysis CKD in patients with hypertension and anemia. DESIGN Prospective cohort study. Taiwan. From January 1, 2000, through June 30, 2009, we selected 28 497 hypertensive adult patients with CKD. Serum creatinine levels were greater than 6 mg/dL, hematocrit levels were less than 28%, and patients were treated with erythropoiesis-stimulating agents. Users (n = 14,117) and nonusers (n = 14,380) of ACEIs/ARBs. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) for commencement of long-term dialysis and all-cause mortality for ACRI/ARB users vs nonusers. In a median follow-up of 7 months, 20,152 patients (70.7%) required long-term dialysis and 5696 (20.0%) died before progression to end-stage renal disease requiring dialysis. Use of ACEIs/ARBs was associated with a lower risk for long-term dialysis (HR, 0.94 [95% CI, 0.91-0.97]) and the composite outcome of long-term dialysis or death (0.94 [0.92-0.97]). The renal benefit of ACEI/ARB use was consistent across most patient subgroups, as was that of ACEI or ARB monotherapy. Compared with nonusers, the ACEI/ARB users had a higher hyperkalemia-associated hospitalization rate, but the risk of predialysis mortality caused by hyperkalemia was not significantly increased (HR, 1.03 [95% CI, 0.92-1.16]; P = .30). Patients with stable hypertension and advanced CKD who receive therapy with ACEIs/ARBs exhibit an association with lower risk for long-term dialysis or death by 6%. This benefit does not increase the risk of all-cause mortality.

  10. 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 Hald; Ovesen, Per; Hansen, Mie R

    2016-01-01

    It was hypothesized that primary renal sodium retention blunted the reactivity of the renin-angiotensin-aldosterone system to changes in salt intake in preeclampsia (PE). A randomized, cross-over, double-blinded, dietary intervention design was used to measure the effects of salt tablets or placebo...... 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....

  11. 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.

  12. 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.

    2016-01-01

    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. PMID:27347925

  13. Chronobiology of the renin-angiotensin-aldosterone system in dogs: relation to blood pressure and renal physiology.

    Science.gov (United States)

    Mochel, Jonathan P; Fink, Martin; Peyrou, Mathieu; Desevaux, Cyril; Deurinck, Mark; Giraudel, Jérôme M; Danhof, Meindert

    2013-11-01

    The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the regulation of blood pressure and volume homeostasis. Its contribution to the development of cardiovascular diseases has long been recognized. Extensive literature has shown that peptides of the RAAS oscillate with a circadian periodicity in humans, under strong influence of posture, sleep, and age. Although observations of time-variant changes in the renin cascade are available in dogs, no detailed chronobiological investigation has been conducted so far. The present studies were designed to explore the circadian variations of plasma renin activity (RA) and urinary aldosterone-to-creatinine ratio (UA:C) in relation to blood pressure (BP), sodium (UNa, UNa,fe), and potassium (UK, UK,fe) renal handling. Data derived from intensive blood and urine sampling, as well as continuous BP monitoring, were collected throughout a 24-h time period, and analyzed by means of nonlinear mixed-effects models. Differences between the geometric means of day and night observations were compared by parametric statistics. Our results show that variables of the renin cascade, BP, and urinary electrolytes oscillate with significant day-night differences in dogs. An approximately 2-fold (1.6-3.2-fold) change between the average day and night measurements was found for RA (p chronobiology of the renin cascade.

  14. The link between the renin-angiotensin-aldosterone system and renal injury in obesity and the metabolic syndrome.

    Science.gov (United States)

    Thethi, Tina; Kamiyama, Masumi; Kobori, Hiroyuki

    2012-04-01

    Obesity is a risk factor for type 2 diabetes mellitus (DM) and is associated with chronic kidney disease. Activation of the renin-angiotensin-aldosterone system (RAAS) is common in obesity. The RAAS is an important mediator of hypertension. Mechanisms involved in activation of the RAAS in obesity include sympathetic stimulation, synthesis of adipokines in the RAAS by visceral fat, and hemodynamic alterations. The RAAS is known for its role in regulating blood pressure and fluid and electrolyte homeostasis. The role of local/tissue RAAS in specific tissues has been a focus of research. Urinary angiotensinogen (UAGT) provides a specific index of the intrarenal RAAS. Investigators have demonstrated that sex steroids can modulate the expression and activity of the different components of the intrarenal RAAS and other tissues. Our data suggest that obese women without DM and hypertension have significantly higher levels of UAGT than their male counterparts. These differences existed without any background difference in the ratio of microalbumin to creatinine in the urine or the estimated glomerular filtration rate, raising a question about the importance of baseline gender differences in the endogenous RAAS in the clinical spectrum of cardiovascular diseases and the potential utility of UAGT as a marker of the intrarenal RAAS. Animal studies have demonstrated that modifying the amount of angiotensin, the biologically active component of the RAAS, directly influences body weight and adiposity. This article reviews the role of the RAAS in renal injury seen in obesity and the metabolic syndrome.

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

    Science.gov (United States)

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

    2012-10-01

    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 evidence has identified an imbalance of proangiogenic and anti-angiogenic proteins as a key factor in the development of preeclampsia. Furthermore, more attention has been recently addressed to the renin-angiotensin aldosterone system (RAAS), to provide understanding on the hypertension of preeclampsia. The imbalance of the RAAS and the imbalance between angiogenic and anti-angiogenic factors, which may be both common to preeclampsia and chronic kidney disease (CKD), might explain why a history of preeclampsia predisposes women to develop CKD. In this review, we briefly describe the characteristics of preeclampsia with a focus on the mechanisms of angiogenesis and the RAAS and its role in the pathogenesis of preeclampsia. Our main focus will be on the intriguing association between preeclampsia and the subsequent increased risk of developing CKD and on the potential mechanisms by which the risk of CKD is elevated in women with a history of preeclampsia.

  16. No evidence for association between the renin-angiotensin-aldosterone system and otosclerosis in a large Belgian-Dutch population.

    NARCIS (Netherlands)

    Schrauwen, I.; Thys, M.; Straeten, K. van der; Fransen, E.; Ealy, M.; Cremers, C.W.R.J.; Dhooge, I.J.; Heyning, P. van de; Offeciers, E.E.; Smith, R.J.; Camp, G. van

    2009-01-01

    HYPOTHESIS/BACKGROUND: Otosclerosis is a frequent cause of hearing impairment in the Caucasian population and is characterized by abnormal bone remodeling of the otic capsule. Associations with several genes have been reported, and recently, an association between the renin-angiotensin-aldosterone

  17. Association between polymorphisms in the renin-angiotensin-aldosterone system genes and essential hypertension in the Han Chinese population.

    Directory of Open Access Journals (Sweden)

    Lindan Ji

    Full Text Available BACKGROUND: Renin-angiotensin-aldosterone system (RAAS is the most important endocrine blood pressure control mechanism in our body, genes encoding components of this system have been strong candidates for the investigation of the genetic basis of hypertension. However, previous studies mainly focused on limited polymorphisms, thus we carried out a case-control study in the Han Chinese population to systemically investigate the association between polymorphisms in the RAAS genes and essential hypertension. METHODS: 905 essential hypertensive cases and 905 normotensive controls were recruited based on stringent inclusion and exclusion criteria. All 41 tagSNPs within RAAS genes were retrieved from HapMap, and the genotyping was performed using the GenomeLab SNPstream Genotyping System. Logistic regression analysis, Multifactor dimensionality reduction (MDR, stratified analysis and crossover analysis were used to identify and characterize interactions among the SNPs and the non-genetic factors. RESULTS: Serum levels of total cholesterol (TC and triglyceride (TG, and body mass index (BMI were significantly higher in the hypertensive group than in the control group. Of 41 SNPs genotyped, rs3789678 and rs2493132 within AGT, rs4305 within ACE, rs275645 within AGTR1, rs3802230 and rs10086846 within CYP11B2 were shown to associate with hypertension. The MDR analysis demonstrated that the interaction between BMI and rs4305 increased the susceptibility to hypertension. Crossover analysis and stratified analysis further indicated that BMI has a major effect, and rs4305 has a minor effect. CONCLUSION: These novel findings indicated that together with non-genetic factors, these genetic variants in the RAAS may play an important role in determining an individual's susceptibility to hypertension in the Han Chinese.

  18. Ovariectomy modify local renin-angiotensin-aldosterone system gene expressions in the heart of ApoE (-/-) mice.

    Science.gov (United States)

    Borges, Celina Carvalho; Penna-de-Carvalho, Aline; Medeiros Junior, Jorge L; Aguila, Marcia Barbosa; Mandarim-de-Lacerda, Carlos A

    2017-10-04

    The evaluation of the local Renin-Angiotensin-Aldosterone system (RAAS) gene expressions in the heart of ovariectomized (OVX) apolipoprotein E deficient mice (ApoE). Four-months old C57BL/6 female mice (wild-type, wt, n=20), and ApoE female mice (n=20), were submitted to OVX or a surgical procedure without ovary removal (SHAM) and formed four groups (n=10/group): SHAM/wt, SHAM/ApoE, OVX/wt, and OVX/ApoE. OVX led to greater body mass, plasma triglycerides (TG) and total cholesterol, and resulted in insulin resistance and altered RAAS gene expressions in the heart tissue. The gene expression of angiotensin-converting enzyme (ACE)-2 was lower in OVX/wt than in SHAM/wt (P=0.0004), Mas receptor (MASr) was lower in OVX/wt compared to SHAM/wt (P<0.0001). Also, angiotensin II receptor type 1 (AT1r) was higher in OVX/wt than in SHAM/wt (P=0.0229), and AT2r was lower in OVX/wt than in SHAM/wt (P=0.0121). OVX and ApoE deficiency showed interaction potentializing the insulin resistance, increasing TG levels and altering ACE and MASr gene expressions. ACE gene expression was higher in OVX/ApoE than in OVX/wt (P<0.0001), and MASr gene expression was lower in OVX/ApoE than in OVX/wt (P<0.0001). The impact of OVX on local RAAS cascade in the heart of ApoE deficient animals, besides the metabolic changes culminating with insulin resistance, involves an upregulation of renin, ACE, and AT1r gene expressions. The findings may contribute to clarify the mechanisms of development of postmenopausal hypertension and the link between RAAS and apolipoprotein E. Copyright © 2017. Published by Elsevier Inc.

  19. 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.

  20. Effects of renin-angiotensin-aldosterone system blockade on chlorhexidine gluconate-induced sclerosing encapsulated peritonitis in rats.

    Science.gov (United States)

    Koçak, Gülay; Azak, Alper; Astarcı, Hesna Müzeyyen; Huddam, Bülent; Karaca, Gökhan; Ceri, Mevlüt; Can, Murat; Sert, Mehmet; Duranay, Murat

    2012-02-01

    Sclerosing encapsulated peritonitis (SEP) is a rare complication of long term peritoneal dialysis. Renin-angiotensin-aldosterone system (RAAS) may play a role in the development of peritoneal fibrosis in CAPD patients. We aimed to evaluate the effect of aliskiren, valsartan, and aliskiren + valsartan therapy on SEP. The study included 30 Wistar albino rats which were divided into five groups: I (Control) SF solution i.p.; II (CG group) chlorhexidine gluconate i.p.; III aliskiren oral plus CG i.p.; IV valsartan oral plus CG i.p.; and V aliskiren oral, valsartan oral and CG i.p. On the twenty-first day, all of the rats were sacrificed. All of the groups were analyzed in terms of peritoneal thickness, degree of inflammation, vasculopathy, neovascularization and fibrosis. Also, the parietal peritoneal tissue samples were evaluated for matrix metalloproteinase 2 (MMP-2) using the ELISA method. Peritoneal thickness and fibrosis scores were lower in the valsartan group compared to the CG group (P 0.05). Tissue MMP-2 levels were significantly higher in the CG group compared other groups (P < 0.05). There were no statistically significant differences between the aliskiren, valsartan and aliskiren + valsartan groups according to the tissue MMP-2 levels. Due to the antifibrotic properties of valsartan, it is thought to be a possible choice to prevent SEP development. We found no positive impact of aliskiren or aliskiren + valsartan combination compared to valsartan alone. © 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.

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

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    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.

  2. 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 (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 in preeclampsia involves constrictor AT2 receptors.

  3. Familial Analysis of Epistatic and Sex-Dependent Association of Genes of the Renin-Angiotensin-Aldosterone System and Blood Pressure.

    Science.gov (United States)

    Scurrah, Katrina J; Lamantia, Angela; Ellis, Justine A; Harrap, Stephen B

    2017-06-01

    Renin-angiotensin-aldosterone system genes have been inconsistently associated with blood pressure, possibly because of unrecognized influences of sex-dependent genetic effects or gene-gene interactions (epistasis). We tested association of systolic blood pressure with single-nucleotide polymorphisms (SNPs) at renin (REN), angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), and aldosterone synthase (CYP11B2), including sex-SNP or SNP-SNP interactions. Eighty-eight tagSNPs were tested in 2872 white individuals in 809 pedigrees from the Victorian Family Heart Study using variance components models. Three SNPs (rs8075924 and rs4277404 at ACE and rs12721297 at AGTR1) were individually associated with lower systolic blood pressure with significant (Ppressure. Four SNP pairs were at the same gene (2 for REN, 1 for AGT, and 1 for AGTR1). The SNP rs3097 at CYP11B2 was represented in 5 separate pairs. SNPs at key renin-angiotensin-aldosterone system genes associate with systolic blood pressure individually in both sexes, individually in one sex only and only when combined with another SNP. Analyses that incorporate sex-dependent and epistatic effects could reconcile past inconsistencies and account for some of the missing heritability of blood pressure and are generally relevant to SNP association studies for any phenotype. © 2017 American Heart Association, Inc.

  4. A Detailed Physiologically Based Model to Simulate the Pharmacokinetics and Hormonal Pharmacodynamics of Enalapril on the Circulating Endocrine Renin-Angiotensin-Aldosterone System

    Science.gov (United States)

    Claassen, Karina; Willmann, Stefan; Eissing, Thomas; Preusser, Tobias; Block, Michael

    2013-01-01

    The renin-angiotensin-aldosterone system (RAAS) plays a key role in the pathogenesis of cardiovascular disorders including hypertension and is one of the most important targets for drugs. A whole body physiologically based pharmacokinetic (wb PBPK) model integrating this hormone circulation system and its inhibition can be used to explore the influence of drugs that interfere with this system, and thus to improve the understanding of interactions between drugs and the target system. In this study, we describe the development of a mechanistic RAAS model and exemplify drug action by a simulation of enalapril administration. Enalapril and its metabolite enalaprilat are potent inhibitors of the angiotensin-converting-enzyme (ACE). To this end, a coupled dynamic parent-metabolite PBPK model was developed and linked with the RAAS model that consists of seven coupled PBPK models for aldosterone, ACE, angiotensin 1, angiotensin 2, angiotensin 2 receptor type 1, renin, and prorenin. The results indicate that the model represents the interactions in the RAAS in response to the pharmacokinetics (PK) and pharmacodynamics (PD) of enalapril and enalaprilat in an accurate manner. The full set of RAAS-hormone profiles and interactions are consistently described at pre- and post-administration steady state as well as during their dynamic transition and show a good agreement with literature data. The model allows a simultaneous representation of the parent-metabolite conversion to the active form as well as the effect of the drug on the hormone levels, offering a detailed mechanistic insight into the hormone cascade and its inhibition. This model constitutes a first major step to establish a PBPK-PD-model including the PK and the mode of action (MoA) of a drug acting on a dynamic RAAS that can be further used to link to clinical endpoints such as blood pressure. PMID:23404365

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

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo J.

    2011-01-01

    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 therapie

  6. The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

    Directory of Open Access Journals (Sweden)

    Maricica Pacurari

    2014-01-01

    Full Text Available The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNFα, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS’s role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors.

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

    Directory of Open Access Journals (Sweden)

    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

  8. Chronic vasodilation increases renal medullary PDE5A and α-ENaC through independent renin-angiotensin-aldosterone system pathways.

    Science.gov (United States)

    West, Crystal A; Shaw, Stefan; Sasser, Jennifer M; Fekete, Andrea; Alexander, Tyler; Cunningham, Mark W; Masilamani, Shyama M E; Baylis, Chris

    2013-11-15

    We have previously observed that many of the renal and hemodynamic adaptations seen in normal pregnancy can be induced in virgin female rats by chronic systemic vasodilation. Fourteen-day vasodilation with sodium nitrite or nifedipine (NIF) produced plasma volume expansion (PVE), hemodilution, and increased renal medullary phosphodiesterase 5A (PDE5A) protein. The present study examined the role of the renin-angiotensin-aldosterone system (RAAS) in this mechanism. Virgin females were treated for 14 days with NIF (10 mg·kg(-1)·day(-1) via diet), NIF with spironolactone [SPR; mineralocorticoid receptor (MR) blocker, 200-300 mg·kg(-1)·day(-1) via diet], NIF with losartan [LOS; angiotensin type 1 (AT1) receptor blocker, 20 mg·kg(-1)·day(-1) via diet], enalapril (ENAL; angiotensin-converting enzyme inhibitor, 62.5 mg/l via water), or vehicle (CON). Mean arterial pressure (MAP) was reduced 7.4 ± 0.5% with NIF, 6.33 ± 0.5% with NIF + SPR, 13.3 ± 0.9% with NIF + LOS, and 12.0 ± 0.4% with ENAL vs. baseline MAP. Compared with CON (3.6 ± 0.3%), plasma volume factored for body weight was increased by NIF (5.2 ± 0.4%) treatment but not by NIF + SPR (4.3 ± 0.3%), NIF + LOS (3.6 ± 0.1%), or ENAL (4.0 ± 0.3%). NIF increased PDE5A protein abundance in the renal inner medulla, and SPR did not prevent this increase (188 ± 16 and 204 ± 22% of CON, respectively). NIF increased the α-subunit of the epithelial sodium channel (α-ENaC) protein in renal outer (365 ± 44%) and inner (526 ± 83%) medulla, and SPR prevented these changes. There was no change in either PDE5A or α-ENaC abundance vs. CON in rats treated with NIF + LOS or ENAL. These data indicate that the PVE and renal medullary adaptations in response to chronic vasodilation result from RAAS signaling, with increases in PDE5A mediated through AT1 receptor and α-ENaC through the MR.

  9. The Effect of Renin-Angiotensin-Aldosterone System Blockade Medications on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography: A Meta-Analysis.

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    Zhijun Wu

    Full Text Available Contrast-induced nephropathy (CIN is the main complication of contrast media administration (CM in patients undergoing coronary angiography (CAG and percutaneous coronary intervention (PCI. There are inconsistent results in the literature regarding the effect of renin-angiotensin-aldosterone system (RAAS blockers (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs] on CIN. We evaluated the association between the administration of ACEI/ARBs and CIN, as well as the effect of ACEI/ARBs on post-procedural changes in renal function index, in patients undergoing CAG.We searched Pubmed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for relevant studies. The primary search generated 893 potentially relevant articles. A total of 879 studies were excluded because they did not meet the selection criteria. Finally, 14 studies were eligible for inclusion. There were 7,288 patients that received ACEI/ARBs and 8,159 patients that received placebo or naive to ACEI/ARBs in the study. A random or a fixed effect model was used to calculate the pooled odd ratios (ORs.The risk of CIN was significantly increased in the ACEI/ARBs group compared to the control group (OR= 1.50, 95%CI: 1.03-2.18, P =0.03. The magnitude of association was significantly reinforced in the observational studies (OR=1.84, 95%CI 1.19-2.85, P=0.006 but not in the randomized controlled trials (OR=0.88, 95%CI 0.41-1.90 P=0.74. The summary adjusted OR of 4 observational studies was 1.56 (95%CI 1.25-1.94, P<0.0001 and was weaker than the unadjusted OR.Although there is some evidence to suggest that the administration of RAAS blockers was associated with the increased risk of CIN in patients undergoing CAG, the robustness of our study remains weak. The results are based on small observational studies and need further validation.

  10. 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

  11. 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 pla

  12. Atrial fibrillation and arterial hypertension: A common duet with dangerous consequences where the renin angiotensin-aldosterone system plays an important role.

    Science.gov (United States)

    Seccia, Teresa Maria; Caroccia, Brasilina; Muiesan, Maria Lorenza; Rossi, Gian Paolo

    2016-03-01

    Atrial fibrillation (AF) represents the most common sustained cardiac arrhythmia, as it affects 1%-2% of the general population and up to 15% of people over 80 years. High blood pressure, due to its high prevalence in the general population, is by far the most common condition associated with AF, although a variety of diseases, including valvular, coronary heart and metabolic diseases, are held to create the substrate favouring AF. Due to the concomitance of these conditions, it is quite challenging to dissect the precise role of high blood pressure in triggering/causing AF. Hence, even though the intimate association between high blood pressure and AF has been known for decades, the underlying mechanisms remain partially unknown. Accumulating evidences point to a major role of the renin-angiotensin-aldosterone system in inducing cardiac inflammation and fibrosis, and therefore electric and structural atrial and ventricular remodelling, with changes in ions and cell junctions leading to AF development. These evidences are herein reviewed with a particular emphasis to the role of the renin-angiotensin-system aldosterone system.

  13. Changeover Trial of Azilsartan and Olmesartan Comparing Effects on the Renin-Angiotensin-Aldosterone System in Patients with Essential Hypertension after Cardiac Surgery (CHAOS Study).

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    Sezai, Akira; Osaka, Shunji; Yaoita, Hiroko; Arimoto, Munehito; Hata, Hiroaki; Shiono, Motomi; Sakino, Hisakuni

    2016-06-20

    Angiotensin II receptor blockers (ARBs) have been widely used to treat hypertension and large-scale clinical studies have shown various benefits. In this study, we compared olmesartan with azilsartan, the newest ARB. The subjects were outpatients who were clinically stable after cardiac surgery. Sixty patients were randomized to receive either azilsartan or olmesartan for 1 year and were switched to the other drug for the following 1 year. The primary endpoints were the levels of plasma renin activity, angiotensin II, and aldosterone. Home blood pressure exceeded 140/90 mmHg and additional antihypertensive medication was administered to 12 patients (20 episodes) in the azilsartan group versus 4 patients (4 episodes) in the olmesartan group, with the number being significantly higher in the azilsartan group. After 1 year of treatment, both angiotensin II and aldosterone levels were significantly lower in the olmesartan group than the azilsartan group. Left ventricular mass index was also significantly lower in the olmesartan group than the azilsartan group. This study showed that olmesartan reduces angiotensin II and aldosterone levels more effectively than azilsartan. Accordingly, it may be effective in patients with increased renin-angiotensin-aldosterone system activity after cardiac surgery or patients with severe cardiac hypertrophy.

  14. High potassium promotes mutual interaction between (pro)renin receptor and the local renin-angiotensin-aldosterone system in rat inner medullary collecting duct cells.

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    Xu, Chuanming; Fang, Hui; Zhou, Li; Lu, Aihua; Yang, Tianxin

    2016-10-01

    (Pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD) with unclear functional implication. It is not known whether CD PRR is regulated by high potassium (HK). Here, we aimed to investigate the effect of HK on PRR expression and its role in regulation of aldosterone synthesis and release in the CD. In primary rat inner medullary CD cells, HK augmented PRR expression and soluble PPR (sPRR) release in a time- and dose-dependent manner, which was attenuated by PRR small interfering RNA (siRNA), eplerenone, and losartan. HK upregulated aldosterone release in parallel with an increase of CYP11B2 (cytochrome P-450, family 11, subfamily B, polypeptide 2) protein expression and upregulation of medium renin activity, both of which were attenuated by a PRR antagonist PRO20, PRR siRNA, eplerenone, and losartan. Similarly, prorenin upregulated aldosterone release and CYP11B2 expression, both of which were attenuated by PRR siRNA. Interestingly, a recombinant sPRR (sPRR-His) also stimulated aldosterone release and CYP11B2 expression. Taken together, we conclude that HK enhances a local renin-angiotensin-aldosterone system (RAAS), leading to increased PRR expression, which in turn amplifies the response of the RAAS, ultimately contributing to heightened aldosterone release.

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

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    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.

  16. Prolonged fasting increases the response of the renin-angiotensin-aldosterone system, but not vasopressin levels, in postweaned northern elephant seal pups

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    Ortiz, R. M.; Wade, C. E.; Ortiz, C. L.

    2000-01-01

    The 8- to 12-week postweaning fast exhibited by northern elephant seal pups (Mirounga angustirostris) occurs without any apparent deleterious effects on fluid and electrolyte homeostasis. However, during the fast the role of vasopressin (AVP) has been shown to be inconclusive and the involvement of the renin-angiotensin-aldosterone system (RAAS) has yet to be examined. To examine the effects of prolonged fasting on these osmoregulatory hormones, 15 postweaned pups were serially blood-sampled during the first 49 days of their fast. Fasting did not induce significant changes in ionic or osmotic concentrations, suggesting electrolyte homeostasis. Total proteins were reduced by day 21 of fasting and remained depressed, suggesting a lack of dehydration. Aldosterone and plasma renin activity exhibited a correlated, linear increase over the first 49 days of the fast, suggesting an active RAAS. Aldosterone exhibited a parabolic trend over the fast with a peak at day 35, suggesting a shift in the sensitivity of the kidney to aldosterone later in the fast. AVP was elevated at day 49 only, but concentrations were relatively low. RAAS was modified during the postweaning fast in pups and appears to play a significant role in the regulation of electrolyte and, most likely, water homeostasis during this period. Copyright 2000 Academic Press.

  17. 肾素-血管紧张素-醛固酮系统与糖尿病肾病%Renin-angiotensin-aldosterone system and the treatment of diabetic kidney disease

    Institute of Scientific and Technical Information of China (English)

    潘道延; 沈洁

    2015-01-01

    Diabetic nephropathy as a chronic complications of diabetes, its incidence in recent years along with the increasing incidence of diabetes also showed a trend of rising year. Renin-angiotensin aldosterone system activation in the occurrence of diabetic nephropathy development has the extremely important status, use of RAAS inhibitors can significantly control high blood pressure, reduce urine protein, reduce glomerular filtration, and delay the renal interstitial fibrosis. Some large clinical trials have confirmed that inhibiting renin-angiotensin aldosterone system treatment can significantly reduce microalbuminuria and macroalbuminuria in patients with diabetic nephropathy, delay the progress of diabetic nephropathy, and reduce the incidence of end-stage renal disease. But the combined use of RAAS blocker due to its significantly increased adverse events also needs our further research.%糖尿病肾病作为糖尿病的一种慢性并发症,近年来其发病率随着糖尿病的发病率不断上升也呈现逐年上升的趋势。肾素-血管紧张素-醛固酮系统(RAAS)的激活在糖尿病肾病的发生发展中有着极其重要的地位,使用RAAS抑制剂可以明显地控制血压、减少尿蛋白、减轻肾小球高滤过、延缓肾间质纤维化。一些大型的临床试验已经证实抑制RAAS的治疗可以明显减轻糖尿病肾病患者微量白蛋白尿及大量白蛋白尿的产生及发展,延缓糖尿病肾病的进展,减少终末期肾病的发病率。但目前关于联合应用RAAS阻滞剂因其不良事件的明显增加还需要我们进一步探索解决。

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

    Science.gov (United States)

    Pöschke, Antje; Kern, Niklas; Maruyama, Takayuki; Pavenstädt, Hermann; Narumiya, Shuh; Jensen, Boye L; Nüsing, Rolf M

    2012-11-15

    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 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, creatinine clearance, and plasma antidiuretic hormone (ADH) concentration. Following salt restriction, plasma renin and aldosterone concentrations and kidney renin mRNA level rose significantly in EP4(+/+) but not in EP4(-/-) and in wild-type mice treated with EP4 antagonist ONO-AE3-208. In the latter two groups, the low-salt diet caused a significantly greater rise in PGE(2) excretion. Furthermore, mRNA expression for COX-2 and PGE(2) synthetic activity was significantly greater in EP4(-/-) than in EP4(+/+) mice. We conclude that low dietary salt intake induces expression of COX-2 followed by enhanced renal PGE(2) synthesis, which stimulates the renin-angiotensin-aldosterone system by activation of EP4 receptor. Most likely, defects at the step of EP4 receptor block negative feedback mechanisms on the renal COX system, leading to persistently high PGE(2) levels, diuresis, and K(+) loss.

  19. 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.

  20. Polymorphisms in genes of the renin-angiotensin-aldosterone system and renal cell cancer risk: interplay with hypertension and intakes of sodium, potassium and fluid.

    Science.gov (United States)

    Deckers, Ivette A; van den Brandt, Piet A; van Engeland, Manon; van Schooten, Frederik-Jan; Godschalk, Roger W; Keszei, András P; Schouten, Leo J

    2015-03-01

    Hypertension is an established risk factor for renal cell cancer (RCC). The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and is closely linked to hypertension. RAAS additionally influences homeostasis of electrolytes (e.g. sodium and potassium) and fluid. We investigated single nucleotide polymorphisms (SNPs) in RAAS and their interactions with hypertension and intakes of sodium, potassium and fluid regarding RCC risk in the Netherlands Cohort Study (NLCS), which was initiated in 1986 and included 120,852 participants aged 55 to 69 years. Diet and lifestyle were assessed by questionnaires and toenail clippings were collected. Genotyping of toenail DNA was performed using the SEQUENOM® MassARRAY® platform for a literature-based selection of 13 candidate SNPs in seven key RAAS genes. After 20.3 years of follow-up, Cox regression analyses were conducted using a case-cohort approach including 3,583 subcohort members and 503 RCC cases. Two SNPs in AGTR1 were associated with RCC risk. AGTR1_rs1492078 (AA vs. GG) decreased RCC risk [hazard ratio (HR) (95% confidence interval (CI)): 0.70(0.49-1.00)], whereas AGTR1_rs5186 (CC vs. AA) increased RCC risk [HR(95%CI): 1.49(1.08-2.05)]. Associations were stronger in participants with hypertension. The RCC risk for AGT_rs3889728 (AG + AA vs. GG) was modified by hypertension (p interaction = 0.039). SNP-diet interactions were not significant, although HRs suggested interaction between SNPs in ACE and sodium intake. SNPs in AGTR1 and AGT influenced RCC susceptibility, and their effects were modified by hypertension. Sodium intake was differentially associated with RCC risk across genotypes of several SNPs, yet some analyses had probably inadequate power to show significant interaction. Results suggest that RAAS may be a candidate pathway in RCC etiology. © 2014 UICC.

  1. Renin-angiotensin-aldosterone system polymorphisms: a role or a hole in occurrence and long-term prognosis of acute myocardial infarction at young age

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    Piazza Alberto

    2007-05-01

    Full Text Available Abstract Background The renin-angiotensin-aldosterone system (RAAS is involved in the cardiovascular homeostasis as shown by previous studies reporting a positive association between specific RAAS genotypes and an increased risk of myocardial infarction. Anyhow the prognostic role in a long-term follow-up has not been yet investigated. Aim of the study was to evaluate the influence of the most studied RAAS genetic Single Nucleotide Polymorphisms (SNPs on the occurrence and the long-term prognosis of acute myocardial infarction (AMI at young age in an Italian population. Methods The study population consisted of 201 patients and 201 controls, matched for age and sex (mean age 40 ± 4 years; 90.5% males. The most frequent conventional risk factors were smoke (p Results We found a borderline significant association of occurrence of AMI with the ACE D/I polymorphism (DD genotype, 42% in cases vs 31% in controls; p = 0.056. DD genotype remained statistically involved in the incidence of AMI also after adjustment for clinical confounders. On the other hand, during the 9-year follow-up (65 events, including 13 deaths we found a role concerning the AGTR1: the AC heterozygous resulted more represented in the event group (p = 0.016 even if not independent from clinical confounders. Anyhow the Kaplan-Meier event free curves seem to confirm the unfavourable role of this polymorphism. Conclusion Polymorphisms in RAAS genes can be important in the onset of a first AMI in young patients (ACE, CYP11B2 polymorphisms, but not in the disease progression after a long follow-up period. Larger collaborative studies are needed to confirm these results.

  2. Genetic polymorphisms of the renin-angiotensin-aldosterone system in Chinese patients with end-stage renal disease secondary to IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    HUANG Hai-dong; LIN Fu-jun; LI Xin-juan; WANG Li-rui; JIANG Geng-ru

    2010-01-01

    Background Genetic variability in the renin-angiotensin-aldosterone system may modify renal responses to injury and disease progression. The angiotensin l-converting enzyme (ACE) gene insertion/deletion (l/D), the angiotensinogen (AGT) gene, M235T, the aldosterone synthase (CYP11B2) gene, C-344T, and the angiotensin Ⅱ type 1 receptor (AT1 R)gene, A1166C, have been shown to be associated with IgA nephropathy (IgAN) and its progression. We determined the presence of these polymorphisms in 130 Chinese patients with IgAN, including 47 patients with end-stage renal disease (ESRD) and 120 healthy Chinese subjects, to assess their impact on the susceptibility to disease and the liability of progression to ESRD.Methods Genotyping was performed with DNA isolated from peripheral leucocytes using polymerase chain reaction amplification of the polymorphic sequence, restriction enzyme digestion, and separation and identification of DNA fragments. Clinical data from renal biopsies were collected.Results ACE, AGT, CYP and AT1R genotype distributions were similar in patients with lgAN and in controls. Comparing patients with ESRD (IgAN-ESRD) and those without ESRD (IgAN-non ESRD), there was a significant increase only in the ACE DD genotype (P <0.05) among the four gene polymorphisms. There was significant dominance of the male (P <0.05), more marked hypertension (P <0.01), proteinuria (P <0.01) and increased serum creatinine during renal biopsy (P <0.01) in the IgAN-ESRD group.Conclusion Among the ACE, AGT, AT1R and CYP gene polymorphisms, only the DD genotype may predispose the individual to increased risk of progression to ESRD in the Chinese population.

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

    Energy Technology Data Exchange (ETDEWEB)

    Slavnov, V.N.; Yakovlev, A.A.; Yugrinov, O.G.; Gandzha, T.I. (Kievskij Nauchno-Issledovatel' skij Inst. Ehndokrinologii i Obmena Veshchestv (Ukrainian SSR))

    1983-02-01

    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.

  4. [Left-ventricular hypertrophy as a cardiac risk factor: role of the renin-angiotensin-aldosterone system].

    Science.gov (United States)

    Erne, P

    1996-02-20

    Left-ventricular hypertrophy is the result of cardiac adaptation to global or regional overstress and represents an important cardiovascular risk factor, increasing the risk for development of congestive heart failure and incidence of sudden death. This review describes the pathophysiological and biochemical mechanisms involved in the development of left-ventricular hypertrophy and cardiac fibrosis with particular emphasis on the role of angiotensin II and aldosterone. Central to the cascade of cardiac fibrosis is the increased production or reduced degradation of collagen proteins in fibroblasts. Collagen proteins are proteins needed for the alignment of cellular compartments and the development of forces, contraction and relaxation of the heart. If overexpressed, an important rise of wall stiffness is observed in addition to a reduced capacity to provide oxygen to the cardiac tissue. This latter explains why in areas of histologically hypertrophied heart muscle atrophied muscle cells are observed. The characterization of the second-messenger systems involved in the regulation of cardiac cells as well as the identification of angiotensin-II receptor subtype and angiotensin IV is described. Both of these receptors are present on cardiac fibroblasts and stimulate these to collagen production, which can be inhibited by antagonists or the generation of angiotensin II by ACE inhibitors. In some forms of left-ventricular hypertrophy and in patients with congestive heart failure in addition to elevated angiotensin-II levels, increased aldosterone levels are observed. Aldosterone raises upon stimulation by angiotensin II and upon reduction of angiotensin-II generation subsequent to ACE inhibition through an escape mechanism. The contribution of aldosterone to left-ventricular hypertrophy and cardiac fibrosis can be prevented and reduced by the administration of its antagonist, spironolactone. Further and larger clinical trials are needed and in progress to evaluate if the

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

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    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

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

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    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, pproteinuria 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, pproteinuria (1.9±1.4 to 0.8±0.5, pproteinuria was higher than 50% in 22 (68.8%) cases in obese patients and in 33 (84.6%) cases in non-obese group. Renal function remained stable in both groups during the follow-up. Nine patients (28.1%) in

  7. Correlation between Diabetic Nephropathy and Renin-angiotensin-aldosterone System%糖尿病肾病与肾素-血管紧张素-醛固酮系统的关系

    Institute of Scientific and Technical Information of China (English)

    曹丹

    2012-01-01

    Diabetic nephropathy( diabetic kidney disease )is defined as a rise in urinary albumin excretion rate, often associated with an increase in blood pressure, and typically with concomitant retinopathy. It is characterized firstly by albuminuria and then by a progressive decline in glomerular filtration rate, eventually resulting in end-stage renal disease( ESRD ). A diabetic milieu is required for the diabetic glomerular lesion to develop, and renin-angiotensin-aldosterone system is an endocrine system with complex physiological functions, playing an important role in prevention, development and progression of diabetic nephropathy. Using drugs that block the renin-angiotensin-aldosterone system are effective strategies for preventing the development of diabetic nephropathy delaying the progression to more advanced stages of nephropathy.%糖尿病肾病是一种尿蛋白排泄率增加,通常伴有血压升高和典型的视网膜病变的疾病.这种疾病的特点首先是出现蛋白尿,继而肾小球滤过率进行性下降,最终导致终末期肾脏病.糖尿病环境对糖尿病患者肾小球的损伤甚至加重是必要的,肾素-血管紧张素-醛固酮系统是生理功能颇为复杂的内分泌系统,对糖尿病肾病的预防、发生、发展有重要作用.肾素-血管紧张素-醛固酮系统阻断剂药物的应用在阻止糖尿病肾病的进展以及延缓发展到晚期肾脏病阶段是有效的方法.

  8. Advance of research on application of renin-angiotensin-aldosterone system blockers in elderly patients with chronic kidney disease%RAAS阻滞剂在老年慢性肾脏病中应用的研究进展

    Institute of Scientific and Technical Information of China (English)

    张琪; 倪兆慧

    2014-01-01

    全球老龄人(年龄≥65岁)所占的人口比例正逐步上升。老年人由于其特殊的生理状态更易被一些慢性病如,高血压、糖尿病、慢性肾脏病( CKD)所困扰。肾素-血管紧张素-醛固酮系统( RAAS)的过分活跃可导致高血压、心血管事件及CKD的发生。因此,针对RAAS的治疗具有可行性。但老年患者在使用RAAS阻滞剂[主要包括血管紧张素转换酶抑制剂( ACEI)、血管紧张素受体阻滞剂( ARB)、肾素抑制剂、醛固酮拮抗剂]类药物时更易出现肾小球滤过率( GFR)下降、高钾血症、低血压等不良反应,所以临床使用时,需要特别平衡使用该类药物的利弊。尽管目前对老年人使用RAAS阻滞剂药物有限的研究大多获得了肯定的结论,但是,仍需要更多、更长周期的研究结果来探寻老年CKD患者使用RAAS阻滞剂的疗效和安全性,以及是否确实能减缓CKD的进展。%Theproportionofglobalolderpeople(age≥65years)isgraduallyincreasing.Because of their special physiological state,older people are more easily troubled by some chronic diseases such as hypertension,diabetes,and chronic kidney disease( CKD). Overactivity of renin-angiotensin-aldosterone system( RAAS)can lead to hypertension,cardiovascular events,as well as CKD. Therefore,the treatment targeting RAAS is feasible. However,while using RAAS blockers including angiotensin converting enzyme inhibitors( ACEI),angiotensin receptor blockers( ARB),renin inhibitors,and aldosterone antagonists, elderly patients are more likely to be subjected to decrease of glomerular filtration rate ( GFR ), hyperkalemia,and hypotension,etc,indicating that it is specially required to weigh the pros and cons before clinical use of such drugs. Although most limited researches on efficacy of RAAS blocker drugs in elderly patients obtained positive conclusions,more long-term studies are still needed to explore the therapeutic efficacy

  9. The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin-angiotensin-aldosterone system, oxidative stress and endogenous digitalis in the brain.

    Science.gov (United States)

    Takahashi, Hakuo; Yoshika, Masamichi; Komiyama, Yutaka; Nishimura, Masato

    2011-11-01

    The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood pressure. The turnover rate of these materials increases with increasing sodium intake. As intracerebroventricular injection of ouabain increases blood pressure via sympathetic activation, an endogenous digitalis-like factor (EDLF) was thought to regulate cardiovascular system-related functions in the brain, particularly after sodium loading. Experiments conducted mainly in rats revealed that the mechanism of action of ouabain in the brain involves sodium ions, epithelial sodium channels (ENaCs) and the renin-angiotensin-aldosterone system (RAAS), all of which are affected by sodium loading. Rats fed a high-sodium diet develop elevated sodium levels in their cerebrospinal fluid, which activates ENaCs. Activated ENaCs and/or increased intracellular sodium in neurons activate the RAAS; this releases EDLF in the brain, activating the sympathetic nervous system. The RAAS promotes oxidative stress in the brain, further activating the RAAS and augmenting sympathetic outflow. Angiotensin II and aldosterone of peripheral origin act in the brain to activate this cascade, increasing sympathetic outflow and leading to hypertension. Thus, the brain Na(+)-ENaC-RAAS-EDLF axis activates sympathetic outflow and has a crucial role in essential and secondary hypertension. This report provides an overview of the central mechanism underlying hypertension and discusses the use of antihypertensive agents.

  10. Multiple Polymorphisms in the renin- angiotensin-aldosterone system (ACE, CYP11B2, AGTR1) and their contribution to hypertension in African Americans and Latinos in the multiethnic cohort.

    Science.gov (United States)

    Henderson, Sean O; Haiman, Christopher A; Mack, Wendy

    2004-11-01

    When compared with other U.S. populations, African Americans have excess hypertension. Genetic variants in elements of the renin-angiotensin-aldosterone system (RAAS), namely the angiotensin-converting enzyme (ACE), aldosterone synthase (CYP11B2), and angiotensin II type 1 receptor (AGTR1) genes, have been associated with risk of hypertension in some populations. We genotyped the D/I polymorphism in the ACE gene, the C(-344)T polymorphism in the CYP11B2 gene, and the C(-535)T polymorphism in the AGTR1 gene among African American and Latino members of the Multiethnic Cohort Study (MEC) to determine their association with hypertension. We observed no significant increase in the risk of hypertension for either African Americans or Latinos homozygous or heterozygous for the D allele of the ACE gene. Among African Americans we observed carriers of the (-344)T allele of CYP11B2 to be at increased risk of hypertension (versus CC genotype: TC genotype, OR = 1.66 [95% CI: 1.01-2.72]; TT genotype, OR = 1.74 [95% CI: 1.07-2.82]). There was also an increase in risk of hypertension associated with the AGTR1 T allele for African Americans (versus CC genotype: TC genotype, OR = 2.62 [95% CI: 1.46-4.72]; TT genotype, OR = 2.67 [95% CI: 1.51-4.74]). The associations observed with CYP11B2 and AGTR1 genotypes were not observed among Latinos. These data suggest that the (-535)T allele of AGTR1 and (-344)T allele of CYP11B2 may increase hypertension risk among African Americans but not among Latinos. Characterization of the linkage disequilibrium and haplotype patterns in the RAAS pathway genes will be crucial to understanding differences in hypertension susceptibility in these ethnic populations.

  11. 不同亚型库欣综合征患者肾素-血管紧张素-醛固酮系统变化%The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome

    Institute of Scientific and Technical Information of China (English)

    崔佳; 窦京涛; 杨国庆; 臧丽; 金楠; 陈康; 杜锦; 谷伟军; 王先令

    2015-01-01

    Objective Cushing's syndrome is a clinical condition resulting from chronic exposure to excess glucocorticoid.As a consequence,long-term hypercortisolism contributes significantly to the development of systemic disorders by direct and/or indirect effects.The present study was to analyze the changes of renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome on the standard posture test.Methods We retrospectively reviewed 150 patients with histologically confirmed Cushing's syndrome treated at the PLA General Hospital between 2002 and 2014.Among them,128 patients were diagnosed as adreno-cortico-tropic-hormone (ACTH)-independent Cushing's syndrome,and 22 were ACTH-dependent Cushing's syndrome.All patients were undertaken the posture test.Plasma renin activity (PRA),angiotensin Ⅱ,plasma aldosterone concertration (PAC) levels were measured before and after the test.Results Basal plasma PRA [0.5 (0.2,1.3) μg · L-1 · h-1],angiotensin Ⅱ [(48.9 ± 20.1) ng/L] and PAC [(285.0 ± 128.1) pmol/L] levels were within the normal range in supine position.Compared with the subjects with ACTH-independent Cushing's syndrome,the basal PAC levels were higher in subjects with ACTH-dependent Cushing' s syndrome [(348.0 ± 130.4) pmol/L vs (274.2 ± 125.0) pmol/L,P < 0.05].However,the PAC response in subjects with ACTH-dependent Cushing's syndrome [(49.7 ± 26.4)%] was significantly lower than that in those with ACTH-independent Cushing's syndrome [(81.2 ± 69.3) %] upon upright posture stimulation (P < 0.05).There were no statistical significances in PRA and angiotensin Ⅱ levels between the two groups.The basal PAC and PRA levels were positively correlated with ACTH,whereas PAC response was negatively correlated with ACTH.Conclusions The renin-angiotensin-aldosterone-system activity in subjects with Cushing's syndrome was similar to that in normal control.The basal PAC level and its response to upright posture are differently associated with ACTH

  12. 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....

  13. Effect of renin-angiotensin -aldosterone system blockers on myocardial remodeling processes and risk for atrial fibrillation in patients with arterial hypertension

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2014-07-01

    Full Text Available The given review considers the mechanisms underlying the development and maintenance of atrial fibrillations (AF. It is noted that the processes of atrial fibrosis, ion channel remodeling, inflammation, apoptosis, impaired intercellular interactions, and myocardiocyte hypertrophy may give rise to atrial structural and functional changes in AF. The efficacy of angiotensinonverting enzyme inhibitors and angiotensin receptor antagonists is justified in patients with left ventricular systolic dysfunction.

  14. 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.

  15. 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

  16. Sodium restriction on top of renin-angiotensin-aldosterone system blockade increases circulating levels of N-acetyl-seryl-aspartyl-lysyl-proline in chronic kidney disease patients

    NARCIS (Netherlands)

    Kwakernaak, Arjan J.; Waanders, Femke; Slagman, Maartje C. J.; Dokter, Martin M.; Laverman, Gozewijn D.; de Boer, Rudolf A.; Navis, Gerjan

    2013-01-01

    Objective:Sodium restriction potentiates the efficacy of the rennin-angiotensin-aldosterone system (RAAS)-blockade and improves long-term cardiovascular and renal protection, even independent of the better blood pressure control. The mechanisms underlying the potentiation of cardiorenal protection b

  17. 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.

  18. Inducible Knock-Down of the Mineralocorticoid Receptor in Mice Disturbs Regulation of the Renin-Angiotensin-Aldosterone System and Attenuates Heart Failure Induced by Pressure Overload.

    Directory of Open Access Journals (Sweden)

    Elena Montes-Cobos

    Full Text Available Mineralocorticoid receptor (MR inactivation in mice results in early postnatal lethality. Therefore we generated mice in which MR expression can be silenced during adulthood by administration of doxycycline (Dox. Using a lentiviral approach, we obtained two lines of transgenic mice harboring a construct that allows for regulatable MR inactivation by RNAi and concomitant expression of eGFP. MR mRNA levels in heart and kidney of inducible MR knock-down mice were unaltered in the absence of Dox, confirming the tightness of the system. In contrast, two weeks after Dox administration MR expression was significantly diminished in a variety of tissues. In the kidney, this resulted in lower mRNA levels of selected target genes, which was accompanied by strongly increased serum aldosterone and plasma renin levels as well as by elevated sodium excretion. In the healthy heart, gene expression and the amount of collagen were unchanged despite MR levels being significantly reduced. After transverse aortic constriction, however, cardiac hypertrophy and progressive heart failure were attenuated by MR silencing, fibrosis was unaffected and mRNA levels of a subset of genes reduced. Taken together, we believe that this mouse model is a useful tool to investigate the role of the MR in pathophysiological processes.

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

    Science.gov (United States)

    2017-01-01

    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.

  20. Serum sodium levels of heart failure and its influence on plasma renin-angiotensin-aldosterone system and brain natriuretic peptide levels%心力衰竭血钠水平对 RAAS 及 BNP 水平的影响

    Institute of Scientific and Technical Information of China (English)

    王玉东; 任松涛; 蔡青云

    2014-01-01

    Objective To study the correlation between serum sodium levels of heart failure and plasma renin-angiotensin-aldosterone system( PAAS) and brain natriuretic peptide(BNP) levels . Methods 122 122 patients with heart failure were divided into control ( serum sodium concentration<135 mmol/L ,57 cases) and observation group ( serum sodium concentration≥135 mmol/L , 65 cases) according to serum sodium levels . PRA , Ang Ⅱ , ALD and BNP levels of two groups were compared and analyzed , the correlation between serum sodium levels and levels of PRA ,AngⅡ ,ALD and BNP were analyzed by Pearson correlation analysis . Results Levels of PRA , Ang Ⅱ ,ALD and BNP of observation group were higher than that in control group significantly( P < 0 .05 ) .Pearson correlation analysis showed , serum sodium levels was positively correlated with levels of PRA , Ang Ⅱ , ALD and BNP( P <0 .05 ) .Conclusion Low level serum sodium of heart failure promotes the release of PRA , Ang , ALD and BNP , serum sodium levels is positively correlated with levels of PRA , Ang Ⅱ , ALD and BNP .%目的:研究心力衰竭患者血钠水平与血浆肾素-血管紧张素-醛固酮系统(RAAS)及脑钠肽之间(BNP)的相关性。方法选择我院收治的122例心力衰竭患者,根据血钠水平分为对照组(血清钠离子浓度<135 mmol/L ,57例)和观察组(血清钠离子浓度≥135 mmol/L ,65例),对2组患者的肾素(PRA)、血管紧张素(AngⅡ)、醛固酮(ALD)及BNP水平进行比较分析,并对血钠水平与AngⅡ、ALD及BNP水平的相关性采用 Pearson相关分析。结果观察组的PRA、AngⅡ、ALD及BNP水平显著高于对照组,差异具有统计学意义(P <00.5),通过 Pearson相关分析可见,患者的血钠水平与PRA、AngⅡ、ALD及BNP水平均呈负相关( P <00.5)。结论心力衰竭患者血钠水平低时能促进PRA、AngⅡ、ALD及BNP的释放,且血钠水平

  1. Association of Renin-angiotensin-aldosterone System Gene Polymorphism with the Effect of Angiotensin Receptor Blockers%肾素-血管紧张素-醛固酮系统基因多态性与血管紧张素受体阻滞剂降压疗效相关性的研究进展

    Institute of Scientific and Technical Information of China (English)

    贾坚; 门琛

    2012-01-01

    People recognize that the difference of genetic polymorphism results in the individual difference of drug effect, as the development of the human genome project and pharmacogenomics. This paper reviews association of renin-angiotensin-aldosterone system gene polymorphism with the effect of angiotensin receptor blockers which are used commonly in clinic. The paper also analyzes the possible causes of the contradiction of the research results in the past.%随着人类基因组计划的实施以及药物基因组学研究的进展,人们认识到基因多态性的不同导致了药物治疗效果的个体差异.现综述肾素-血管紧张素-醛固酮系统基因多态性与临床上常用的血管紧张素受体阻滞剂降压疗效的相关性,并分析以往研究结果矛盾的可能原因.

  2. The role of renin-angiotensin-aldosterone system in salty taste and sodium intake regulation%肾素-血管紧张素-醛固酮系统在咸味觉功能及摄钠调控中的作用

    Institute of Scientific and Technical Information of China (English)

    吕波; 闫剑群

    2011-01-01

    咸味觉感受功能对摄钠行为的引导和调控至关重要,体钠平衡失调将引起一系列神经内分泌变化以产生钠欲,并伴有咸味觉感受功能的变化.肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system,RAAS)的多个成分在体钠平衡失调对咸味觉功能的调控中扮演重要角色.外周及脑源性血管紧张素II(angiotensin II,ANG II)和醛固酮(aldosterone,ALD)可协同作用于中枢相应敏感神经元,调控动物咸味觉喜好及敏感性,进而调控摄钠行为,并帮助机体维持体钠平衡.

  3. Renin-angiotensin-aldosterone system changes in pediatric severe sepsis treated with continuous blood purification%儿童严重脓毒症连续性血液净化治疗时肾素-血管紧张素-醛固酮系统的变化

    Institute of Scientific and Technical Information of China (English)

    朱艳; 张育才; 肖政辉; 崔云; 戎群芳; 徐梁; 蒋慧

    2015-01-01

    Objective To explore the changes of renin-angiotensin-aldosterone system in pediatric severe sepsis treated with continuous blood purification(CBP).Methods Prospective study,35 cases of critically ill children diagnosed with severe sepsis and admitted to PICU of Shanghai Children's Hospital of Shanghai Jiaotong University from June 2012 to May 2014 served as reseach objective.Based on the monitoring of vital signs,including central venous pressure,arterial blood pressure,mean arterial pressure,patients were treated with conventional therapy,as antibiotics,fluid therapy,and CBP by mode of continuous veno-venous hemodiafiltration or high volume hemofiltration.Plasma levels of rennin activity,angiontensin Ⅱ and aldosterone were measured by radioimmunoassay before and 24 h after CBP.Twenty-five cases of blood samples taken from the children collected from health care for liver function examination were matched as control group.Results Plasmalevelsofrenninactivitywere(2.11 ±1.93) pg/(L·h),(1.27±1.56) μg/(L·h),(0.37 ± 0.22) μg/(L· h) before and 24 h after CBP and control group,respectively.The levels of angiontensin Ⅱ were (426.78 ±332.37) ng/L,(364.40 ± 325.51) ng/L,(41.70 ± 10.81) ng/L,respectively.And the levels of aldosterone were (255.12 ± 218.18) ng/L,(134.92 ± 104.13) ng/L,(106.88 ±43.18) ng/L,respectively.The plasma levels of rennin activity,angiontensin Ⅱ,and aldosterone were higher in sepsis cases than in control group,while decreased obviously after CBP treatment(P <0.01,P <0.05).Eleven cases died and mortality was 31.4% (11/35).After 24 h of CBP,the mean arterial pressure improved in 26 cases with septic shock and dopamine dose reduced(P < 0.01).Conclusion The reaction of renin-angiotensin-aldosterone system is increased significantly in pediatric severe sepsis.CBP can down-regulate the levels of rennin activity,angiotensin Ⅱand aldosterone,but not worsen the circulation function.%目的

  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. 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 no

  6. 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 no

  7. Renin-angiotensin-aldosterone system (RAAS) and its pharmacologic modulation

    OpenAIRE

    Giestas, A.; Palma, I.; Ramos, M. (ed.)

    2010-01-01

    O sistema-renina-angiotensina-aldosterona (SRAA) é um sistema neuroendócrino complexo responsável pela modulação do equilíbrio hidroelectrolítico e regulação da pressão arterial. Através das suas múltiplas interacções contribui para a protecção do tecido endotelial, cardíaco, cerebral e renal. Adicionalmente, regula ainda a resposta do endotélio à inflamação e lesão. A sua activação crónica/desregulação induz hipertensão e perpetuação de uma cascata pró-inflamatória, pró-trombó...

  8. [Renin-angiotensin-aldosterone system in diabetes insipidus].

    Science.gov (United States)

    Kirillov, G; Ankov, V

    1980-01-01

    Plasma renin activity (PR) and plasma aldosterone level (PA) were investigated in 38 patients with central diabetes incipidus under conditions of standard sodium intake and after a three-day reduction of sodium in the diet with an additional furosemide load. Blood was recovered for examination in the morning under complete rest and after a two-hour slow walk. Apparently healthy volunteers (20) served as control. The PR and PA content was determined by the radioimmunological method. Not only the basic, but also the stimulated renin secretion was increased in patients with diabetes incipidus. The basic PA level was significantly diminished; after stimulation its level did not differ from that in healthy persons. At rest and with decreased sodium intake the patients displayed two types of PR activity: in some (n=18) there was no elevation, and in other (n=19) the rise was marked. It is supposed that in diabetes incipidus hyperreninemia was compensatory, directed to water retention in the organism; apparently it participated in the mechanism of hypovolemic thirst. An unusual combination of increased PR with diminished PA level is described for the first time.

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

    African Journals Online (AJOL)

    nephropathy, Azotemia, Proteinuria, Aldosterone, Renin, Blood pressure. Tropical .... creatinine, MAP: mean arterial blood pressure, NS: not significant, U P/Cr: urinary protein/creatinine ratio .... laboratory and clinical monitoring of these.

  10. SARTANS AND ANGIOTENSIN CONVERTING ENZYME INHIBITORS: A DUEL BETWEEN TWO LEADERS OF PHARMACOTHERAPY OF CARDIOVASCULAR DISEASES

    OpenAIRE

    K. A. Gyamdzhyan; M. L. Maksimov

    2015-01-01

    Topical issues of cardiovascular disease pharmacotherapy influencing function of the renin-angiotensin-aldosterone system are discussed. Efficacy and safety of two major cardiovascular drug classes, angiotensin converting enzyme inhibitors and sartans, are compared. Data from evidence base of the both drug classes are presented.

  11. Progress on the association between ACE (I/D) gene polymorphism and renin-angiotensin- aldosterone system and cardiovascular disease%ACE基因插入/缺失多态性与肾素-血管紧张素-醛固酮系统及相关心血管疾病的关系研究进展

    Institute of Scientific and Technical Information of China (English)

    于彦彦; 董天葳; 隋小芳; 彭鹏; 杨军

    2015-01-01

    肾素-血管紧张素-醛固酮系统(RAAS)是人体内重要的体液调节系统。RAAS存在于血管壁、心脏、肾脏和肾上腺等组织中,作用于循环系统,参与对靶器官的调节。在正常情况下,它具有调节水、盐平衡,血管张力和交感神经活性,维持内环境稳定,调节血压以及对心血管系统的正常发育、功能稳态等作用而被认为与心血管疾病的发生、发展及预后有密切联系;因此编码该系统的各个基因就成为许多课题研究的很有吸引力且极具价值的候选基因。RAAS 在健康和疾病中发挥着中心作用,但该系统活性的决定因素尚未完全阐明。血管紧张素转换酶(ACE)是RAAS中的一种关键酶,它主要将血管紧张素Ⅰ(AngⅠ)水解转化成具有强大生物活性的血管紧张素Ⅱ(AngⅡ),同时降解缓激肽使之失活。目前,ACE基因插入/缺失(I/D)多态性与冠心病、心肌病、高血压等心血管疾病的关系已引起人们广泛的注意,研究报道很多,但结果不一。因此探讨ACE基因多态性与RAAS及相关心血管疾病关系的重要性,无论是在阐明疾病的分子生物学发病机制,还是指导临床药物的应用,都会带来前所未有的启发。%Renin-angiotensin-aldosterone system (RAAS) is the most important endocrine mechanism in our body. It works on circulation system and involves in the regulation of target organs. It is thought to be associated with the occurrence, development and prognosis of cardiovascular disease, because it has the effects such as adjusting water and salt balance, participateing vascular tone and sympathetic activity, maintaining environmental stability, regulating blood pressure, effecting the normal development of the cardiovascular system and cardiovascular homeostasis and other local effects. Therefore, each gene encoding RAAS becomes very attractive and valuable candidate genes. RAAS plays a

  12. The effects of direct renin inhibitor, aliskiren, on arterial hypertension, chronic kidney disease and cardiovascular disease: optimal pharmacotherapy.

    Science.gov (United States)

    Morishita, Yoshiyuki; Kusano, Eiji

    2013-03-01

    The renin-angiotensin-aldosterone system (RAAS) plays pivotal roles in the pathogenesis of progression of arterial hypertension, chronic kidney disease (CKD) and cardiovascular disease (CVD). Previous studies suggested that a direct renin inhibitor, aliskiren, may be effective for blood pressure lowering, renoprotection and cardiovascular protection. This review focuses on the effects of aliskiren for arterial hypertension, CKD and CVD.

  13. Effects of short-term addition of NSAID to diuretics and/or RAAS-inhibitors on blood pressure and renal function

    NARCIS (Netherlands)

    Nygard, Peder; Jansman, Frank G. A.; Kruik-Kolloffel, Willemien J.; Barnaart, Alex F. W.; Brouwers, Jacobus R. B. J.

    2012-01-01

    Background The combined post-operative use of diuretics and/or renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of nonsteroidal anti-inflammatory drug (NSAID) associated renal failure because of a drug-drug interaction. Objective The aim of this study was to investigate t

  14. Influential factors of renin-angiotensin-aldosterone system in patients with essential hypertension%原发性高血压病患者肾素-血管紧张素-醛固酮系统活性的影响因素

    Institute of Scientific and Technical Information of China (English)

    符春晖; 严华; 陆永光; 陈湘桂; 黄军章

    2011-01-01

    Objective To study the influential factors of renin-angiotensin-aldosterone system in essential hypertension. Methods One hundred patients with essential hypertension were divided into groups according to blood pressure grades, ages and body mass indexes. The levels of plasma renin activity, angiotensin Ⅱ and aldosterone were measured with radioimmunoassay at erect and decubitus position. Multiple linear regression analysis was performed to evaluate the relationships of age,height, body mass, systolic blood pressure and diastolic blood pressure with plasma renin activity,angiotensin Ⅱ and aldosterone. Results With the severity of the blood pressure, the levels of plasma renin activity decreased, but angiotensin Ⅱ and aldosterone increased, which showed significant differences in three hypertension groups(P<0.05). The levels of plasma renin activity, angiotensin Ⅱ and aldosterone decreased with the aging in three different ages groups(P<0.01), and showed no significant differences in three different body mass index groups(P>0.05). Multiple linear regression analysis showed systolic blood pressure and diastolic blood pressure were the positive independent predictors, and the age was the negative independent predictor for angiotensin Ⅱ and aldosterone.The age, systolic blood pressure and diastolic blood pressure were the negative independent predictors for plasma renin activity. The height, body mass and body mass index were not correlated with plasma renin activity, angiotensin Ⅱ and aldosterone. Conclusion The over-reactivity of reninangiotensin-aldosterone system could be observed in patients with essential hypertension, which is closely correlated with the age and blood pressure.%目的:探讨原发性高血压病患者血浆肾素-血管紧张素Ⅱ-醛固酮水平的影响因素.方法:原发性高血压病男性患者100例分别按高血压级别、年龄及体质量指数(body mass index,BMI)进行分组,采用放射免疫方法测定立位

  15. 不同术后镇痛方法对血浆肾素-血管紧张素Ⅱ-醛固酮系统的影响%Influence of postoperative analgesic method on plasma renin-angiotensin-aldosterone system in patients undergoing hysterectomy

    Institute of Scientific and Technical Information of China (English)

    余微萍; 徐旭仲; 温怀凯; 寿红艳

    2001-01-01

    目的:观察不同术后镇痛方法对子宫切除术患者血浆肾素-血管紧张素-醛固酮(R-A-A)系统的影响。方法: 将36例ASAⅠ~Ⅱ级子宫切除术患者,随机分为持续硬膜外输注镇痛(CEA)组、持续静脉输注镇痛(CIA)组和哌替啶肌注镇痛(MA)组,每组12例。分别于麻醉前(T0)、术毕使用镇痛药前(T1)、术后4小时(T2)和术后第一天晨7时(T3)采静脉血测定血浆肾素、血管紧张素Ⅱ和醛固酮浓度。结果: 与T0比较,肾素水平CEA组、CIA组在T3升高,MA组在T2显著降低(P<0.01);血管紧张素ⅡCEA组在T2、T3和MA组在T3均显著降低(P<0.01);醛固酮CEA组在T3显著降低(P<0.01),MA组在T2升高(P<0.01),而T3时降低(P<0.01)。组间比较,CEA组、MA组在T2和T3时肾素、血管紧张素Ⅱ、在T3时醛固酮浓度显著低于CIA组(P小于0.05或 0.01)。结论:CIA患者R-A-A系统较稳定,CEA患者R-A-A系统被抑制。%Objective:To study the effects of postoperative analgesia on plasma renin-angiotensin-aldosterone(R-A-A)system in patients undergoing hysterectomy.Methods:Thirty-six patients,ASA gradeⅠ~Ⅱ,scheduled for elective hysterectomy ,were randomly divided into continuous epidural analgesia(CEA),continuous introvenous analgesia(CIA) and traditional meperidine intramuscular analgesia(MA) groups. Plasma renin,angiotensin and aldosterone concentrations were measured before anesthesia(T0),operation over and before analgesia(T1),4h after operation(T2),and 7o'clock of next day after surgery.Results:Compared with T0 ,renin levels at T3 were significantly higher in CEA and CIA groups (P<0.05),but in MA group, it was markedly low at T2 (P<0.01),Angiotensin concentrations at T2 and T3 were significantly low in CEA group(P<0.01),and significantly low at T3 in MA group(P<0.01),aldosterone constrations increased significantly in three groups at T1(P<0.05 or 0.01),but decreased markedly at T3 in CEA group

  16. 5/6肾切除大鼠肾组织肾素-血管紧张素-醛固酮系统的昼夜节律%Rhythmic Renin-Angiotensin-Aldosterone System Expression in Circulating and Kidney in 5/6 Nephrectomy Rats

    Institute of Scientific and Technical Information of China (English)

    梁鸿卿; 高秀伦; 朱双益; 黄小妹; 张介眉; 丁国华; 梁伟; 马威; 何达; 熊飞; 程力

    2011-01-01

    Objective: To explore diurnal variation of renin - angiotensin - aldosterone system( RAAS ) in plasma and kidney of chronic kidney disease( CKD ) . Methods: A rat model of CKD was set up by 5/6 subtotal nephrectomy( STNx ) . Wistar rats were randomly divided into sham STNx group( Group A ), STNx group( Group B ), Rats were housed in a temperature - controled room ( 22 ± 2 )℃ and synchronized 12 weeks to the light( L )dark( D )cycle 12:12 with light on from 7:00 a. M. ( Zeitgeber time ZT 0 ). Urinary protein excretion in 24 h and blood urea nitrogen and serum creatinine were examined on week 11 and week 12 respectively. The expression of renin activity( RA ) , angiotensin Ⅱ ( Ang Ⅱ )and aldosterone( Ald ) in plasma and kidney tissue were examined by ra-dioimmunoassay( RIA ) on week 12. Results: Urinary protein excretion in 24 h and blood urea nitrogen and serum creatinine were elevated significantly in STNx rats( P <0. 001 ). The expression of RA , Ang Ⅱ and Ald in kidney tissue showed different circadian rhythm to that of in plasma. The peak and trough time of kidney renin activity( KRA ) in group A and group B were opposite to that of plasma rein activity( PRA ), the peak time of Ang Ⅱ moved from ZT20( GroupA ) or ZT16( Group B ) in plasma to ZT4 in kidney . The rhythms of the expression of RAAS components in group B were also different to that of in group A. Conclusion: The expression rhythm of RAAS components in kidney were quite different to that in plasma, and it also changed in CKD rats.%目的:研究慢性肾衰竭大鼠循环及肾局部肾素-血管紧张素-醛固酮(RAAS)的近日节律.方法:60只Wistar大鼠建立5/6肾衰竭大鼠模型,随机分为两组:肾衰组(A组,30只),假手术组(B组,30只).大鼠在恒温(22±2)℃,12:12 h明(L):暗(D)交替的环境中饲养12周.早上7:00开灯,记为ZT0时,依次类推,晚上19:00时关灯,记为ZT12时.在11周时留尿测24 h尿蛋白定量.12周时分别留取血及肾标本.放免法

  17. Blockade of the renin-angiotensin system

    OpenAIRE

    Cheung, BMY.

    2002-01-01

    The renin-angiotensin-aldosterone system plays a key role in the regulation of fluid and electrolyte balance. Angiotensin-converting enzyme inhibitors inhibit angiotensin-converting enzyme and have been shown to be effective in many cardiovascular diseases. They should be considered for the treatment of hypertension in patients with heart failure, previous myocardial infarction, diabetes, or proteinuria. There are a number of side-effects associated with angiotensin-converting enzyme inhibito...

  18. 体位性心动过速综合征患儿24小时尿钠变化与肾素-血管紧张素-醛固酮系统调节的关系%Relationship between 24-hour urinary sodium and renin-angiotensin-aldosterone system in children with postural tachycardia syndrome

    Institute of Scientific and Technical Information of China (English)

    李佳蔚; 廖莹; 杜军保; 张清友

    2015-01-01

    Objective To analyze the relationship between 24 hours urinary sodium and reninangiotensin-aldosterone system (RAAS) in children with postural tachycardia syndrome (POTS) and to explore low blood volume related pathogenesis of POTS.Methods A total of 39 POTS children who were at the clinic or admitted to the Department of Pediatrics,Peking University First Hospital from June 2012 to February 2013 and 21 healthy children (control group) were enrolled,level of RAAS in plasma,24-hour urinary sodium and plasma sodium were detected,respectively.Baseline data,levels of RAAS and hemodynamic parameters were compared between POTS and control group,as well as groups with different 24-hour urinary sodium levels of POTS.Results The angiotensin Ⅱ levels of POTS children were significantly higher than that of control group ((105 ± 50) vs (84 ± 28) ng/L,P =0.041),while no statistical significance was found in plasma renin and aldosterone (P > 0.05).Pearson correlation analysis showed that 24-hour urinary sodium and angiotensin Ⅱ in children with POTS was negatively correlated (r =-0.536,P <0.001).Angiotensin Ⅱ,symptom score,upright heart rate and changes of heart rate were significantly higher in urinary sodium < 124 mmol/24 h group than that in urinary sodium ≥ 124 mmol/24 h group (P < 0.05).Conclusion The regulating function disorder of RAAS may involve in the pathogenesis of POTS and cause sustained low blood volume in patients with POTS.%目的 分析体位性心动过速综合征(POTS)患儿24 h尿钠与肾素-血管紧张素-醛固酮系统(RAAS)之间的关系,探讨POTS与血容量降低相关的发病机制.方法 收集2012年6月至2013年2月就诊于北京大学第一医院儿科诊断为POTS的39例患儿(POTS组)和21名健康体检的对照组儿童资料.所有研究对象均检测血浆RAAS、血钠水平及24 h尿钠水平.比较POTS组与对照组,以及不同24h尿钠水平组POTS患儿的基本资料、RAAS水平

  19. 肾血管性高血压和肾上腺腺瘤患者肾素-血管紧张素-醛固酮含量分析%Clinical assay of renin-angiotensin-aldosterone system,endothelin and nitric oxide in renovacular hypentension and adrenocorticoadenoma

    Institute of Scientific and Technical Information of China (English)

    马伦; 吴照芝

    2008-01-01

    Objective To investigate the roles of renin-angiotens in system(RAS)and aldosterone(ALD),endothelin(ET),nitricoxide(NO)in patients with renal hypertension(40 cases)and adrenocorticoadenomas(35 cases),35 normal subjects were included in the study as controls.Methods Radioimmunoassay(RIA)was used to de termine the plasma concentrations of the renin,angiorensin Ⅱ(AⅡ),aldosterone,ET in the abovecases.Enzymicas say was adopted to examine the plasma concentration of the nitricoxidesynthase(NOS).Results TIhe plasma concentrations of renin,angiotennsin Ⅱ,aldosterone,endothefin in the patients with renal hypertension were significantly higher than those in the control group(P<0.01)except with the concentration of NOS,which were lower than that in controls(P<0.05);the plasma concentrations of the ALD,ET,in the patients with adrenocorti-caladenoma were higher that those in controls(P<0.01)but renin and A Ⅱ were lower(P<0.05).Conclusion Determination of the plasma renin,angiotensionⅡ,aldosterone and NO might be able diagnose renal hypertension and adrenocorti coadenoma earlier.%目的 探讨肾素-血管紧张素-醛固酮系统、内皮素、一氧化氮在肾血管性高血压患者、肾上腺腺瘤患者中的作用和意义.方法 采用放射免疫分析的方法测量肾血管性高血压组(40例)、肾上腺腺瘤组(35例)和健康对照组(35例)血清肾素、血管紧张素Ⅱ、醛固酮、内皮素含量,用酶免疫法测定上述人群一氧化氮合酶(NOS)的含量来表示NO的量.结果 肾血管性高血压患者肾素、血管紧张素、醛固酮、内皮素含量高于健康对照组(P<0.01),NOS含量低于健康对照组(P<0.05);肾上腺腺瘤组醛固酮和内皮素含量高于健康对照组(P<0.01),肾素、血管紧张素低于健康对照组(P<0.05).结论 肾索、血管紧张素、醛固酮、内皮素和NO的检测可为临床早期诊断肾上腺腺瘤、肾血管性高血压提供依据.

  20. 经皮肾脏交感神经射频消融术对顽固性高血压患者肾素血管紧张系统的影响%The effect of catheter based renal symthetic denervation on renin-angiotensin-aldosterone system in patients with resistant hypertension

    Institute of Scientific and Technical Information of China (English)

    王丽; 卢成志; 张欣; 罗迪; 赵斌; 于翔; 夏大胜; 陈欣; 赵向东

    2013-01-01

    Objective to explore the effect of catheter based renal symthetic denervation on reninangiotensin-aldosterone system(RAAS)and blood pressure reduction in patients with resistant hypertension.and assess the validity and security of the treatment.Methods Ten patients with resistant hypertension from June 2011 to December 2011 were retrospectively reviewed,and then all of 10 patients screened for eligibility were allocated to renal denervation.Primary endpoints were changes of office blood pressure at 1week,1,3 and 6 months after procedure.We assessed the effectiveness of renal sympathetic denervation with heart rate (HR),renin activity (PRA),angiotensin Ⅱ (Ang Ⅱ),aldosterone(Ald),and creatinine(Cr)before and 2 weeks after procedure.Results Office blood pressure after catheter-based renal denervation decreased by 22.8/9.1 mm Hg(1 mm Hg =0.133 kPa),34.8/14.7 mm Hg,42.6/20.7 mm Hg,43.2/21.6 mm Hg,at 1 week,1,3 and 6 months,respectively(P < 0.001).Meanwhile,the level of PRA,Ang Ⅱ,Alddecreased by (1.11±0.89)ng· ml-1 · h-1(P=0.003),(17.06±13.82) ng/L (P=0.004),(404.5 ±285.8) ng/L (P =0.002),respectively; and heart rate decreased by 5.1 bpm (P =0.002).However,the Cr level and eGFR did not change significantly (P > 0.05).Conclusion Catheter-based renal sympathetic denervation can reduce the level of renin activity,angiotensin Ⅱ and aldosterone,and causes substantial and sustained blood-pressure reduction.%目的 观察经皮肾交感神经射频消融对顽固性高血压患者肾素-血管紧张素-醛固酮系统(RAAS)的影响及降压效果,并对肾交感神经射频消融的安全性及有效性进行分析.方法 连续入选白2011年6月至12月在我科住院治疗的顽固性高血压病患者10例,行经皮肾交感神经射频消融术,观察术前及术后1周、1、3和6个月的血压变化及肾素、血管紧张素Ⅱ、醛固酮、肌酐、尿常规、心率等指标,评价手术的有效性与安全性并探讨其机制.结果 经

  1. Are "functionally related polymorphisms" of renin-angiotensin-aldosterone system gene polymorphisms associated with hypertension?

    NARCIS (Netherlands)

    Hahntow, I.N.; Mairuhu, G.; Valkengoed, I.G.M.; Koopmans, R.P.; Michel, M.C.

    2010-01-01

    ABSTRACT: BACKGROUND: Genotype-phenotype association studies are typically based upon polymorphisms or haplotypes comprised of multiple polymorphisms within a single gene. It has been proposed that combinations of polymorphisms in distinct genes, which functionally impact the same phenotype, may hav

  2. Effects of cilazapril on endothelial cell function and fibrinolysis system in atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    HAN Wei; LI Wei-min; XIE Bao-dong; LI Yue; ZHAO Ji-yi; HUANG Yong-lin

    2005-01-01

    @@ Recently, it has been found that atrial fibrillation (AF) is associated with renin angiotensin aldosterone system (RAAS) activation and that angiotensin converting enzyme inhibition (ACEI) reduces incidence of AF in hypertensive patients.

  3. Renal graft failure after addition of an angiotensin II receptor antagonist to an angiotensin-converting enzyme inhibitor

    DEFF Research Database (Denmark)

    Kamper, Anne-Lise; Nielsen, Arne Høj; Baekgaard, Niels

    2002-01-01

    Combined treatment with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor blocker (ARB) has been suggested in order to achieve a more complete blockade of the renin-angiotensin-aldosterone system in cardiovascular and renal disease. The present report...... describes a case of acute renal graft dysfunction following the addition of an ARB to existing ACE inhibition. This unmasked an unknown iliac artery stenosis. The case indicates a possible important role of Ang II generated by non-ACE pathways in this situation....

  4. Aliskiren – an orally active renin inhibitor. Review of pharmacology, pharmacodynamics, kinetics, and clinical potential in the treatment of hypertension

    Directory of Open Access Journals (Sweden)

    Kristina Allikmets

    2008-01-01

    Full Text Available Kristina AllikmetsDepartment of Drug Development and Medical Affairs, Nycomed Group, Roskilde, DenmarkAbstract: The importance of renin-angiotensin-aldosterone system (RAAS in diseases such as hypertension, congestive heart failure and chronic renal failure has long ago been recognized. It has also been established that inhibition of RAAS, using inhibitors of the angiotensin-converting enzyme (ACE or angiotensin II receptor blockers (ARB, is an effective way to intervene with the pathogenesis of these disorders. Renin inhibitors block the RAAS at the highest level, at its origin, and might thus offer a new exciting approach for pharmacotherapy of arterial hypertension. Aliskiren is the first in a new class of orally active, non-peptide, low molecular weight renin inhibitors, and so far the only renin inhibitor that has progressed to phase III clinical trials. This review summarizes the available data on the pharmacokinetic and pharmacodynamic properties of aliskiren and its clinical development for treatment of arterial hypertension.Keywords: aliskiren, hypertension, renin-angiotensin-aldosterone system, renin inhibition, essential hypertension

  5. Systemic effects of angiotensin III in conscious dogs during acute double blockade of the renin-angiotensin-aldosterone-system

    DEFF Research Database (Denmark)

    Gammelgaard, Iben; Wamberg, Søren; Bie, Peter

    2006-01-01

    AIMS: The study was designed to determine (i) whether the effects of angiotensin III (AngIII) are similar to those of angiotensin II (AngII) at identical plasma concentrations and (ii) whether AngIII operates solely through AT1- receptors. METHODS: Angiotensin II (3 pmol kg(-1) min(-1)-3.1 ng kg(...

  6. 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 ev

  7. 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

  8. Renin-angiotensin-aldosterone system and electrolyte metabolism in rat blood after flight aboard Cosmos-1129 biosatellite

    Energy Technology Data Exchange (ETDEWEB)

    Kvetnansky, R.; Tigranyan, R.A.; Jindra, A.; Viting, T.A.

    1982-08-01

    Blood plasma aldosterone concentration and renin activity were studied in rats flow in space on the Cosmos 1129 satellite using radioimmunoassay techniques. Immediately after the flight, the animals presented significant decreases in plasma renin activity, as compared to rats in the vivarium control and animals in the synchronous experiment. R. J.

  9. The role of renin-angiotensin-aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    I.C.R.M. Kolder (Iris); M. Michels (Michelle); I. Christiaans (Imke); F.J. ten Cate (Folkert); D.F. Majoor-Krakauer (Danielle); A.H.J. Danser (Jan); R.H. Lekanne Deprez; M.W.T. Tanck (Michael); A.A.M. Wilde (Arthur); C.R. Bezzina (Connie); D. Dooijes (Dennis)

    2012-01-01

    textabstractThe phenotypic variability of hypertrophic cardiomyopathy (HCM) in patients with identical pathogenic mutations suggests additional modifiers. In view of the regulatory role in cardiac function, blood pressure, and electrolyte homeostasis, polymorphisms in the

  10. Applications of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the treatment of chronic heart failure%血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂在慢性心力衰竭治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    居海宁; 卞金陵

    2011-01-01

    Heart failure is the ultimate cause of death in a variety of heart diseases. It has been discovered that the main strategy of slowing the progress of heart failure diseases is blocking the renin angiotensin aldosterone system (RAAS). Angiotensin converting enzyme inhibitors(ACEI) and angiotensin receptor blockers( ARB) are the most commonly used RAAS-blocking drugs. In this paper,the assessment of chronic heart failure and the applications of ACEI and ARB in the treatment of chronic heart failure are reviewed.%心力衰竭是多种心脏病的最终死亡原因,阻断肾素-血管紧张素-醛固酮系统(renin angiotensin aldosterone system,RAAS)是减慢心力衰竭病变进展的主要策略.血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitors,ACEI)和血管紧张素受体拮抗剂(angiotensin receptor blockers,ARB)是目前最常用的阻断RAAS的药物.本文对慢性心力衰竭评估,以及ACEI和ARB在慢性心力衰竭治疗中的应用进行综述.

  11. Aliskiren, the first direct renin inhibitor for treatment of hypertension: The path of its development

    Directory of Open Access Journals (Sweden)

    M Jadhav

    2012-01-01

    Full Text Available Standard treatments available today for treating hypertension is diuretics, β-blockers, angiotensin converting enzyme inhibitors (ACEs, angiotensin receptor blockers (ARBs, calcium channel blockers, a-blockers, vasodilators, and centrally acting drugs. It is difficult to achieve the optimized renin angiotensin aldosterone system suppression with currently available antihypertensive agents, because ACE inhibitors, ARBs, and diuretics all activate the compensatory feedback mechanism that increases renin release and increase plasma renin activity. The first orally active direct renin inhibitors (DRIs were developed in 1980s, including enalkiren, remikiren, and zankiren. However, poor absorption from the gastrointestinal tract, less bioavailability (<2%, short half life, and low potency hindered the development of these compounds. Aliskiren is the first DRI for the treatment of hypertension. Aliskiren is designed through a combination of molecular modeling techniques and crystal structure elucidation. Aliskiren effectively reduces the blood pressure as a mono therapy as well in combination therapy.

  12. [Role of matrix metalloproteinases and tissue inhibitors of metalloproteinases in hypertension. Pathogenesis of hypertension and obesity].

    Science.gov (United States)

    Trojanek, Joanna B

    2015-01-01

    Hypertension (HT), obesity and related metabolic disorders are increasing cause diseases with risk of premature death in western societies. Both hypertension and obesity are characterized by similar disorders such as chronic low systemic inflammation, changes in the vessel wall, abdominal obesity, insulin-resistance or dyslipidemia. Chronic, untreated HT leads to adverse changes in internal organs like kidney damage, arterial remodeling and hypertrophy of the left ventricle. The important role metalloproteinases and their inhibitors (TIMPs) in the pathophysiology of hypertension is associated with the degradation of vascular wall components, especially collagen and elastin. The activated RAAS system (renin-angiotensin-aldosterone) is displaying direct impact in the pathogenesis and progress of hypertension. Angiotensin II affects the expression and activation of many growth factors, cytokines and MMPs. The fat tissue of obese people is in the state of low intensity chronic inflammation and undergoes continual process of remodeling. Obesity is one of the direct cause of hypertension.

  13. Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and RAAS inhibitors

    Directory of Open Access Journals (Sweden)

    Alberto F Rubio-Guerra

    2009-11-01

    Full Text Available Alberto F Rubio-Guerra1, David Castro-Serna2, Cesar I Elizalde Barrera2, Luz M Ramos-Brizuela21Metabolic and Research Clinic, 2Internal Medicine Department, Hospital General de Ticomán SS DF, MéxicoAbstract: Recent guidelines for the management of hypertension recommend target blood pressures <140/90 mmHg in hypertensive patients, or <130/80 mmHg in subjects with diabetes, chronic kidney disease, or coronary artery disease. Despite the availability and efficacy of antihypertensive drugs, most hypertensive patients do not reach the recommended treatment targets with monotherapy, making combination therapy necessary to achieve the therapeutic goal. Combination therapy with 2 or more agents is the most effective method for achieving strict blood pressure goals. Fixed-dose combination simplifies treatment, reduces costs, and improves adherence. There are many drug choices for combination therapy, but few data are available about the efficacy and safety of some specific combinations. Combination therapy of calcium antagonists and inhibitors of the renin-angiotensin-aldosterone system (RAAS are efficacious and safe, and have been considered rational by both the JNC 7 and the 2007 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. The aim of this review is to discuss some relevant issues about the use of combinations with calcium channel blockers and RAAS inhibitors in the treatment of hypertension.Keywords: hypertension, calcium channel blockers, renin-angiotensin-aldosterone system inhibitors, fixed-dose combination, adherence

  14. 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...

  15. Improvement of Sodium Status to Optimize the Efficacy of Renin-Angiotensin System Blockade

    NARCIS (Netherlands)

    Laverman, Gozewijn D.; Navis, Gerjan

    2011-01-01

    Blockade of the renin-angiotensin-aldosterone system (RAAS) offers superior renoprotection in the treatment of patients with hypertension, but the efficacy of RAAS inhibition strongly depends on sodium status, presumably in relation to extracellular volume status. Because assessing volume status by

  16. Improvement of Sodium Status to Optimize the Efficacy of Renin-Angiotensin System Blockade

    NARCIS (Netherlands)

    Laverman, Gozewijn D.; Navis, Gerjan

    2011-01-01

    Blockade of the renin-angiotensin-aldosterone system (RAAS) offers superior renoprotection in the treatment of patients with hypertension, but the efficacy of RAAS inhibition strongly depends on sodium status, presumably in relation to extracellular volume status. Because assessing volume status by

  17. The influence of the ACE (I/D) polymorphism on systemic and renal vascular responses to angiotensins in normotensive, normoalbuminuric Type 1 diabetes mellitus

    NARCIS (Netherlands)

    Luik, PT; Hoogenberg, K; Kerstens, MN; Beusekamp, BJ; de Jong, PE; Dullaart, RPF; Navis, GJ

    Aim/hypothesis. The renin-angiotensin-aldosterone system is important in diabetic nephropathy, with the angiotensin-converting-enzyme DD-genotype being a renal risk factor. The D-allele is associated with higher ACE concentrations, but functional consequences in diabetes mellitus are not known. To

  18. 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.

  19. 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

    AND DISSEMINATION: The study will be conducted under International Conference on Harmonisation - Good clinical practice (ICH-GCP) requirements, ethical principles of Declaration of Helsinki and national laws. This first new biomarker-directed intervention trial aiming at primary prevention of diabetic nephropathy...

  20. 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

    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...

  1. Cushing's disease and hypertension: In vivo and in vitro study of the role of the renin-Angiotensin-Aldosterone system and effects of medical therapy

    NARCIS (Netherlands)

    R. van der Pas (Rob); J.H.M. Esch, van (Joep); C. de Bruin (Christiaan); A.H.J. Danser (Jan); A.M. Pereira (Alberto); P.M. Zelissen (Pierre M.); R.T. Netea-Maier (Romana ); D. Sprij-Mooij (Diana); I.M. van den Berg-Garrelds (I.); R.H.N. van Schaik (Ron); S.W.J. Lamberts (Steven); A.H. van den Meiracker (Anton); L.J. Hofland (Leo); R.A. Feelders (Richard)

    2014-01-01

    textabstractAbstract Objective/methods: Cushing's disease (CD) is often accompanied by hypertension. CD can be treated surgically and, given the expression of somatostatin subtype 5 and dopamine 2 receptors by corticotroph pituitary adenomas, pharmacologically. Indeed, we recently observed that step

  2. Cushing's disease and hypertension: in vivo and in vitro study of the role of the renin-angiotensin-aldosterone system and effects of medical therapy

    NARCIS (Netherlands)

    Pas, R. van der; Esch, J.H. van; Bruin, C. de; Danser, A.H.; Pereira, A.M.; Zelissen, P.M.; Netea-Maier, R.; Sprij-Mooij, D.M.; Berg-Garrelds, I.M. van den; Schaik, R.H. van; Lamberts, S.W.J.; Meiracker, A.H. van den; Hofland, L.J.; Feelders, R.A.

    2014-01-01

    OBJECTIVE/METHODS: Cushing's disease (CD) is often accompanied by hypertension. CD can be treated surgically and, given the expression of somatostatin subtype 5 and dopamine 2 receptors by corticotroph pituitary adenomas, pharmacologically. Indeed, we recently observed that stepwise medical combinat

  3. Gene-Gene Interactions in Renin-Angiotensin-Aldosterone System Contributes to End-Stage Renal Disease Susceptibility in a Han Chinese Population

    Directory of Open Access Journals (Sweden)

    Sui-Lung Su

    2014-01-01

    Full Text Available Objective. In this study, we investigated whether RAAS gene single nucleotide polymorphisms (SNPs and their interactions were associated with end-stage renal stage (ESRD. Methodology and Results. This was a case-control study for 647 ESRD cases and 644 controls. AGT (M235T (rs699 and T174M (rs4762, AGTR1 (A1166C (rs5186 and C573T (rs5182, ACE (I/D (rs1799752 and G2350A (rs4343, and CYP11B2 C-344T (rs1799998 were genotyped and compared between cases and controls to identify SNPs associated with ESRD susceptibility. Multifactor dimensionality reduction (MDR was used to identify gene-gene interactions. Several RAAS genes were associated with ESRD: AGT M235T, ACE I/D, ACE G2350A, and CYP11B2 C-344T. By MDR analysis, a three-locus model (ACE ID/ACE G2350A/CYP11B2 C-344T of gene-gene interaction was the best for predicting ESRD risk, and its maximum testing accuracy was 56.08% and maximum cross-validation consistency was 9/10. ESRD risk was higher with the simultaneous occurrence of ACE I/D DD-ACE G2350A AA. AGT, ACE, and CYP11B2 gene polymorphisms are associated with ESRD. Conclusions. The gene-gene interaction effects of ACE I/D, ACE G2350A, and CYP11B2 C-344T polymorphisms are more important than individual factors for ESRD development among Han Chinese.

  4. 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

    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...... groups, the low-salt diet caused a significantly greater rise in PGE(2) excretion. Furthermore, mRNA expression for COX-2 and PGE(2) synthetic activity was significantly greater in EP4(-/-) than in EP4(+/+) mice. We conclude that low dietary salt intake induces expression of COX-2 followed by enhanced...

  5. 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.

  6. Rationale and Trial Design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes : The Occurrence of Renal Events (BEACON)

    NARCIS (Netherlands)

    de Zeeuw, Dick; Akizawa, Tadao; Agarwal, Rajiv; Audhya, Paul; Bakrise, George L.; Chin, Melanie; Krauth, Melissa; Heerspink, Hiddo J. Lambers; Meyer, Colin J.; McMurray, John J.; Parving, Hans-Henrik; Pergola, Pablo E.; Remuzzi, Giuseppe; Toto, Robert D.; Vaziri, Nosratola D.; Wanner, Christoph; Warnock, David G.; Wittes, Janet; Chertow, Glenn M.

    2013-01-01

    Background: Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a

  7. Rationale and trial design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes

    DEFF Research Database (Denmark)

    de Zeeuw, Dick; Akizawa, Tadao; Agarwal, Rajiv

    2013-01-01

    Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic...

  8. 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.......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....

  9. Aldosterone synthase inhibitors in hypertension: current status and future possibilities

    OpenAIRE

    Milan Hargovan; Albert Ferro

    2014-01-01

    The renin-angiotensin aldosterone system is a critical mechanism for controlling blood pressure, and exerts most of its physiological effects through the action of angiotensin II. In addition to increasing blood pressure by increasing vascular resistance, angiotensin II also stimulates aldosterone secretion from the adrenal gland. Aldosterone acts to cause an increase in sodium and water reabsorption, thus elevating blood pressure. Although treatment with angiotensin converting enzyme inhibit...

  10. 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.

  11. Aldosterone synthase inhibitors in hypertension: current status and future possibilities

    Directory of Open Access Journals (Sweden)

    Milan Hargovan

    2014-02-01

    Full Text Available The renin-angiotensin aldosterone system is a critical mechanism for controlling blood pressure, and exerts most of its physiological effects through the action of angiotensin II. In addition to increasing blood pressure by increasing vascular resistance, angiotensin II also stimulates aldosterone secretion from the adrenal gland. Aldosterone acts to cause an increase in sodium and water reabsorption, thus elevating blood pressure. Although treatment with angiotensin converting enzyme inhibitors initially lowers circulating aldosterone, with chronic treatment aldosterone levels increase back to baseline, a phenomenon termed aldosterone escape; aldosterone blockade may therefore give added value in the treatment of hypertension. The first mineralocorticoid receptor antagonist developed was spironolactone, but its use has been severely hampered by adverse (notably oestrogenic effects. The more recently developed mineralocorticoid receptor antagonist eplerenone exhibits a better adverse effect profile, although it is not devoid of effects similar to spironolactone. In addition, aldosterone activates non-genomic receptors that are not inhibited by either eplerenone or spironolactone. It is believed that deleterious organ remodelling is mediated by aldosterone via such non-genomic pathways. A new class of drugs, the aldosterone synthase inhibitors, is currently under development. These may offer a novel therapeutic approach for both lowering blood pressure and preventing the non-genomic effects of aldosterone. Here, we will review the cardiovascular effects of aldosterone and review the drugs available that target this hormone, with a particular focus on the aldosterone synthase inhibitors.

  12. Aldosterone synthase inhibitors in hypertension: current status and future possibilities.

    Science.gov (United States)

    Hargovan, Milan; Ferro, Albert

    2014-01-01

    The renin-angiotensin aldosterone system is a critical mechanism for controlling blood pressure, and exerts most of its physiological effects through the action of angiotensin II. In addition to increasing blood pressure by increasing vascular resistance, angiotensin II also stimulates aldosterone secretion from the adrenal gland. Aldosterone acts to cause an increase in sodium and water reabsorption, thus elevating blood pressure. Although treatment with angiotensin converting enzyme inhibitors initially lowers circulating aldosterone, with chronic treatment aldosterone levels increase back to baseline, a phenomenon termed aldosterone escape; aldosterone blockade may therefore give added value in the treatment of hypertension. The first mineralocorticoid receptor antagonist developed was spironolactone, but its use has been severely hampered by adverse (notably oestrogenic) effects. The more recently developed mineralocorticoid receptor antagonist eplerenone exhibits a better adverse effect profile, although it is not devoid of effects similar to spironolactone. In addition, aldosterone activates non-genomic receptors that are not inhibited by either eplerenone or spironolactone. It is believed that deleterious organ remodelling is mediated by aldosterone via such non-genomic pathways. A new class of drugs, the aldosterone synthase inhibitors, is currently under development. These may offer a novel therapeutic approach for both lowering blood pressure and preventing the non-genomic effects of aldosterone. Here, we will review the cardiovascular effects of aldosterone and review the drugs available that target this hormone, with a particular focus on the aldosterone synthase inhibitors.

  13. Discovery of Potential Inhibitors of Aldosterone Synthase from Chinese Herbs Using Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation Studies

    Science.gov (United States)

    Lu, Fang; Qiao, Liansheng; Chen, Xi; Li, Gongyu

    2016-01-01

    Aldosterone synthase (CYP11B2) is a key enzyme for the biosynthesis of aldosterone, which plays a significant role for the regulation of blood pressure. Excess aldosterone can cause the dysregulation of the renin-angiotensin-aldosterone system (RAAS) and lead to hypertension. Therefore, research and development of CYP11B2 inhibitor are regarded as a novel approach for the treatment of hypertension. In this study, the pharmacophore models of CYP11B2 inhibitors were generated and the optimal model was used to identify potential CYP11B2 inhibitors from the Traditional Chinese Medicine Database (TCMD, Version 2009). The hits were further refined by molecular docking and the interactions between compounds and CYP11B2 were analyzed. Compounds with high Fitvalue, high docking score, and expected interactions with key residues were selected as potential CYP11B2 inhibitors. Two most promising compounds, ethyl caffeate and labiatenic acid, with high Fitvalue and docking score were reserved for molecular dynamics (MD) study. All of them have stability of ligand binding which suggested that they might perform the inhibitory effect on CYP11B2. This study provided candidates for novel drug-like CYP11B2 inhibitors by molecular simulation methods for the hypertension treatment. PMID:27781210

  14. Discovery of Potential Inhibitors of Aldosterone Synthase from Chinese Herbs Using Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation Studies

    Directory of Open Access Journals (Sweden)

    Ganggang Luo

    2016-01-01

    Full Text Available Aldosterone synthase (CYP11B2 is a key enzyme for the biosynthesis of aldosterone, which plays a significant role for the regulation of blood pressure. Excess aldosterone can cause the dysregulation of the renin-angiotensin-aldosterone system (RAAS and lead to hypertension. Therefore, research and development of CYP11B2 inhibitor are regarded as a novel approach for the treatment of hypertension. In this study, the pharmacophore models of CYP11B2 inhibitors were generated and the optimal model was used to identify potential CYP11B2 inhibitors from the Traditional Chinese Medicine Database (TCMD, Version 2009. The hits were further refined by molecular docking and the interactions between compounds and CYP11B2 were analyzed. Compounds with high Fitvalue, high docking score, and expected interactions with key residues were selected as potential CYP11B2 inhibitors. Two most promising compounds, ethyl caffeate and labiatenic acid, with high Fitvalue and docking score were reserved for molecular dynamics (MD study. All of them have stability of ligand binding which suggested that they might perform the inhibitory effect on CYP11B2. This study provided candidates for novel drug-like CYP11B2 inhibitors by molecular simulation methods for the hypertension treatment.

  15. Angiotensin receptor-neprilysin inhibitors: clinical potential in heart failure and beyond

    Directory of Open Access Journals (Sweden)

    Singh JSS

    2015-06-01

    Full Text Available Jagdeep SS Singh, Chim C Lang Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK Abstract: Heart failure remains a major concern across the globe as life expectancies and delivery of health care continue to improve. There has been a dearth of new developments in heart failure therapies in the last decade until last year, with the release of the results from the PARADIGM-HF Trial heralding the arrival of a promising new class of drug, ie, the angiotensin receptor-neprilysin inhibitor. In this review, we discuss the evolution of our incremental understanding of the neurohormonal mechanisms involved in the pathophysiology of heart failure, which has led to our success in modulating its various pathways. We start by examining the renin-angiotensin-aldosterone system, followed by the challenges of modulating the natriuretic peptide system. We then delve deeper into the pharmacology and mechanisms by which angiotensin receptor-neprilysin inhibitors achieve their significant cardiovascular benefits. Finally, we also consider the potential application of this new class of drug in other areas, such as heart failure with preserved ejection fraction, hypertension, patients with renal impairment, and following myocardial infarction. Keywords: heart failure, angiotensin receptor-neprilysin inhibitor, heart failure with preserved ejection fraction, nesiritide, candoxatril, omapatrilat, hypertension, renal impairment, myocardial infarction

  16. ADMET, Docking studies & binding energy calculations of some Novel ACE - inhibitors for the treatment of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Gade Deepak Reddy

    2012-09-01

    Full Text Available Diabetic Nephropathy (DN is one of the major complications of diabetes mellitus, representing the leading of cause of chronic renal disease and a major cause of morbidity and mortality in both type 1 and type 2 diabetic patients. The Renin-Angiotensin-Aldosterone System (RAAS has been implicated in the pathophysiology of DN, and suggests a therapeutic target for blocking this system. Therefore, inhibition of RAAS plays a crucial role in the treatment of DN and therapeutic intervention mostly involves administration of angiotensin converting enzyme (ACE inhibitors and angiotensin AT1 receptor blockers. In this current study, we have used computational methods to design 37 novel ACE-inhibitors and evaluated them for the interaction with the enzyme ACE through insilico analysis. The obtained results were compared with the standard drug enalapril to find out the potential inhibitors. Here we report that ligand 4 exhibited strongest inhibitory activity among all. All the analogs are also screened for their ADME & Toxicity profiles using insilico tools and ligand 9 is having better binding affinity next to ligand 4, and also having better ADMET profile when compared to that of ligand 4. Post docking calculations were also performed for the docked complexes in order to identify the individual ligand binding energies by employing Multi-Ligand Bimolecular Association with Energetics (Embrace

  17. Effects of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Contrast-Induced Nephropathy

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    Letian Zhou

    2014-03-01

    Full Text Available Contrast-induced nephropathy (CIN is considered the third leading cause of iatrogenic acute kidney injury in high-risk patients undergoing radiographic procedures. The main mechanism leading to CIN is medullary hypoxia due to decreased renal blood flow, secondary to renal artery vasoconstriction and direct tubular toxicity by contrast medium. Furthermore, experimental data suggests that an activated renin-angiotensin-aldosterone system (RAAS plays a role in the pathophysiology of CIN. However, the role of RAAS blockers, including angiotensin-converting enzyme inhibitors (ACEIs and angiotensin receptor blockers (ARBs in CIN is controversial. They have been reported to be effective in the prevention of CIN in previous studies, but some studies have concluded that they were associated with an increased risk of CIN, especially in patients with pre-existing renal impairment. In summary, there is no solid data to link ACE inhibitors and ARB to CIN, and larger randomised controlled trials are necessary to further investigate their role in the development of CIN. In this review, we discuss the pathophysiology of CIN, the role of RAAS on the development of CIN, and the effect of RAAS blockers on CIN.

  18. Angiotensin Converting Enzyme Inhibitor-related Angioedema: A Case of an Unexpected Death

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    Eray Atalay

    2015-11-01

    Full Text Available Angioedema is an asymmetric non-pitting oedema on face, lips, tongue and mucous membranes; any delay in diagnosis and treatment can be fatal. Treatment with lisinopril as an angiotensin converting enzyme (ACE inhibitor, can be a reason of angioedema. Here we report a case who developed oral-facial edema four years after using lisinopril/hydrochlorothiazide. Laryngeal oedema is a main cause of death in angioedema. The treatment of choice in angioedema including fresh frozen plasma, C1 inhibitor concentrations and BRK-2 antagonists (bradykinin B2 receptor antagonists were used. In this case; a 77 years old female patient suffering from hypertension was considered. This patient was suffering two days from swelling on her face and neck. Non- allergic angioedema was distinguished in five major forms; acquired (AAO, hereditary (HAE, renin-angiotensin-aldosterone system (RAAS blocker-dependent, pseudoallergic angioedema (PAS and an idiopathic angioedema (IAO. She was admitted to our clinic with the diagnosis of hereditary angioedema. Patient had skin edema and life threatening laryngeal edema. In emergency department treatment was started using intravenous methylprednisolone, diphenydramine as well as inhaled and subcutaneous epinephrine simultaneously. Despite the initial treatment, the patient died due to the insufficient respiration and cardiac arrest. The patient has no history of kidney disease.

  19. Angiotensin Converting Enzyme Inhibitor-related Angioedema: A Case of an Unexpected Death.

    Science.gov (United States)

    Atalay, Eray; Özdemir, Mehmet Tamer; Çiğsar, Gülşen; Omurca, Ferhat; Aslan, Nurullah; Yildiz, Mehmet; Gey, Zehra Bahar

    2015-12-01

    Angioedema is an asymmetric non-pitting oedema on face, lips, tongue and mucous membranes; any delay in diagnosis and treatment can be fatal. Treatment with lisinopril as an angiotensin converting enzyme (ACE) inhibitor, can be a reason of angioedema. Here we report a case who developed oral-facial edema four years after using lisinopril/hydrochlorothiazide. Laryngeal oedema is a main cause of death in angioedema. The treatment of choice in angioedema including fresh frozen plasma, C1 inhibitor concentrations and BRK-2 antagonists (bradykinin B2 receptor antagonists) were used. In this case; a 77 years old female patient suffering from hypertension was considered. This patient was suffering two days from swelling on her face and neck. Non- allergic angioedema was distinguished in five major forms; acquired (AAO), hereditary (HAE), renin-angiotensin-aldosterone system (RAAS) blocker-dependent, pseudoallergic angioedema (PAS) and an idiopathic angioedema (IAO). She was admitted to our clinic with the diagnosis of hereditary angioedema. Patient had skin edema and life threatening laryngeal edema. In emergency department treatment was started using intravenous methylprednisolone, diphenydramine as well as inhaled and subcutaneous epinephrine simultaneously. Despite the initial treatment, the patient died due to the insufficient respiration and cardiac arrest. The patient has no history of kidney disease.

  20. The Divergent Cardiovascular Effects of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Myocardial Infarction and Death.

    Science.gov (United States)

    Strauss, Martin H; Hall, Alistair S

    2016-01-01

    The renin angiotensin aldosterone system (RAAS) plays a central role in the pathophysiology of hypertension and vascular disease. Angiotensin converting enzyme inhibitors (ACEis) suppress angiotensin II (ANG II) concentrations, whereas angiotensin receptor blockers (ARBs) block the binding of ANG II to AT1 receptors. ACEis and ARBs are both effective anti-hypertensive agents and have similar risk reductions in stroke - a blood pressure dependent phenomenon. ACEis also reduce the risk of myocardial infarction (MI) and mortality in high risk hypertensive patients, as well as in diabetics, the elderly, those with vascular disease, and in congestive heart failure. ARBs, in contrast, do not reduce the risk of MI or death in clinical trials where the comparator has been another active therapy or even a placebo. Systematic reviews of ARBs that include meta-analyses or meta-regression analyses confirm that ARBs lack the cardiovascular protective effects of ACEis, which in part are "independent" of blood pressure lowering. Practice guidelines, especially those in high risk hypertensive patients, should reflect the evidence that ACEis and ARBs have divergent cardiovascular effects - ACEis reduce mortality, whereas ARBs do not. ACEis should be the preferred RAAS inhibitor in high risk patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Angiotensin-converting enzyme inhibitors in the therapy of renal diseases.

    Science.gov (United States)

    Lefebvre, H P; Toutain, P L

    2004-10-01

    Renal diseases, especially chronic renal failure (CRF), are common in canine and feline medicine. The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in these conditions in the development of renal lesions and the progression of kidney dysfunction. Angiotensin-converting enzyme inhibitors (ACEI) are currently considered as the most efficient agents in therapeutic strategies. The benefit of an ACEI treatment can be explained by at least three mechanisms: ACEI limit systemic and glomerular capillary hypertension, have an antiproteinuric effect, and retard the development of glomerulosclerosis and tubulointerstitial lesions. These effects have been studied in dogs and cats, and there is now some evidence to support the recommendation of ACEI therapy in dogs and cats with CRF. Nevertheless the prescription of ACEI in such patients should take into account the potential influence of renal impairment on ACEI disposition, and adverse effects on the renal function itself (especially hypotension and acute reductions in glomerular filtration rate). The risk of drug interaction with diuretics, nonsteroidal anti-inflammatory drugs and anesthetics, should not be overestimated. Furthermore, hypotension may occur in patients on a low sodium diet.

  2. Effects Of The Direct Renin Inhibitor Aliskiren On Oxidative Stress In Isolated Rat Heart

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    Plecevic Sasa

    2015-09-01

    Full Text Available Increased activity of the renin-angiotensin-aldosterone system (RAAS plays a significant role in the development and progression of various cardio-metabolic diseases, such as hypertension, atherosclerosis and heart failure. Aliskiren is the newest antihypertensive drug and the first orally active direct renin inhibitor to become available for clinical use. This study investigated the acute and direct effects of Aliskiren on different parameters of oxidative stress on isolated rat heart. The hearts of male Wistar albino rats (n = 24, 8 per experimental group, age 8 weeks, body mass 180–200 g, were excised and retrogradely perfused according to the Langendorfftechnique at a gradually increasing perfusion pressure (40-120 cmH2O. Markers of oxidative stress (NO2−, TBARS, H2O2 and O2− were measured spectrophotometrically after perfusion with three different concentrations of Aliskiren (0.1 μM, 1 μM, and 10 μM. The results demonstrated possible dose-dependent cardioprotective properties of Aliskiren, particularly with higher CPP. Lipid peroxidation (TBARS levels decreased with the highest dose of Aliskiren and higher CPP, and the same trend was observed in nitrite (NO2− and hydrogen peroxide (H2O2 levels. These findings indicate that the acute effects of Aliskiren do not likely promote the production of reactive oxygen species upon higher pressure with the highest dose. Aliskiren may exert beneficial effects on oxidative stress biomarkers.

  3. Aliskiren: Just a New Drug for Few Selected Patients or an Innovative Molecule Predestinated to Replace Arbs and Ace-Inhibitors?

    Directory of Open Access Journals (Sweden)

    Elena Raccuglia

    2009-11-01

    Full Text Available The renin-angiotensin-aldosterone system (RAAS plays a dominant role in the pathophysiology of hypertension, diabetes mellitus, chronic kidney disease and chronic heart failure. Therefore, drugs that block key components of the RAAS such as ACE inhibitors (ACEI and angiotensin receptor blockers (ARBs have gained wide clinical use for these indications. Despite progress, the morbidity and mortality of patients treated with ACEI or ARBs remain high. Aliskiren (Tekturna, Rasilez is the first orally active inhibitor of renin approved for clinical use as an antihypertensive agent. The development program has established that at the licensed doses of 150 mg and 300 mg. Aliskiren is effective either as monotherapy or in combination with drugs from the other major classes. In this review we analyze and review the information already gained with Aliskiren, raises questions regarding the advantages of DRIs as monotherapy compared to marketed ACEIs and ARBs, their potential added value in combination with other RAAS modulators and other still unproven benefits in relation to prorenin and renin receptor biology.

  4. Effects of a novel ACE inhibitor, 3-(3-thienyl)-l-alanyl-ornithyl-proline, on endothelial vasodilation and hepatotoxicity in l-NAME-induced hypertensive rats.

    Science.gov (United States)

    Seth, Mahesh Kumar; Hussain, M Ejaz; Pasha, Santosh; Fahim, Mohammad

    2016-01-01

    Nitric oxide (NO) is a widespread biological mediator involved in many physiological and pathological processes, eg, in the regulation of vascular tone and hypertension. Chronic inhibition of NO synthase by N(G)-nitro-l-arginine methyl ester (l-NAME) hydrochloride results in the development of hypertension accompanied by an increase in vascular responsiveness to adrenergic stimuli. Recently, we developed a novel sulfur-containing angiotensin-converting enzyme inhibitor: 3-(3-thienyl)-l-alanyl-ornithyl-proline (TOP). Our previous studies indicated a superior nature of the molecule as an antihypertensive agent in spontaneously hypertensive rats (showing the involvement of renin-angiotensin-aldosterone system) in comparison to captopril. The aim of the present study was to investigate the effect of TOP on NO pathway in l-NAME-induced hypertensive rats, and captopril was included as the standard treatment group. Treatment with both TOP (20 mg/kg) and captopril (40 mg/kg) prevented the development of hypertension in l-NAME model, but TOP showed better restoration of NO and normal levels of angiotensin-converting enzyme. In addition, in vitro vasorelaxation assay showed an improvement in endothelium-dependent vasodilation in both the cases. Further, the biochemical (malondialdehyde, alanine aminotransferase, and aspartate aminotransferase) and the histopathological effects of TOP on rat liver tissues revealed a protective nature of TOP in comparison to captopril in the l-NAME model. In conclusion, TOP at 50% lesser dose than captopril was found to be better in the l-NAME model.

  5. Effect of Renin-Angiotensin-Aldosterone 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

    Science.gov (United States)

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

    2012-01-01

    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 therapeutic interventions is associated with decreased urinary KIM-1 levels. Study Design Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover trial. Setting & Participants 34 proteinuric patients without diabetes from our outpatient renal clinic. Intervention Stepwise 6-week interventions of losartan, sodium restriction (low-sodium [LS] diet), their combination, losartan plus hydrochlorothiazide (HCT), and the latter plus an LS diet. Outcomes & Measurements Urinary excretion of KIM-1, total protein, and N-acetyl-β-D-glucosaminidase (NAG) as a positive control for tubular injury. Results Mean baseline urine protein level was 3.8 ± 0.4 (SE) g/d, and KIM-1 level was 1,706 ± 498 ng/d (increased compared with healthy controls; 74 ng/d). KIM-1 level was decreased by using placebo/LS (1,201 ± 388 ng/d; P = 0.04), losartan/high sodium (1,184 ± 296 ng/d; P = 0.09), losartan/LS (921 ± 176 ng/d; P = 0.008), losartan/high sodium plus HCT (862 ± 151 ng/d; P = 0.008) and losartan/LS plus HCT (743 ± 170 ng/d; P = 0.001). The decrease in urinary KIM-1 levels paralleled the decrease in proteinuria (R = 0.523; P < 0.001), but not blood pressure or creatinine clearance. 16 patients reached target proteinuria with protein less than 1 g/d, whereas KIM-1 levels normalized in only 2 patients. Urinary NAG level was increased at baseline and significantly decreased during the treatment periods of combined losartan plus HCT only. The decrease in urinary NAG levels was not closely related to proteinuria. Limitations Post hoc analysis. Conclusions Urinary KIM-1 level was increased in patients with nondiabetic CKD with proteinuria and decreased in parallel with proteinuria by using losartan, sodium restriction, their combination, losartan plus HCT, and the latter plus sodium restriction. These results are consistent with the hypothesis of amelioration of proteinuria-induced tubular damage. Long-term studies are warranted to evaluate whether targeting treatment on KIM-1 can improve outcomes in patients with CKD with proteinuria. PMID:18823687

  6. 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 an

  7. ALISKIREN (RENIN INHIBITOR AS THE RECENT ANTIHYPERTENSIVE MODALITY

    Directory of Open Access Journals (Sweden)

    Luh Gde Primahatini Suaka Putri

    2013-12-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Hypertension is a chronic disease which is commonly found. Many people pay attention on it. The prevalence of hypertension all over the world is almost one billion, of which mortality is approximately 1,7 million each year. The renin-angiotensin-aldosterone system (RAAS has an important role which caused hypertension. Two kind of drugs which work on RAAS and recently used widely are angiotensin-converting enzyme inhibitors (ACEI and angiotensin receptor blocker (ARB. Both of them have weakness in blocking RAAS and their side effects. Renin is an important component in RAAS and has specificity for angiotensinogen. Renin inhibitors can block RAAS at the highest level. Aliskiren is the first renin inhibitor which can be orally given and has developed until the clinical trial of the third phase. The disadvantages of ACEI and ARB can be solved because of the aliskiren. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study

    DEFF Research Database (Denmark)

    Krum, Henry; Massie, Barry; Abraham, William T

    2011-01-01

    AIMS: The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs) ...

  14. Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease

    NARCIS (Netherlands)

    de Zeeuw, Dick; Akizawa, Tadao; Audhya, Paul; Bakris, George L.; Chin, Melanie; Christ-Schmidt, Heidi; Goldsberry, Angie; Houser, Mark; Krauth, Melissa; Heerspink, Hiddo J. Lambers; McMurray, John J.; Meyer, Colin J.; Parving, Hans-Henrik; Remuzzi, Giuseppe; Toto, Robert D.; Vaziri, Nosratola D.; Wanner, Christoph; Wittes, Janet; Wrolstad, Danielle; Chertow, Glenn M.

    2013-01-01

    Background 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. Methods We randomly assigned 2185

  15. Ideas for Hypertensive Experimental Study Prevented and Treated by TCM

    Institute of Scientific and Technical Information of China (English)

    王振涛

    2004-01-01

    Hypertensive experimental studies prevented and treated by TCM are matured relevant studies of western medicine for reference, such as the hypotensive effect and elucidating its therapeutic mechanism. Comprehension in all literatures, most simple herbs and compound recipes show functions such as: Adjustment of renin-angiotensin-aldosterone system (RAAS), like angiotensin converting enzyme inhibitor (ACEI);

  16. Ideas for Hypertensive Experimental Study Prevented and Treated by TCM

    Institute of Scientific and Technical Information of China (English)

    王振涛

    2004-01-01

    @@ Hypertensive experimental studies prevented and treated by TCM are matured relevant studies of western medicine for reference,such as the hypotensive effect and elucidating its therapeutic mechanism.Comprehension in all literatures, most simple herbs and compound recipes show functions such as: Adjustment of renin-angiotensin-aldosterone system (RAAS), like angiotensin converting enzyme inhibitor (ACEI);

  17. Sodium intake, RAAS-blockade and progressive renal disease

    NARCIS (Netherlands)

    de Borst, Martin H; Navis, Gerjan

    2016-01-01

    Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the current standard treatment to prevent progressive renal function loss in patients with chronic kidney disease. Yet in many patients the rena

  18. Aliskiren combined with losartan in type 2 diabetes and nephropathy

    DEFF Research Database (Denmark)

    2008-01-01

    BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries. We evaluated the renoprotective effects of dual blockade of the renin-angiotensin-aldosterone system by adding treatment with aliskiren, an oral direct renin inhibitor, to treatment with the m...

  19. Sodium intake, RAAS-blockade and progressive renal disease

    NARCIS (Netherlands)

    de Borst, Martin H; Navis, Gerjan

    2016-01-01

    Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the current standard treatment to prevent progressive renal function loss in patients with chronic kidney disease. Yet in many patients the rena

  20. New roles for renin and prorenin in heart failure and cardiorenal crosstalk

    NARCIS (Netherlands)

    Schroten, Nicolas F.; Gaillard, Carlo A. J. M.; van Veldhuisen, Dirk J.; Szymanski, Mariusz K.; Hillege, Hans L.; de Boer, Rudolf A.

    2012-01-01

    The renin-angiotensin-aldosterone-system (RAAS) plays a central role in the pathophysiology of heart failure and cardiorenal interaction. Drugs interfering in the RAAS form the pillars in treatment of heart failure and cardiorenal syndrome. Although RAAS inhibitors improve prognosis, heart failure-a

  1. Sodium intake, RAAS-blockade and progressive renal disease

    NARCIS (Netherlands)

    de Borst, Martin H; Navis, Gerjan

    Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the current standard treatment to prevent progressive renal function loss in patients with chronic kidney disease. Yet in many patients the

  2. The Relationship between Renin-Angiotension-Aldosterone System and Certain Infectious Diseases%肾素-血管紧张素-醛固酮系统与某些传染病的关系

    Institute of Scientific and Technical Information of China (English)

    孙志坚; 黄湘虎; 唐季和

    1986-01-01

    @@ 肾素-血管紧张素-醛固酮系统(Renin-angiotensin-aldosterone system,RAAS)在维持体液和电解质平衡、调节血压、稳定内环境等方面起着重要的作用.在休克、应激、失水、电解质紊乱及某些传染病发病过程中,RAAS常处于兴奋状态,并可引起严重的后果,现将有关问题分述于后.

  3. A Transgenic Platform for Testing Drugs Intended for Reversal of Cardiac Remodeling Identifies a Novel 11βHSD1 Inhibitor Rescuing Hypertrophy Independently of Re-Vascularization

    Science.gov (United States)

    Gilon, Dan; Gruener, Sabine; Pietranico-Cole, Sherrie; Oppenheim, Amit; Keshet, Eli

    2014-01-01

    Rationale Rescuing adverse myocardial remodeling is an unmet clinical goal and, correspondingly, pharmacological means for its intended reversal are urgently needed. Objectives To harness a newly-developed experimental model recapitulating progressive heart failure development for the discovery of new drugs capable of reversing adverse remodeling. Methods and Results A VEGF-based conditional transgenic system was employed in which an induced perfusion deficit and a resultant compromised cardiac function lead to progressive remodeling and eventually heart failure. Ability of candidate drugs administered at sequential remodeling stages to reverse hypertrophy, enlarged LV size and improve cardiac function was monitored. Arguing for clinical relevance of the experimental system, clinically-used drugs operating on the Renin-Angiotensin-Aldosterone-System (RAAS), namely, the ACE inhibitor Enalapril and the direct renin inhibitor Aliskerin fully reversed remodeling. Remodeling reversal by these drugs was not accompanied by neovascularization and reached a point-of-no-return. Similarly, the PPARγ agonist Pioglitazone was proven capable of reversing all aspects of cardiac remodeling without affecting the vasculature. Extending the arsenal of remodeling-reversing drugs to pathways other than RAAS, a specific inhibitor of 11β-hydroxy-steroid dehydrogenase type 1 (11β HSD1), a key enzyme required for generating active glucocorticoids, fully rescued myocardial hypertrophy. This was associated with mitigating the hypertrophy-associated gene signature, including reversing the myosin heavy chain isoform switch but in a pattern distinguishable from that associated with neovascularization-induced reversal. Conclusions A system was developed suitable for identifying novel remodeling-reversing drugs operating in different pathways and for gaining insights into their mechanisms of action, exemplified here by uncoupling their vascular affects. PMID:24667808

  4. Development Review of Direct Renin Inhibitors%直接肾素抑制剂的临床应用前景

    Institute of Scientific and Technical Information of China (English)

    吴光哲; 贾建华; 王岩

    2011-01-01

    肾素-血管紧张素-醛固酮系统是药物治疗心血管系统疾病的关键作用靶点.阻断肾素-血管紧张素系统的病理生理作用可以从三个位点进行:血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体拮抗剂和肾素抑制剂.近年研究表明直接肾素抑制剂比血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂具有更多的潜在获益和更好的耐受性.现就直接肾素抑制剂药物阿利吉伦的应用前景进行综述.%The renin angiotensin aldosterone system is a target for drugs combating cardiovascular disease. Pharmacological interruption of the renin-angiotensin system is possible at three major sites, the angiotensin-converting enzyme, the AT, receptor and at the interaction of renin with its substrate. Direct renin inhibitors represent an alternative strategy for inhibiting the renin-angiotensin system. They have a mechanism of action different from that of angiotensin converting enzyme inhibitors and AT, receptor blockers. This article reviews the development of oral renin inhibitors and their pharmaeokinetic and pharmacodynamic properties, with a focus on aliskiren.

  5. Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

    Science.gov (United States)

    Raebel, Marsha A

    2012-06-01

    The aims of this article are to review the current understanding of hyperkalemia associated with angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy. This includes reviewing the pathophysiology of how these agents affect potassium handling within the kidney, risk factors for developing hyperkalemia, incidence, clinical signs and symptoms, and providing a practical approach to treatment of the patient who is either at risk of, or experiencing, hyperkalemia. ACEi and ARB are effective therapeutic agents used in a variety of clinical scenarios. However, related to their effects on the renin-angiotensin-aldosterone system, their use can be associated with hyperkalemia, particularly in patients who have chronic renal insufficiency. Published incidence estimates of hyperkalemia associated with ACEi or ARB vary, but up to 10% of patients may experience at least mild hyperkalemia. Important considerations when initiating ACEi or ARB therapy include obtaining an estimate of glomerular filtration rate and a baseline serum potassium concentration, as well as assessing whether the patient has excessive potassium intake from diet, supplements, or drugs that can also increase serum potassium. Serum potassium monitoring shortly after initiation of therapy can assist in preventing hyperkalemia. If hyperkalemia does develop, prompt recognition of cardiac dysrhythmias and effective treatment to antagonize the cardiac effects of potassium, redistribute potassium into cells, and remove excess potassium from the body is important.Understanding the mechanism of action of ACEi and ARB coupled with judicious drug use and clinical vigilance can minimize the risk to the patient of developing hyperkalemia. Should hyperkalemia occur, prompt recognition and management can optimize clinical outcome.

  6. DPP-4 Inhibitors as Therapeutic Modulators of Immune Cell Function and Associated Cardiovascular and Renal Insulin Resistance in Obesity and Diabetes.

    Science.gov (United States)

    Aroor, Annayya; McKarns, Susan; Nistala, Ravi; Demarco, Vincent; Gardner, Michael; Garcia-Touza, Mariana; Whaley-Connell, Adam; Sowers, James R

    2013-04-01

    The prevalence of obesity and diabetes continues to rise in the United States and worldwide. These findings parallel the expansion of childhood obesity and diabetes. Obesity is a central component of the cardiorenal metabolic syndrome (CRS) which increases the risk for cardiovascular disease (CVD) and chronic kidney disease (CKD). The hallmark of obesity, CRS, and early type 2 diabetes is insulin resistance, a result of decreased insulin metabolic signaling due, in part, to enhanced serine phosphorylation and/or proteasome-mediated degradation of the insulin receptor substrate. Cardiovascular and renal insulin resistance significantly contributes to endothelial dysfunction, impaired cardiac diastolic and vascular relaxation, glomerular injury, and tubular dysfunction. In this context, multiple factors including oxidative stress, increased inflammation, and inappropriate activation of the renin-angiotensin-aldosterone and the sympathetic nervous system contribute to overweight- and obesity-induced systemic and tissue insulin resistance. One common link between obesity and the development of insulin resistance appears to be a low-grade inflammatory response resulting from dysfunctional innate and adaptive immunity. In this regard, there has been recent work on the role of dipeptidyl peptidase-4 (DPP-4) in modulating innate and adaptive immunity. The direct effects of DPP-4 on immune cells and the indirect effects through GLP-1-dependent and -independent pathways suggest effects of DPP-4 inhibition may have beneficial effects beyond glycemic control in improving CVD and renal outcomes. Accordingly, this review addresses new insights into the role of DPP-4 in immune modulation and the potential beneficial effects of DPP-4 inhibitors in insulin resistance and associated CVD and CKD prevention.

  7. Impact of losartan and angiotensin II on the expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rat vascular smooth muscle cells.

    Science.gov (United States)

    Guo, Yan-Song; Wu, Zong-Gui; Yang, Jun-Ke; Chen, Xin-Jing

    2015-03-01

    The present study aimed to investigate the impact of losartan and angiotensin II (AngII) on the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), secreted by rat vascular smooth muscle cells (VSMCs). Rat VSMCs were isolated and cultured in different concentrations of AngII and losartan for 24 h and western blot analysis and quantitative polymerase chain reaction were performed to observe the subsequent impact on the gene and protein expression of MMP-9 and TIMP-1. AngII was shown to promote the protein and gene expression of MMP-9 in VSMCs in a concentration-dependent manner. No effect was observed on the expression of TIMP-1, therefore, an increase in the MMP-9/TIMP-1 ratio was observed. Losartan was shown to be able to inhibit MMP-9 protein and gene expression in a concentration-dependent manner, whilst promoting an increase in TIMP-1 expression, thus decreasing the ratio of MMP-9/TIMP-1. The combined action of losartan and AngII resulted in the same directional changes in MMP-9 and TIMP-1 expression as observed for losartan alone. The comparison of AngII, losartan and the combinatory effect on the expression of MMP-9 and TIMP-1 in VSMCs indicated that losartan inhibited the effects of AngII, therefore reducing the MMP-9/TIMP-1 ratio, which may contribute to the molecular mechanism of losartan in preventing atherosclerosis. In atherosclerosis, the development of the extracellular matrix of plaque is closely correlated with the evolution of AS. The balance between MMPs and TIMPs is important in maintaining the dynamic equilibrium between the ECM, and the renin-angiotensin-aldosterone system, which is involved in the pathologenesis of AS, and in which AngII has a central role.

  8. Angiotensin receptor blockers (ARB) outperform angiotensin-converting enzyme (ACE) inhibitors on ischemic stroke prevention in patients with hypertension and diabetes - A real-world population study in Taiwan.

    Science.gov (United States)

    Pai, Pei-Ying; Muo, Chih-Hsin; Sung, Fung-Chang; Ho, Hung-Chi; Lee, Yuan-Teh

    2016-07-15

    Combination therapy with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) has been stressed for its comprehensive blocking of the renin-angiotensin-aldosterone system, but the evidence for their respective safety and efficacy, in particular with stroke prevention, is still insufficient in population-based follow-up studies in the real world. Using Taiwan's National Health Insurance claims data, we identified 5445 subjects aged 18years and older who had newly diagnosed hypertension in 1997-2010, from them diagnosed type 2 diabetes later. Among them, 2161 patients took ACEI, 1703 patients took ARB, 165 patients took both ACEI and ARB, and 1416 patients had neither. During the follow-up period, the stroke incidence density was the lowest (23.02 per 1000person-years) in ARB group, followed by the group with neither medication, the ACEI group, and ARB/ACEI combination group (24.06, 30.23, and 37.86 per 1000person-years, respectively). Compared with patients taking neither medication, the adjusted hazard ratios (HRs) were 1.27 (95% CI 1.02-1.58) for ACEI group, 0.95 (95% CI 0.74-1.22) for ARB group, and 1.56 (95% CI 0.99-2.47) for ARB/ACEI combined group. Greater reduction in risk of stroke was observed in patients with high dose ARB (adjusted HR=0·42, 95% CI 0·24-0·75). Our findings support the practice that ARBs could be used, from the perspective of stroke prevention, as a first-line antihypertensive drug for patients with both hypertension and diabetes. The group with ARB regimen reduces 26% of stroke in contrast to the group with ACEI regimen. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. [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.

  10. 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...

  11. 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-American...

  12. Hyperkalemia in Heart Failure.

    Science.gov (United States)

    Sarwar, Chaudhry M S; Papadimitriou, Lampros; Pitt, Bertram; Piña, Ileana; Zannad, Faiez; Anker, Stefan D; Gheorghiade, Mihai; Butler, Javed

    2016-10-01

    Disorders of potassium homeostasis can potentiate the already elevated risk of arrhythmia in heart failure. Heart failure patients have a high prevalence of chronic kidney disease, which further heightens the risk of hyperkalemia, especially when renin-angiotensin-aldosterone system inhibitors are used. Acute treatment for hyperkalemia may not be tolerated in the long term. Recent data for patiromer and sodium zirconium cyclosilicate, used to treat and prevent high serum potassium levels on a more chronic basis, have sparked interest in the treatment of hyperkalemia, as well as the potential use of renin-angiotensin-aldosterone system inhibitors in patients who were previously unable to take these drugs or tolerated only low doses. This review discusses the epidemiology, pathophysiology, and outcomes of hyperkalemia in heart failure; provides an overview of traditional and novel ways to approach management of hyperkalemia; and discusses the need for further research to optimally treat heart failure.

  13. Splanchnic and systemic hemodynamic derangement in decompensated cirrhosis

    DEFF Research Database (Denmark)

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

    2001-01-01

    significance to the low systemic vascular resistance and abnormal volume distribution of blood, which are important elements in the development of the concomitant cardiac dysfunction, recently termed 'cirrhotic cardiomyopathy'. Systolic and diastolic functions are impaired with direct relation to the degree...... in vasodilation and increased arterial compliance. Reflex-induced, enhanced sympathetic nervous system activity, activation of the renin-angiotensin aldosterone system, and elevated circulation vasopressin and endothelin-1 are implicated in hemodynamic counter-regulation in cirrhosis. Recent research has focused......Patients with cirrhosis and portal hypertension exhibit characteristic hemodynamic changes with hyperkinetic systemic circulation, abnormal distribution of blood volume and neurohumoral dysregulation. Their plasma and noncentral blood volumes are increased. Splanchnic vasodilation is of pathogenic...

  14. The role of the sympathetic nervous system in obesity-related hypertension.

    Science.gov (United States)

    da Silva, Alexandre A; do Carmo, Jussara; Dubinion, John; Hall, John E

    2009-06-01

    Obesity is recognized as a major health problem throughout the world. Excess weight is a major cause of increased blood pressure in most patients with essential hypertension and greatly increases the risk for diabetes, cardiovascular diseases, and end-stage renal disease. Although the mechanisms by which obesity raises blood pressure are not completely understood, increased renal sodium reabsorption, impaired pressure natriuresis, and volume expansion appear to play important roles. Several potential mechanisms have been suggested to contribute to altered kidney function and hypertension in obesity, including activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system, as well as physical compression of the kidneys, especially when visceral obesity is present. Activation of the sympathetic nervous system in obesity may be due, in part, to hyperleptinemia and other factors secreted by adipocytes and the gastrointestinal tract, activation of the central nervous system melanocortin pathway, and baroreceptor dysfunction.

  15. Losartan降压效应及对高血压病患者血浆肾素、血管紧张素Ⅱ、醛固酮水平的影响%Effects of iosartan on blood pressure and plasma renin-angiotensin-aldosterone system in hypertensive patients.

    Institute of Scientific and Technical Information of China (English)

    吕湛; 王周碧; 陈运贞; 邓国兰

    2001-01-01

    目的探讨AngⅡ受体拮抗剂Losartan对EH患者的降压效应及血浆RAAS的影响.方法 1~3级高血压病患者65例,给予Losartan 50mg/d治疗8周,分别于治疗前、后测量患者血压、心率.并分别于治疗前、1周、8周时用放射免疫法测定血浆PRA、AngⅡ、Ald活性.结果(①Losartan对1~3级高血压患者SBP、DBP均有下降作用,降压同时心率不增快.②Losartan治疗1周时血浆PRA、AngⅡ显著高于治疗前(P<0.05或P<0.01).A1d则较治疗前降低(P<0.05).8周时PRA、AngⅡ仅轻度升高与治疗前相比差异无显著性(P>0.05),Ald则较1周时有进一步下降,但无显著性(P>0.05).结论①Losartan 50mg/d能有效降低不同程度的SBP、DBP,降压同时心率无反射性增加.②长期服用Losartan不会引起血浆PRA、AngⅡ持久异常增高,而AId还会显著下降.

  16. Angiotensine converting enzyme inhibitors In acute myocardial infarction--a review.

    Science.gov (United States)

    Sawhney, J P S

    2011-01-01

    Coronary artery diseases (CADs) are preventable and controllable disorders, but they continue to be a major cause of morbidity and premature mortality across globe. India is projected to have 62 million CAD patients by 2015, with nearly 1/3rd of this burden shared by patients younger than 40 years. The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in blood pressure (BP) regulation and fluid and electrolyte homoeostasis. Activation of RAAS has long been implicated in the pathogenesis of acute myocardial infarction (AMI) and benefits of inhibition of RAAS as an effective way to intervene in the pathogenesis of AMI is well documented. In the setting of AMI, angiotensin-II plays a significant detrimental role, contributing to cardiac remodeling, a process that predisposes to subsequent arrhythmia and cardiac failure. Angiotensin converting enzyme inhibitors (ACEls) play a key role in the clinical management of several cardiovascular disease (CVD)s such as AMI, by inhibiting the actions of angiotensin-II, ACEIs would be expected to modify unwanted post-AMI events. ACEIs trials have tested AMI patients with two different approaches: selective (those with left ventricular dysfunction (LVD) treated over a long-term) and relatively unselective (those treated early over the course and for a short-period, up to 6 weeks). In general, results are consistent and beneficial as regards to reduction in both short-term & long-term mortality and heart failure. There are evidences that suggest yielding of an extra protection (reduced mortality and occurrence of severe LVD) with early introduction of ACEIs in the course of AMI. Trials have also shown ACEIs effective and consistent protection against re-infarction and management of arrhythmias after AMI. Large clinical trials have proven ACEIs to be superior to ARB, in preventing CV deaths in high-risk AMI subjects. They have proven to be safe & effective in diabetic & older population. With wealth of evidence

  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. 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...

  19. Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Afzelius, Pia; Bazeghi, Nassim; Bie, Peter;

    2011-01-01

    Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development...

  20. Sodium restriction potentiates the renoprotective effects of combined vitamin D receptor activation and angiotensin-converting enzyme inhibition in established proteinuric nephropathy

    NARCIS (Netherlands)

    Mirkovic, Katarina; Frenay, Anne-Roos S; van den Born, Jacob; van Goor, Harry; Navis, Gerjan; de Borst, Martin H

    2015-01-01

    BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) blockade provides renoprotective effects in chronic kidney disease (CKD); yet progressive renal function loss remains common. Dietary sodium restriction potentiates the renoprotective effects of RAAS blockade. Vitamin D receptor activator (VDRA

  1. Genome-Wide Meta-Analyses of Plasma Renin Activity and Concentration Reveal Association with the Kininogen 1 and Prekallikrein Genes

    NARCIS (Netherlands)

    Lieb, Wolfgang; Chen, Ming-Huei; Teumer, Alexander; de Boer, Rudolf A; Lin, Honghuang; Fox, Ervin R; Musani, Solomon K; Wilson, James G; Wang, Thomas J; Völzke, Henry; Petersen, Ann-Kristin; Meisinger, Christine; Nauck, Matthias; Schlesinger, Sabrina; Li, Yong; Ménard, Joël; Hercberg, Serge; Wichmann, H-Erich; Völker, Uwe; Rawal, Rajesh; Bidlingmaier, Martin; Hannemann, Anke; Dörr, Marcus; Rettig, Rainer; van Gilst, Wiek H; van Veldhuisen, Dirk J; Bakker, Stephan J L; Navis, Gerjan; Wallaschofski, Henri; Meneton, Pierre; van der Harst, Pim; Reincke, Martin; Vasan, Ramachandran S

    2015-01-01

    BACKGROUND: -The renin-angiotensin-aldosterone-system (RAAS) is critical for regulation of blood pressure and fluid balance and influences cardiovascular remodeling. Dysregulation of the RAAS contributes to cardiovascular and renal morbidity. The genetic architecture of circulating RAAS components i

  2. Vitamin D receptor activator and dietary sodium restriction to reduce residual urinary albumin excretion in chronic kidney disease (ViRTUE study) : rationale and study protocol

    NARCIS (Netherlands)

    Keyzer, Charlotte A.; de Jong, Maarten A.; van Breda, G. Fenna; Vervloet, Marc G.; Laverman, Gozewijn D.; Hemmelder, Marc; Janssen, Wilbert M.; Heerspink, Hiddo J. Lambers; Navis, Gerjan; de Borst, Martin H.

    Optimal albuminuria reduction is considered essential to halting chronic kidney disease (CKD) progression. Both vitamin D receptor activator (VDRA) treatment and dietary sodium restriction potentiate the efficacy of renin-angiotensin-aldosterone- system (RAAS) blockade to reduce albuminuria. The

  3. 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....

  4. Levels of NT-proBNP, markers of low-grade inflammation, and endothelial dysfunction during spironolactone treatment in patients with diabetic kidney disease

    DEFF Research Database (Denmark)

    Nielsen, Stine; Schjoedt, Katrine J; Rossing, Kasper;

    2013-01-01

    Renin-angiotensin-aldosterone system (RAAS) blockade may reduce levels of biomarkers of chronic low-grade inflammation and endothelial dysfunction. We investigated the effect of spironolactone added to standard RAAS blockade on these biomarkers in an analysis of four original studies. MATERIALS...... AND METHODS: The studies were double-blind, randomised, placebo-controlled studies in 46 type 1 and 23 type 2 diabetic patients with micro- or macroalbuminuria treated with angiotensin-converting enzyme inhibitor (ACE inhibitor) or angiotensin receptor blocker (ARB), and randomised to additional treatment...

  5. New Insight into the Molecular Drug Target of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Vivian Soetikno

    2014-01-01

    Full Text Available Diabetic nephropathy (DN lowered quality of life and shortened life expectancy amongst those affected. Evidence indicates interaction between advanced glycation end products (AGEs, activated protein kinase C (PKC and angiotensin II exacerbate the progression of DN. Inhibitors of angiotensin-converting enzyme (ACEIs, renin angiotensin aldosterone system (RAAS, AGEs, and PKC have been tested for slowing down the progression of DN. The exact molecular drug targets that lead to the amelioration of renal injury in DN are not well understood. This review summarizes the potential therapeutic targets, based on putative mechanism in the progression of the disease.

  6. Acid-base and electrolyte abnormalities in heart failure: pathophysiology and implications.

    Science.gov (United States)

    Urso, Caterina; Brucculeri, Salvatore; Caimi, Gregorio

    2015-07-01

    Electrolyte and acid-base abnormalities are a frequent and potentially dangerous complication in subjects with congestive heart failure. This may be due either to the pathophysiological alterations present in the heart failure state leading to neurohumoral activation (stimulation of the renin-angiotensin-aldosterone system, sympathoadrenergic stimulation), or to the adverse events of therapy with diuretics, cardiac glycosides, and ACE inhibitors. Subjects with heart failure may show hyponatremia, magnesium, and potassium deficiencies; the latter two play a pivotal role in the development of cardiac arrhythmias. The early identification of these alterations and the knowledge of the pathophysiological mechanisms are very useful for the management of these patients.

  7. 替米沙坦与雷米普利联用对慢性心力衰竭患者肾素-血管紧张素-醛固酮系统及心室重塑的影响%Effects of Combined Telmisartan and Ramlpril on Heart Function and Renin-angiotensin-aldosterone System and Ventricle Remodeling in Patients with Chronic Congestive Heart Failure

    Institute of Scientific and Technical Information of China (English)

    毋淑珍; 赵洛沙

    2009-01-01

    目的 观察小剂量替米沙坦与雷米普利联用对慢性心力衰竭(CHF)患者心功能及血浆肾素-血管紧张素Ⅱ-醛固酮系统(BASS)、脑钠素(BNP)的影响.方法 100例慢性心力衰竭患者随机分为A、B、C 3组,在常规治疗的基础上,A组:33例,替米沙坦80mg/d;B组:33例,雷米普利5mg/d;C组:34例,替米沙坦40mg/d+雷米普利2.5mg/d;疗程6个月.治疗前后分别超声测定左室舒张末内径(LVEDD)、左室射血分数(LVEF),测定血浆肾素活性(Ben)、血管紧张素Ⅱ(Ang Ⅱ)、醛固酮(Ald)及BNP水平.结果 3组患者治疗6个月后,LVEDD、LVEF均有明显改善,与治疗前相比差异有统计学意义(P0.05).各组治疗后Ald、BNP水平均明显降低,与治疗前相比有统计学差异(P 0.01). The concentration of Ald and BNP was decreased in all groups (P < 0.01). Ald and BNP were decreased more significantly in C group than those in A group or B group. Conclusion Combination of low dose of telmisartan and ramipril therapy has more benificial clinical features than telmisartan or ramipril alone in patients with CHF.

  8. Updates on the treatment of essential hypertension: a summary of AHRQ's comparative effectiveness review of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and direct renin inhibitors.

    Science.gov (United States)

    Powers, Benjamin; Greene, Laurence; Balfe, Lisa M

    2011-10-01

    In 2007, the Agency for Healthcare Research and Quality (AHRQ) published a comparative effectiveness review (CER) on the benefits and risks of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) for treating essential hypertension in adults. The main findings indicated that the 2 classes of antihypertensive medications caused similar reductions in blood pressure, although higher rates of adverse events, especially cough, were reported by patients treated with ACEIs. In addition, the 2007 review indicated no treatment related differences in lipid levels, glycemic control, or progression of kidney disease among the agents. Since 2007, 39 relevant studies have been published that compare outcomes for adults treated with ACEIs versus ARBs or a drug in one of these 2 classes versus a direct renin inhibitor (DRI). To systematically analyze findings from the new research, AHRQ commissioned and, in June 2011, published an updated comparative effectiveness review on the benefits and risks of agents that target the renin-angiotensin- aldosterone system (RAAS), specifically ACEIs, ARBs, and DRIs. To (a) familiarize health care professionals with the methods and findings from AHRQ's 2011 comparative effectiveness review on ACEIs, ARBs, and DRIs for adults with essential hypertension; (b) provide commentary and encourage consideration of the clinical and managed care applications of the review findings; and (c) identify limitations to the existing research on the benefits and risks of ACEIs, ARBs, and DRIs. Consistent with the findings from AHRQ's 2007 report, the 2011 update indicated no overall differences in blood pressure control, mortality rates, and major cardiovascular events in patients treated with ACEIs versus ARBs. With a low strength of evidence, 2 studies reported a small significantly greater blood pressure reduction for patients treated with the DRI aliskiren versus the ACEI ramipril. Studies evaluating the DRI aliskiren

  9. [Thyroid and cardiovascular system].

    Science.gov (United States)

    Gallowitsch, Hans-Jürgen

    2005-10-01

    The cardiocirculatory changes in hyperthyroidism seem to be an accommodation to the increased metabolic demands and lead to an increased perfusion of the peripheral tissues. Due to the influence of elevated thyroid hormone levels, contractility, stroke volume, resting heart rate, and contraction and relaxation velocity of the left ventricle increase. Caused by direct effect on the smooth vascular muscle, systemic vascular resistance is decreased with the consequence of a diminished afterload and an increased cardiac efficiency. The activation of the renin-angiotensin-aldosteron system and the increased production of erythropoietin additionally lead to an increased blood volume, which increases cardiac preload together with the increased venous backflow. Manifest hypothyroidism is characterized by bradycardia and diastolic dysfunction in rest and systolic dysfunction at stress. Despite a slight increase of diastolic blood pressure due to an increased systemic vascular resistance, blood pressure remains nearly stable because of diminished cardiac output. Hypercholesterinaemia and diastolic hypertension in hypothyroid patients can lead to the development of arteriosclerosis and coronary heart disease (CHD). Also subclinical hypothyroidism is associated with a significantly higher risk for arteriosclerosis and CHD, whereas subclinical hyperthyroidism seems to be associated with an increased mortality for all reasons, especially for cardiovascular diseases.

  10. Plant Flavonoids as Angiotensin Converting Enzyme Inhibitors in Regulation of Hypertension

    Directory of Open Access Journals (Sweden)

    H.P. Vasantha Rupasinghe

    2011-05-01

    Full Text Available Background: Angiotensin converting enzyme (ACE is a key component in the renin angiotensin aldosterone system (RAAS which regulates blood pressure. As the over expression of RAAS is associated with vascular hypertension, ACE inhibition has become a major target control for hypertension. The research on potential ACE inhibitors is expanding broadly and most are focused on natural product derivatives such as peptides, polyphenolics, and terpenes. Plant polyphenolics are antioxidant molecules with various beneficial pharmacological properties. The current study is focused on investigating and reviewing the ACE inhibitory property of fruit flavonoids. An apple skin extract (ASE rich in flavonoids, the major constituents of the extract and their selected metabolites were assessed for the ACE inhibitory property in vitro. It is important to investigate the metabolites along with the flavonoids as they are the constituents active inside the human body.Objective: To investigate whether flavonoids, flavonoid rich apple extracts and their metabolites could inhibit ACE in vitro.Method: The samples were incubated with sodium borate buffer (30 μL, pH 8.3, 150 μL of substrate (Hip-His-Liu and ACE (30 μL at 37 oC for 1 h. The reaction was stopped by addition of 150 μL of 0.3M NaOH. The enzyme cleaved substrate was detected by making a fluorimetricadduct by adding 100 μL of o-phthaladehyde for 10 min at room temperature. Reaction wasstopped by adding 50 μL of 3M HCl. Fluorescence was measured by using a FluoStar Optimaplate reader at excitation of 350 nm and emission of 500 nm.Results: The extract and the compounds showed a concentration dependant enzyme inhibition.Increasing concentrations from 0.001 ppm to 100 ppm of ASE showed an increment of 29% to64% ACE inhibition. The IC50 (concentration of test compound which gives 50% enzymeinhibition values of ASE, quercetin, quercetin-3-glucoside, quercetin-3-galactoside, cyanidin-3-galactoside were 49

  11. Magnetic resonance imaging left ventricular mass reduction with fixed-dose angiotensin-converting enzyme inhibitor-based regimens in patients with high-risk hypertension.

    Science.gov (United States)

    Reichek, Nathaniel; Devereux, Richard B; Rocha, Ricardo A; Hilkert, Robert; Hall, Donna; Purkayastha, Das; Pitt, Bertram

    2009-10-01

    Left ventricular hypertrophy, a major cardiovascular risk factor for morbidity and mortality, is commonly caused by arterial hypertension. The renin-angiotensin-aldosterone system may contribute to the pathogenesis of left ventricular hypertrophy. The Assessment of Lotrel in Left Ventricular Hypertrophy and Hypertension Study compared a single-pill combination of amlodipine/benazepril at doses 5.0/20.0 mg, 5.0/40.0 mg, and 10.0/40.0 mg with hydrochlorothiazide/benazepril at doses 12.5/20.0 mg, 12.5/40.0 mg, and 25.0/40.0 mg on the reduction of left ventricular mass index measured by cardiac MRI in stage 2 hypertensive patients over 52 weeks of treatment in a randomized clinical trial. A total of 125 male and female patients, > or =55 years of age, with echocardiographic left ventricular hypertrophy and high-risk hypertension defined as blood pressure > or =160/100 mm Hg or current antihypertensive treatment were enrolled. After 52 weeks of treatment, left ventricular mass index was significantly reduced from baseline with amlodipine/benazepril (mean: 10.16 g/m(2)) or hydrochlorothiazide/benazepril (mean: 6.74 g/m(2); both Pamlodipine/benazepril (P=0.02). Both treatments were well tolerated.

  12. Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors

    Directory of Open Access Journals (Sweden)

    Eduardo Pimenta

    2009-05-01

    Full Text Available Eduardo Pimenta1, Suzanne Oparil21Endocrine Hypertension Research Center and Clinical Center of Research Excellence in Cardiovascular Disease and Metabolic Disorders, University of Queensland School of Medicine, Princess Alexandra Hospital, Brisbane, QLD, Australia; 2Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, USAbstract: The renin-angiotensin-aldosterone system (RAAS is an important mediator of blood pressure (BP and volume regulation in both normotensive and hypertensive persons and is a major contributor to hypertension-related target organ damage. The concept of renin inhibition for managing hypertension by blocking the RAAS pathway at its point of activation is very attractive since the renin-angiotensinogen reaction is the first and rate-limiting step in the generation of angiotensin II (Ang II. Aliskiren, the first in a new class of orally effective direct renin inhibitors (DRIs, is approved for the treatment of hypertension. It is effective in reducing BP in the general population of hypertensive patients and in special patient groups such as obese persons, and has a tolerability and safety profile similar to placebo. Aliskiren has renoprotective, cardioprotective and anti-atherosclerotic effects in animal models that appear to be independent of BP lowering. It reduces proteinuria in diabetic patients and has favorable neurohumoral effects in patients with symptomatic heart failure. Additional outcome trials are needed to establish the role of this novel class of antihypertensive medication in the therapeutic armamentarium.Keywords: hypertension, renin inhibitors, renin-angiotensin-aldosterone system

  13. Management of Hyperkalemia: An Update for the Internist.

    Science.gov (United States)

    Kovesdy, Csaba P

    2015-12-01

    Hyperkalemia is a clinically important electrolyte abnormality that occurs most commonly in patients with chronic kidney disease. Due to its propensity to induce electrophysiological disturbances, severe hyperkalemia is considered a medical emergency. The management of acute and chronic hyperkalemia can be achieved through the implementation of various interventions, one of which is the elimination of medications that can raise serum potassium levels. Because many such medications (especially inhibitors of the renin-angiotensin aldosterone system) have shown beneficial effects in patients with cardiovascular and renal disease, their discontinuation for reasons of hyperkalemia represent an undesirable clinical compromise. The emergence of 2 new potassium-binding medications for acute and chronic therapy of hyperkalemia may soon allow the continued use of medications such as renin-angiotensin-aldosterone system inhibitors even in patients who are prone to hyperkalemia. This review article provides an overview of the physiology and the pathophysiology of potassium metabolism and hyperkalemia, the epidemiology of hyperkalemia, and its acute and chronic management. We discuss in detail emerging data about new potassium-lowering therapies, and their potential future role in clinical practice.

  14. Blockade of the renin-angiotensin system in small arteries and anticontractile function of perivascular adipose tissue.

    Science.gov (United States)

    Rosei, Claudia Agabiti; Withers, Sarah B; Belcaid, Laila; De Ciuceis, Carolina; Rizzoni, Damiano; Heagerty, Anthony M

    2015-05-01

    In patients with obesity, there is increased inflammation with attendant oxidative stress in perivascular adipose tissue. This has functional consequences with loss of vasodilator adipokine bioavailability. Part of the inflammatory response is mediated by increased activation of the renin-angiotensin-aldosterone axis. Therefore, this study was designed to investigate whether angiotensin-converting enzyme inhibitors or angiotensin receptor blockers can improve the anticontractile function of perivascular adipose tissue. Segments of rat mesenteric small artery were dissected and mounted in a wire myograph and contracted to incremental doses of norepinephrine in the presence and absence of perivascular adipose tissue and in conditions of normal oxygenation or after hypoxia and incubated with captopril or telmisartan. Vessels with perivascular adipose tissue contracted significantly less than arteries with perivascular adipose tissue removed under normal oxygenation conditions, indicating that perivascular adipose tissue exerts an anticontractile effect. Hypoxia induced a loss of this anticontractile effect which could be completely prevented with captopril or telmisartan. The in-vitro creation of a hypoxic environment can simulate the loss of anticontractile perivascular adipose tissue function seen in vivo in obese patients, and this can be prevented using inhibitors of the renin-angiotensin cascade.

  15. Hypertension and hemodialysis: pathophysiology and outcomes in adult and pediatric populations.

    Science.gov (United States)

    Van Buren, Peter N; Inrig, Jula K

    2012-03-01

    Hypertension is prevalent in adult and pediatric end-stage renal disease patients on hemodialysis. Volume overload is a primary factor contributing to hypertension, and attaining true dry weight remains a priority for nephrologists. Other contributing factors to hypertension include activation of the sympathetic and renin-angiotensin-aldosterone systems, endothelial cell dysfunction, arterial stiffness, exposure to hypertensinogenic drugs, and electrolyte imbalances during hemodialysis. Epidemiologic studies in adults show that uncontrolled hypertension results in cardiovascular morbidity, but reveal increased mortality risk at low blood pressure, so that it remains unclear what the target blood pressure should be. Despite the lack of a definitive BP target, gradual dry weight reduction should be the first intervention for BP control. Renin-angiotensin-aldosterone system inhibitors have been shown to improve cardiovascular morbidity and mortality and are recommended as the initial pharmacologic therapy for hypertensive hemodialysis patients. Short-daily or nocturnal hemodialysis are also good therapeutic options for these patients. It is already established that hypertension in pediatric hemodialysis patients is associated with adverse cardiovascular outcomes, and there is emerging evidence that the mechanisms causing hypertension are similar to adults. Hypertension in adult and pediatric hemodialysis patients warrants aggressive management, although clinical trial evidence of a target BP that improves mortality does not currently exist.

  16. Vitamin D and the cardiovascular system.

    Science.gov (United States)

    Beveridge, L A; Witham, M D

    2013-08-01

    Vitamin D, a secosteroid hormone, affects multiple biological pathways via both genomic and nongenomic signalling. Several pathways have potential benefit to cardiovascular health, including effects on parathyroid hormone, the renin-angiotensin-aldosterone system, vascular endothelial growth factor and cytokine production, as well as direct effects on endothelial cell function and myocyte calcium influx. Observational data supports a link between low vitamin D metabolite levels and cardiovascular health. Cross-sectional data shows associations between low 25-hydroxyvitamin D levels and stroke, myocardial infarction, diabetes mellitus, hypertension, and heart failure. Longitudinal data also suggests a relationship with incident hypertension and new cardiovascular events. However, these associations are potentially confounded by reverse causality and by the effects that other cardiovascular risk factors have on vitamin D metabolite levels. Intervention studies to date suggest a modest antihypertensive effect of vitamin D, no effect on serum lipids, a small positive effect on insulin resistance and fasting glucose, and equivocal actions on arterial stiffness and endothelial function. Analysis of cardiovascular event data collected from osteoporosis trials does not currently show a clear signal for reduced cardiovascular events with vitamin D supplementation, but results may be confounded by the coadministration of calcium, and by the secondary nature of the analyses. Despite mechanistic and observational data that suggest a protective role for vitamin D in cardiovascular disease, intervention studies to date are less promising. Large trials using cardiovascular events as a primary outcome are needed before vitamin D can be recommended as a therapy for cardiovascular disease.

  17. Type 2 diabetes mellitus and hypertension: an update.

    Science.gov (United States)

    Lastra, Guido; Syed, Sofia; Kurukulasuriya, L Romayne; Manrique, Camila; Sowers, James R

    2014-03-01

    Patients with hypertension and type 2 diabetes are at increased risk of cardiovascular and chronic renal disease. Factors involved in the pathogenesis of both hypertension and type 2 diabetes include inappropriate activation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, impaired insulin-mediated vasodilatation, augmented sympathetic nervous system activation, altered innate and adaptive immunity, and abnormal sodium processing by the kidney. The renin-angiotensin-aldosterone system blockade is a key therapeutic strategy in the treatment of hypertension in type 2 diabetes. Emerging therapies for resistant hypertension as often exists in patients with diabetes, include renal denervation and carotid body denervation. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. The Effect of Moderate Hypothermia on Renin-Angiotensin – Aldosterone System in Male Rats

    Directory of Open Access Journals (Sweden)

    M. Kourosh Arami

    2004-04-01

    Full Text Available Hypothermia in nature occurs in hibernating animals. It has applications in medicine in open heart surgery,organ and connective tissue preserving, altitude medicine and geriatrics. Despite the vastness of studies on hypothermia many of its biologic and physiologic effects including endocrine system alterations are still poorly recognized. In this study the effect of hypothermia on renin- angiotensin-aldosterone axis was explored. Ten male wistar albino rats (mean age 5 months were anesthetized by intraperitoneal injection of chloralhydrat (0.5 m1/100gr body weight. Then animals were placed in hypothermia apparatus . Their body temperature were reduced to 250 C. AngiotensinI(ANGI and aldosterone (ALD levels of serum were measured by radioimmunoassay before and after hypothermia induction and once every 24 hours for three days. Plasma renin activity (PRA was also measured by using the standard formula of angiotensin determinates at two temperatures of 40C and 370C . The results showed that PRA,ANGI and ALD increased significantly immedietly after hypothermia (p<0.03. Later changes were followed as these factors decreased to basal level, except in the case of aldosterone which maintained its increased level significantly for 24 hours (p<0.05. It seems that moderate hypothermia have stimulatory effect on PRA,ANGI and ALD that results of this study confirm it.

  19. 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.

  20. [Vitamin D hormone system and diabetes mellitus: lessons from selective activators of vitamin D receptor and diabetes mellitus].

    Science.gov (United States)

    Jódar-Gimeno, Esteban; Muñoz-Torres, Manuel

    2013-02-01

    The vitamin D hormone system has significant skeletal and extra-skeletal effects. Vitamin D receptor occurs in different tissues, and several cells other than renal cells are able to locally produce active vitamin D, which is responsible for transcriptional control of hundreds of genes related to its pleiotropic effects. There is increasing evidence relating vitamin D to development and course of type 1 and 2 diabetes mellitus. Specifically, influence of vitamin D on the renin-angiotensin-aldosterone system, inflammatory response, and urinary albumin excretion could explain the relevant impact of vitamin D status on diabetic nephropathy. Selective vitamin D receptor activators are molecules able to reproduce agonistic or antagonistic effects of active vitamin D depending on the tissue or even on the cell type. Specifically, paricalcitol has a beneficial profile because of its potency to reduce parathyroid hormone, with lower effects on serum calcium or phosphate levels. Moreover, in patients with diabetes and renal disease, paricalcitol decreases microalbuminuria, hospitalization rates, and cardiovascular mortality. Therefore, these molecules represent an attractive new option to improve prognosis of renal disease in patients with diabetes.

  1. Angiotensin II Type 1 receptor (AGTR1) gene polymorphisms are associated with vascular manifestations in patients with systemic sclerosis (SSc).

    Science.gov (United States)

    Rodríguez-Reyna, Tatiana S; Núñez-Alvarez, Carlos; Cruz-Lagunas, Alfredo; Posadas-Sánchez, Rosalinda; Pérez-Hernández, Nonanzit; Jiménez-Alvarez, Luis; Ramírez-Martínez, Gustavo; Granados, Julio; Vargas-Alarcón, Gilberto; Zúñiga, Joaquín

    2016-07-01

    Systemic sclerosis (SSc) shows variable clinical expression in different ethnic groups; vascular abnormalities are a prominent feature of this disease and its clinical expression may be influenced by genetic factors. Herein, we describe 15 polymorphisms of the renin-angiotensin-aldosterone pathway in 170 Mexican admixed SSc patients (defined as patients with Mexican ancestry for at least 3 generations) and 199 healthy controls. We determined the presence of angiotensin II Type 1 receptor (AGTR1), angiotensin converting enzyme (ACE) and Endothelin 1 single nucleotide polymorphisms (SNPs) using 5' exonuclease TaqMan genotyping assays on a 7900HT real-time fast polymerase chain reaction (PCR) system. These polymorphisms had a similar distribution between SSc patients and controls, but we found that the AGTR1 G-680T (rs275652) (p = 0.02; OR 3.5; 95%CI 1.2-10.4) and AGTR1 A-119G (rs275653) (p = 0.008; OR 4.2; 95% CI 1.5-12.1) polymorphisms were associated with severe vascular involvement in our SSc patients. This is the first report of the association of these polymorphisms with vasculopathy in Mexican admixed SSc patients. Our findings suggested that the angiotensin II Type 1 receptor genotype may influence the clinical expression of vasculopathy in these patients. Functional analyses should follow. © The Author(s) 2016.

  2. CHRONIC KIDNEY DISEASE RAAS blockade and diastolic heart failure in chronic kidney disease

    NARCIS (Netherlands)

    Franssen, Casper F. M.; Navis, Gerjan

    New data from Ahmed et al. show that discharge prescriptions for renin-angiotensin-aldosterone inhibitor therapy are associated with a significant reduction in all-cause mortality in elderly patients with diastolic heart failure and chronic kidney disease (CKD). These observational data support the

  3. Volume control in treatment-resistant congestive heart failure : role for peritoneal dialysis

    NARCIS (Netherlands)

    Broekman, K. E.; Sinkeler, S. J.; Waanders, F.; Bartels, G. L.; Navis, G.; Janssen, W. M. T.

    2014-01-01

    Chronic congestive heart failure (HF) has a rising prevalence and increasing impact on health care systems. Current treatment consists of diuretics, renin-angiotensin-aldosterone system blockers, and restriction of salt and fluids. This strategy is often hampered by a drop in effective circulating v

  4. The emerging role of ACE2 in physiology and disease

    NARCIS (Netherlands)

    Hamming, I.; Cooper, M. E.; Haagmans, B. L.; Hooper, N. M.; Korstanje, R.; Osterhaus, A. D. M. E.; Timens, W.; Turner, A. J.; Navis, G.; van Goor, H.

    The renin-angiotensin-aldosterone system (RAAS) is a key regulator of systemic blood pressure and renal function and a key player in renal and cardiovascular disease. However, its (patho)physiological roles and its architecture are more complex than initially anticipated. Novel RAAS components that

  5. Recurrence of Acute Page Kidney in a Renal Transplant Allograft

    Directory of Open Access Journals (Sweden)

    Rajan Kapoor

    2016-01-01

    Full Text Available Acute Page Kidney (APK phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS. Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft.

  6. Recurrence of Acute Page Kidney in a Renal Transplant Allograft.

    Science.gov (United States)

    Kapoor, Rajan; Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan

    2016-01-01

    Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft.

  7. 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, Anna Titia; Heerspink, H.J.L.; Zuurman, M.; Visser, F.W.; Kocks, Menno; Boomsma, F.; Navis, Ger Jan

    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 effe

  8. Determining the Optimal Protocol for Measuring an Albuminuria Class Transition in Clinical Trials in Diabetic Kidney Disease

    DEFF Research Database (Denmark)

    Kröpelin, Tobias F; de Zeeuw, Dick; Remuzzi, Giuseppe

    2016-01-01

    clinical trials testing the effect of renin-angiotensin-aldosterone system intervention on albuminuria class transition in patients with diabetes: the BENEDICT, the DIRECT, the ALTITUDE, and the IRMA-2 Trial. The definition of albuminuria class transition used in each trial differed from the definitions...

  9. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan

    NARCIS (Netherlands)

    L. Vogt (Liffert); F. Waanders (Femke); F. Boomsma (Frans); D. de Zeeuw (Dick); G. Navis (Gerjan)

    2008-01-01

    textabstractThere is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these

  10. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan

    NARCIS (Netherlands)

    Vogt, Liffert; Waanders, Fernke; Boornsma, Frans; de Zeeuw, Dick; Navis, Gerjan

    2008-01-01

    There is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these intervention

  11. 血管紧张素Ⅱ受体拮抗剂的临床研究现状与展望

    Institute of Scientific and Technical Information of China (English)

    柯道正; 唐海沁

    2002-01-01

    @@ 肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system,RAAS)在血压调节机制中起着极为重要的作用,目前高血压的治疗日益集中在抑制血管紧张素Ⅱ(AngⅡ)水平上.

  12. Recurrence of Acute Page Kidney in a Renal Transplant Allograft

    Science.gov (United States)

    Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan

    2016-01-01

    Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft. PMID:27725836

  13. 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 effe

  14. Fibroblast Growth Factor 23: a Bridge Between Bone Minerals and Renal Volume Handling

    NARCIS (Netherlands)

    Humalda, Jelmer Kor

    2016-01-01

    The work in this thesis addresses the interaction between the phosphate-regulating hormone Fibroblast Growth Factor 23 (FGF-23) as key player in bone-mineral homeostasis and renal volume handling, mainly in the context of the renin-angiotensin-aldosterone system (RAAS). First, we elaborate on the ro

  15. Increased plasma aldosterone during atrial fibrillation declines following cardioversion

    DEFF Research Database (Denmark)

    Soeby-Land, C; Dixen, U; Therkelsen, S K;

    2011-01-01

    The renin-angiotensin-aldosterone system (RAAS) may be activated during atrial fibrillation (AF); our aim was to evaluate the level of aldosterone in patients with either permanent AF, persistent AF scheduled for cardioversion or patients in sinus rhythm (SR). We hypothesized that an increased...... level of aldosterone is found in patients with AF, decreasing in patients with restored SR....

  16. Primate response to angiotensin infusion and high sodium intake differ by sodium lithium countertransport phenotype

    NARCIS (Netherlands)

    Spradling-Reeves, K.D.; Shade, R.E.; Haywood, J.R.; Cox, L.A.E.

    2017-01-01

    An increased level of sodium-lithium countertransport (SLC) activity has been associated with salt-sensitive hypertension. Previous findings have suggested that dysregulation of the renin-angiotensin-aldosterone system (RAAS) may be involved in the mechanism linking elevated SLC activity and hyperte

  17. 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

  18. Worsening renal function and outcome in heart failure patients with reduced and preserved ejection fraction and the impact of angiotensin receptor blocker treatment : data from the CHARM-study programme

    NARCIS (Netherlands)

    Damman, Kevin; Solomon, Scott D.; Pfeffer, Marc A.; Swedberg, Karl; Yusuf, Salim; Young, James B.; Rouleau, Jean L.; Granger, Christopher B.; McMurray, John J. V.

    2016-01-01

    Aims We investigated the association between worsening renal function (WRF) that occurs during renin-angiotensin-aldosterone system inhibition initation and outcome in heart failure (HF) patients with preserved ejection fraction (HFPEF) and compared this with HF patients with reduced ejection fracti

  19. 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

    2014-01-01

    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

  20. Higher filtration fraction in formerly early-onset preeclamptic women without comorbidity

    NARCIS (Netherlands)

    Toering, Tsjitske J.; van der Graaf, Anne Marijn; Visser, Folkert W.; Groen, Henk; Faas, Marijke M.; Navis, Gerjan; Lely, A. Titia

    2015-01-01

    Formerly preeclamptic women have an increased risk for developing end-stage renal disease, which has been attributed to altered renal hemodynamics and abnormalities in the renin-angiotensin-aldosterone system. Whether this is due to preeclampsia itself or to comorbid conditions is unknown. Renal hem

  1. 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 unde

  2. Varying protein source and quantity does not significantly improve weight loss, fat loss, or satiety in reduced energy diets among midlife adults

    Science.gov (United States)

    This pilot study tested whether varying protein source and quantity in a reduced energy diet would result in significant differences in weight, body composition, and renin angiotensin aldosterone system activity in midlife adults. Eighteen subjects enrolled in a 5 month weight reduction study, invol...

  3. Vasoactive substances in the circulatory dysfunction of cirrhosis

    DEFF Research Database (Denmark)

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

    2001-01-01

    and calcitonin gene-related peptide, are among candidates in the vasodilatation and the increased arterial compliance recently described in advanced cirrhosis. Reflex-induced enhanced sympatho-adrenal activity, activation of the renin-angiotensin-aldosterone system, and elevated circulating vasopressin...... function and sodium-water retention as the outcome. These aspects are relevant to therapy....

  4. Urinary renin and angiotensinogen in type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, Frederik; Lu, Xifeng; Rossing, Peter;

    2013-01-01

    Urinary levels of renin-angiotensin-aldosterone system (RAAS) components may reflect renal RAAS activity and/or the renal efficacy of RAAS inhibition. Our aim was to determine whether urinary angiotensinogen and renin are circulating RAAS-independent markers during RAAS blockade....

  5. Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy

    NARCIS (Netherlands)

    Siwy, Justyna; Schanstra, Joost P.; Argiles, Angel; Bakker, Stephan J. L.; Beige, Joachim; Boucek, Petr; Brand, Korbinian; Delles, Christian; Duranton, Flore; Fernandez-Fernandez, Beatriz; Jankowski, Marie-Luise; Al Khatib, Mohammad; Kunt, Thomas; Lajer, Maria; Lichtinghagen, Ralf; Lindhardt, Morten; Maahs, David M.; Mischak, Harald; Mullen, William; Navis, Gerarda; Noutsou, Marina; Ortiz, Alberto; Persson, Frederik; Petrie, John R.; Roob, Johannes M.; Rossing, Peter; Ruggenenti, Piero; Rychlik, Ivan; Serra, Andreas L.; Snell-Bergeon, Janet; Spasovski, Goce; Stojceva-Taneva, Olivera; Trillini, Matias; von der Leyen, Heiko; Winklhofer-Roob, Brigitte M.; Zuerbig, Petra; Jankowski, Joachim

    2014-01-01

    Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system

  6. Prognostic value of renin and prorenin in heart failure patients with decreased kidney function

    NARCIS (Netherlands)

    Szymanski, Mariusz K.; Damman, Kevin; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; Hillege, Hans L.; de Boer, Rudolf A.

    2011-01-01

    Background The renin-angiotensin-aldosterone system (RAAS) plays a key role in the progression of heart failure (HF) and concomitant kidney dysfunction. Despite the use of RAAS blockade, sustained activation of RAAS has been suggested to link with adverse outcome. We aimed to investigate the prognos

  7. Analysis of the Total Surgical Cardiac Denervation by Computer Simulation

    Science.gov (United States)

    2007-11-02

    filtration rate and increase vasopressin, plasma renin activity, angiotensin II and aldosteron” [2][3]. It is claimed that these effects weaken...CE: Chemoreceptor Effect OSR: Autonomous System Resp. CK: Potassium Concent PPC: Plasma Osmotic Pressure CNa: Sodium Concentration RAP: Right...receptors respond to hypervolemia by supressing vasopressin, renin - angiotensin-aldosteron axis, thirst and sympathetic traffic to the kidney

  8. Vitamin D analogues to target residual proteinuria : potential impact on cardiorenal outcomes

    NARCIS (Netherlands)

    Humalda, Jelmer K.; Goldsmith, David J. A.; Thadhani, Ravi; de Borst, Martin H.

    2015-01-01

    Residual proteinuria, the amount of proteinuria that remains during optimally dosed renin-angiotensin-aldosterone system (RAAS) blockade, is an independent risk factor for progressive renal function loss and cardiovascular complications in chronic kidney disease (CKD) patients. Dual RAAS blockade ma

  9. Pretreatment renal vascular tone predicts the effect of specific renin inhibition on natriuresis in essential hypertension

    NARCIS (Netherlands)

    van Paassen, P; Navis, GJ; de Jong, PE; de Zeeuw, D

    1999-01-01

    Background In essential hypertension an elevated renal vascular resistance (RVR) may be a marker of renin-angiotensin-aldosterone system-mediated impairment of renal sodium excretion. This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic respon

  10. 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.

    2013-01-01

    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

  11. 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 v

  12. Vitamin D analogues to target residual proteinuria : potential impact on cardiorenal outcomes

    NARCIS (Netherlands)

    Humalda, Jelmer K.; Goldsmith, David J. A.; Thadhani, Ravi; de Borst, Martin H.

    2015-01-01

    Residual proteinuria, the amount of proteinuria that remains during optimally dosed renin-angiotensin-aldosterone system (RAAS) blockade, is an independent risk factor for progressive renal function loss and cardiovascular complications in chronic kidney disease (CKD) patients. Dual RAAS blockade ma

  13. 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...

  14. 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

  15. SNPs in MicroRNA Binding Sites in 3′-UTRs of RAAS Genes Influence Arterial Blood Pressure and Risk of Myocardial Infarction

    NARCIS (Netherlands)

    Nossent, A.Yael; Hansen, Jakob L.; Doggen, Carine; Quax, Paul H.A.; Sheikh, Soren P.; Rosendaal, Frits R.

    2011-01-01

    Background 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. Methods Using online databases dbSNP and TargetScan, we ident

  16. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan

    NARCIS (Netherlands)

    L. Vogt (Liffert); F. Waanders (Femke); F. Boomsma (Frans); D. de Zeeuw (Dick); G. Navis (Gerjan)

    2008-01-01

    textabstractThere is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these

  17. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan

    NARCIS (Netherlands)

    Vogt, Liffert; Waanders, Fernke; Boornsma, Frans; de Zeeuw, Dick; Navis, Gerjan

    There is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these

  18. Aldosterone response to angiotensin II during hypoxemia

    Energy Technology Data Exchange (ETDEWEB)

    Colice, G.L.; Ramirez, G.

    1986-07-01

    Exercise stimulates the renin-angiotensin-aldosterone system (RAAS). However, increases in plasma aldosterone concentrations (PAC) are suppressed when exercise is performed at high altitude or under hypoxemic conditions. As the angiotensin-II response to high-altitude exercise is normal, it is speculated that an inhibitor, discharged during hypoxemia, acted to suppress angiotensin-II-mediated aldosterone release. A study was conducted to test this hypothesis, taking into account the measurement of the aldosterone response to exogenous angiotensin II during normoxemia and hypoxemia. It was found that the dose-response curve of PAC to angiotensin II was not significantly inhibited by the considered model of hypoxemia. The hypoxemia-mediated release of an angiotensin II inhibitor does, therefore, not explain the previous observations of PAC suppression during hypoxemic exercise. 28 references.

  19. Aliskiren and valsartan combination therapy for the management of hypertension

    Directory of Open Access Journals (Sweden)

    Benjamin J Epstein

    2010-08-01

    Full Text Available Benjamin J EpsteinDepartments of Pharmacotherapy and Translational Research and Medicine, Colleges of Pharmacy and Medicine, University of Florida, Gainesville, Florida, USA and East Coast Institute for Research, Jacksonville, Florida, USAAbstract: Combination therapy is necessary for most patients with hypertension, and agents that inhibit the renin-angiotensin-aldosterone system (RAAS are mainstays in hypertension management, especially for patients at high cardiovascular and renal risk. Single blockade of the RAAS with an angiotensin-converting enzyme (ACE inhibitor or angiotensin receptor blocker (ARB confers some cardiorenal protection; however, these agents do not extinguish the RAAS as evidenced by a reactive increase in plasma renin activity (PRA, a cardiovascular risk marker, and incomplete cardiorenal protection. Dual blockade with an ACE inhibitor and an ARB offers no additional benefit in patients with hypertension and normal renal and left ventricular function. Indeed, PRA increases synergistically with dual blockade. Aliskiren, the first direct renin inhibitor (DRI to become available has provided an opportunity to study the merit of DRI/ARB combination treatment. By blocking the first and rate-limiting step in the RAAS, aliskiren reduces PRA by at least 70% and buffers the compensatory increase in PRA observed with ACE inhibitors and ARBs. The combination of a DRI and an ARB or an ACE inhibitor is an effective approach for lowering blood pressure; available data indicate that such combinations favorably affect proteinuria, left ventricular mass index, and brain natriuretic peptide in patients with albuminuria, left ventricular hypertrophy, and heart failure, respectively. Ongoing outcome studies will clarify the role of aliskiren and aliskiren-based combination RAAS blockade in patients with hypertension and those at high cardiorenal risk.Keywords: aliskiren, valsartan, single-pill combination, hypertension, renin-angiotensin-aldosterone

  20. Effects of Statins on Cardiorenal Syndrome

    Directory of Open Access Journals (Sweden)

    Shusuke Yagi

    2012-01-01

    Full Text Available Cardiovascular disease and renal disease have a close relationship that forms a vicious cycle as a cardiorenal syndrome (CRS. Oxidative stress, endothelial dysfunction, and vascular inflammation could be therapeutic targets when the renin-angiotensin-aldosterone system is activated by accumulation of conventional cardiovascular risk factors; however, a strategy for management of CRS has not been established yet. Statins, HMG-CoA reductase inhibitors, have not only cholesterol-lowering effects but also pleiotropic effects on cardiovascular systems, including anti-inflammatory and antioxidant effects and improvement of nitric oxide bioavailability. Since recent studies have indicated that statins have beneficial effects on chronic kidney disease and heart failure as well as coronary artery disease in cholesterol-lowering-dependent/independent manners, treatment with statins might be a successful strategy for preventing deterioration of CRS.

  1. Development of hypertension and effects of benazepril hydrochloride in a canine remnant kidney model of chronic renal failure.

    Science.gov (United States)

    Mishina, Mika; Watanabe, Toshifumi

    2008-05-01

    In order to determine whether hypertension would develop in dogs with chronic renal failure, we performed 7/8 renal ablation in 6 healthy dogs and compared pre- and post-ablation blood pressures determined by telemetry. One month after the renal ablation, blood urea nitrogen and creatinine were significantly increased (pdogs with intact renal function. The dogs with induced renal failure and hypertension were administered an angiotensin-converting enzyme inhibitor, benazepril hydrochloride, once daily for 2 weeks at 2 mg/kg body weight, and changes in blood pressure and the renin-angiotensin-aldosterone (RAA) system were determined. During the administration of benazepril hydrochloride, blood pressure, angiotensin II and aldosterone decreased significantly (pdogs with chronic renal failure through mechanisms involving the RAA system and demonstrate that benazepril hydrochloride improves renal hypertension in dogs.

  2. Short-term mortality risk of serum potassium levels in hypertension

    DEFF Research Database (Denmark)

    Krogager, Maria Lukács; Torp-Pedersen, Christian; Mortensen, Rikke Nørmark;

    2016-01-01

    AIMS: Diuretics and renin-angiotensin-aldosterone system inhibitors are central in the treatment of hypertension, but may cause serum potassium abnormalities. We examined mortality in relation to serum potassium in hypertensive patients. METHODS AND RESULTS: From Danish National Registries, we...... identified 44 799 hypertensive patients, aged 30 years or older, who had a serum potassium measurement within 90 days from diagnosis between 1995 and 2012. All-cause mortality was analysed according to seven predefined potassium levels: 5.......0 mmol/L (hyperkalaemia). Outcome was 90-day mortality, estimated with multivariable Cox proportional hazard model, with the potassium interval of 4.1-4.4 mmol/L as reference. During 90-day follow-up, mortalities in the seven strata were 4.5, 2.7, 1.8, 1.5, 1.7, 2.7, and 3.6%, respectively. Adjusted risk...

  3. Hypertension and atrial fibrillation: epidemiology, pathophysiology and therapeutic implications.

    Science.gov (United States)

    Lau, Y-F; Yiu, K-H; Siu, C-W; Tse, H-F

    2012-10-01

    Hypertension is one of the most important risk factors associated with atrial fibrillation (AF) and increased the risk of cardiovascular events in patients with AF. However, the pathophysiological link between hypertension and AF is unclear. Nevertheless, this can be explained by the hemodynamic changes of the left atrium secondary to long standing hypertension, resulting in elevated left atrium pressure and subsequently left atrial enlargement. Moreover, the activation of renin-angiotensin-aldosterone system (RAAS) activation in patients with hypertension induces left atrial fibrosis and conduction block in the left atrium, resulting in the development of AF. Accordingly, recent studies have shown that effective blockage of RAAS by angiotensin converting enzyme inhibitors or angiotensin receptor antagonist may be effective in both primary and secondary prevention of AF in patients with hypertension, although with controversies. In addition, optimal antithrombotic therapy, blood pressure control as well as rate control for AF are key to the management of patients with AF.

  4. Aliskiren prevents the toxic effects of peritoneal dialysis fluids during chronic dialysis in rats.

    Directory of Open Access Journals (Sweden)

    Juan Pérez-Martínez

    Full Text Available The benefits of long-term peritoneal dialysis (PD in patients with end-stage renal failure are short-lived due to structural and functional changes in the peritoneal membrane. In this report, we provide evidence for the in vitro and in vivo participation of the renin-angiotensin-aldosterone system (RAAS in the signaling pathway leading to peritoneal fibrosis during PD. Exposure to high-glucose PD fluids (PDFs increases damage and fibrosis markers in both isolated rat peritoneal mesothelial cells and in the peritoneum of rats after chronic dialysis. In both cases, the addition of the RAAS inhibitor aliskiren markedly improved damage and fibrosis markers, and prevented functional modifications in the peritoneal transport, as measured by the peritoneal equilibrium test. These data suggest that inhibition of the RAAS may be a novel way to improve the efficacy of PD by preventing inflammation and fibrosis following peritoneal exposure to high-glucose PDFs.

  5. Telmisartan and cardioprotection

    Science.gov (United States)

    Akhrass, Philippe R; McFarlane, Samy I

    2011-01-01

    Cardiovascular risk reduction has been the target of several large clinical trials in the last decade. As the activation of the renin-angiotensin-aldosterone system (RAAS) plays a central role in the pathogenesis of atherosclerosis and cardiovascular disease, RAAS blockade has been suggested to be among the most efficient cardioprotective interventions, as revealed with the angiotensin converting enzyme (ACE) inhibitors trials. The angiotensin receptor blockers’ (ARBs) efficacy in lowering blood pressure has been very well established. Telmisartan is however the first ARB to show a promising role in reducing cardiovascular risk in high-risk patients. This article will highlight the role of telmisartan in cardioprotection, underlying specifically the results of two major randomized controlled trials: ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomized AssessmeNt Study in aCE-iNtolerant subjects with cardiovascular Disease). PMID:22140319

  6. Current and Future Treatment of Hypertension in the SPRINT Era.

    Science.gov (United States)

    Phillips, Robert A

    2015-01-01

    Based on the SPRINT trial, it is highly likely that new SPRINT-era guidelines will establish a blood pressure (BP) goal of SPRINT demonstrated that assignment to an intensive-treatment systolic BP (SBP) goal of SPRINT-era guidelines in the elderly, African Americans, and patients with uncomplicated essential hypertension, diabetes, chronic kidney disease, cardiovascular disease, and coronary artery disease. Specific attention is paid to BP goals and preferred pharmacological antihypertensive therapy in these populations, and an algorithm that incorporates the SPRINT trial results is presented. Inhibitors of the renin-angiotensin-aldosterone system as well as calcium channel blockers are universally accepted as first-line therapy in uncomplicated hypertension, but controversy exists over the role of thiazide diuretics and beta blockers. This review also discusses a physiologically and outcomes-based approach to combination therapy for treatment of hypertension.

  7. Evaluation and Management of Proteinuria After Kidney Transplantation.

    Science.gov (United States)

    Tsampalieros, Anne; Knoll, Greg A

    2015-10-01

    Proteinuria occurs commonly after kidney transplantation. Because there are no specific guidelines for defining and detecting proteinuria in transplant recipients, its prevalence can vary depending on the methods used. Most often, the same cutoffs for defining proteinuria in the nontransplant population are applied. There are several risk factors for proteinuria, including some transplant-specific diagnoses and immunosuppressive medications. Posttransplantation proteinuria is associated with reduced graft survival as well as an increased risk of cardiovascular events and death. Treatments to decrease proteinuria have been based on blocking the renin-angiotensin-aldosterone system with the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. This review describes the measurement, prevalence, etiology, prognostic significance, and management of proteinuria in both adult and pediatric transplant recipients.

  8. Monitoring and managing urinary albumin excretion: practical advice for primary care clinicians.

    Science.gov (United States)

    Bakris, George L; Kuritzky, Louis

    2009-07-01

    Albuminuria has a strong, continuous, direct, linear relationship with adverse cardiovascular (CV) outcomes and chronic kidney disease progression. Even at levels below the accepted upper limit of what is considered "normal" daily albumin excretion (albumin excretion level and adverse CV events is evident. Primary care clinicians (eg, physicians, nurse practitioners, physicians' assistants) are usually the first point of contact for patients at risk for CV and kidney disease. Hence, identifying and treating problematic albuminuria levels are important in primary care. Both the American Diabetes Association (ADA) and the National Kidney Foundation (NKF) endorse routine annual screening for microalbuminuria (small amounts of albumin in the urine). Once excess albumin excretion is detected, clinicians must employ aggressive CV risk reduction. To optimize outcomes, treatment of microalbuminuria often requires the combined skills of experts in primary care, cardiology, metabolic disease, and nephrology. Although blood pressure reduction usually improves microalbuminuria, agents that block the renin-angiotensin-aldosterone system (RAAS) are most efficacious. Renin-angiotensin-aldosterone system blockers (ie, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, direct renin inhibitors) may confer CV and kidney advantages in high-risk patients. Their effects on microalbuminuria reduction are greater than those associated with attaining guideline-recommended blood pressure goals. Effective RAAS blockade sometimes induces transient changes in creatinine and potassium, which merit consistent monitoring for the first 2 to 3 months of their use, but rarely necessitate discontinuation. This article also presents an approach to managing increases in creatinine and potassium that should fit comfortably in the hands of primary care clinicians.

  9. Interaction of the endocrine system with inflammation: a function of energy and volume regulation

    Science.gov (United States)

    2014-01-01

    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

  10. 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

  11. Effects of mildly increasing dialysis sodium removal on renin and sympathetic system in hemodialysis patients

    Institute of Scientific and Technical Information of China (English)

    Shen Yang; Sun Fang; Liu Jing; Ma Lijie; Huang Jing; Zhou Yilun; Liu Wenhu

    2014-01-01

    Background It has been argued that the benefits of reducing sodium loading may be offset by increased activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system.This study aimed to investigate the long-term effects of an increase in dialysis sodium removal on circulating RAAS and sympathetic system in hypertensive hemodialysis (HD) patients with "normal" post-HD volume status.Methods Thirty hypertensive HD patients were enrolled in this pilot trial.After one month period of dialysis with standard dialysate sodium of 138 mmol/L,the patients were followed up for a four months period with dialysate sodium set at 136 mmol/L,without changes in instructions regarding dietary sodium control.During the period of study,the dry weight was adjusted monthly under the guidance of bioimpedance spectroscopy to maintain post-HD volume status in a steady state; 44-hour ambulatory blood pressure,plasma renin,angiotensin Ⅱ (Ang Ⅱ),aldosterone,and norepinephrine (NE) were measured.Results After four months of HD with low dialysate sodium of 136 mmol/L,44-hour systolic and diastolic blood pressures (BPs) were significantly lower (-10 and-6 mmHg),in the absence of changes in antihypertensive medications.No significant changes were observed in plasma renin,Ang Ⅱ,aldosterone,and NE concentrations.The post-HD volume parameters were kept constant.Conclusion Mildly increasing dialysis sodium removal over 4 months can significantly improve BP control and does not activate circulating RAAS and sympathetic nervous system in hypertensive HD patients.

  12. Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications.

    Science.gov (United States)

    Kalil, Graziela Z; Haynes, William G

    2012-01-01

    Obesity markedly increases the risk of hypertension and cardiovascular disease, which may be related to activation of the sympathetic nervous system (SNS). Sympathetic overactivity directly and indirectly contributes to blood pressure (BP) elevation in obesity, including stimulation of the renin-angiotensin-aldosterone system (RAAS). The adipocyte-derived peptide leptin suppresses appetite, increases thermogenesis, but also raises SNS activity and BP. Obese individuals exhibit hyperleptinemia but are resistant to its appetite-suppressing actions. Interestingly, animal models of obesity exhibit preserved sympathoexcitatory and pressor actions of leptin, despite resistance to its anorexic and metabolic actions, suggesting selective leptin resistance. Disturbance of intracellular signaling at specific hypothalamic neural networks appears to underlie selective leptin resistance. Delineation of these pathways should lead to novel approaches to treatment. In the meantime, treatment of obesity-hypertension has relied on antihypertensive drugs. Although sympathetic blockade is mechanistically attractive in obesity-hypertension, in practice its effects are disappointing because of adverse metabolic effects and inferior outcomes. On the basis of subgroup analyses of obese patients in large randomized clinical trials, drugs such as diuretics and RAAS blockers appear superior in preventing cardiovascular events in obesity--hypertension. An underused alternative approach to obesity-hypertension is induction of weight loss, which reduces circulating leptin and insulin, partially reverses resistance to these hormones, decreases sympathetic activation and improves BP and other risk factors. Though weight loss induced by lifestyle is often modest and transient, carefully selected pharmacological weight loss therapies can produce substantial and sustained antihypertensive effects additive to lifestyle interventions.

  13. Salt reduction and hypertension in China: a concise state-of-the-art review

    OpenAIRE

    Liu, Yue; Li, Huiyan; Hong, Siting; Yin, Xinhua

    2015-01-01

    Hypertension (HTN) and its cardiovascular complications such as stroke and heart failure are a serious public health problem around the world. A growing number of studies confirm that salt plays an important role in the development of HTN. Increasing intake of salt leads to abnormal transport of sodium ions at the cellular level with activation of the sympathetic nervous system and renin-angiotensin-aldosterone system. Studies have shown that salt restriction can reduce blood pressure (BP) in...

  14. Efeitos da angiotensina II no sistema cardiovascular

    OpenAIRE

    Trapp, S. M.; Vailati, M. C. F.; Matsubara,Beatriz Bojikian; Schwartz,D.S.

    2009-01-01

    Angiotensin is an important peptide of renin-angiotensin-aldosterone system. This peptide has an important function on arterial blood pressure regulation and body fluid homeostasis. However, its action on abnormal conditions causes deleterious effects on the cardiovascular system. Vascular resistance, hypertension, vascular and myocytes hipertrophy, production of free radicals and pro-inflammatory substances are some of the actions of angiotensin II that can result on cardiovascular remodelin...

  15. [Pathophysiology of hypertension in chronic kidney disease].

    Science.gov (United States)

    Sawicka, Magdalena; Jędras, Mirosław

    2014-01-01

    Hypertension is both an important cause and consequence of chronic kidney disease (CKD). It is present in 80-85% of the patients. The article summarizes the main pathogenetic factors of hypertension in CKD such as: sodium retention, increased activity the renin-angiotensin-aldosterone system and sympathetic nervous system, impaired nitric oxide synthesis and endothelium-mediated vasodilatation, oxidative stress, disorders of calcium metabolism and parathyroid hormone secretion, vascular calcification and increased arterial stiffness.

  16. Obesity-related hypertension: epidemiology, pathophysiology, treatments, and the contribution of perivascular adipose tissue.

    Science.gov (United States)

    Aghamohammadzadeh, Reza; Heagerty, Anthony M

    2012-06-01

    The advent of the obesity epidemic has highlighted the need to re-assess more closely the pathophysiology of obesity-related hypertension with the aim of identifying new therapies. In this article, we review the role of the renin-angiotensin-aldosterone system, sympathetic nervous system, and inflammation in relation to the pathophysiology of this condition. We also discuss the potential role of the perivascular adipose tissue in the context of obesity-related hypertension.

  17. [Effect of combined treatment with dopamine receptor agonists and antagonists of aldosterone on the performance of daily blood pressure monitoring in patients with hypertension and concomitant obesity].

    Science.gov (United States)

    Lyzogub, V G; Sobol', V O; Dolynna, O V; Kuz'mins'ka, L A

    2012-01-01

    In hypertensive patients with concomitant obesity observed decrease in activity of dopaminergic system in conjunction with increased activity of the renin-angiotensin-aldosterone system. Identified changes point to the advisability of appointing this group of patients the dopamine receptor agonist - bromocriptine-KV and antagonist of aldosterone - veroshpiron. As a result of treatment was an increase in dopamine levels in the urine, a decrease of aldosterone in the blood, normalization of the daily blood pressure monitoring.

  18. Direct Activation of ENaC by Angiotensin II: Recent Advances and New Insights

    OpenAIRE

    Zaika, Oleg; Mamenko, Mykola; Staruschenko, Alexander; Pochynyuk, Oleh

    2013-01-01

    Angiotensin II (Ang II) is the principal effector of the renin-angiotensin-aldosterone system (RAAS). It initiates myriad processes in multiple organs integrated to increase circulating volume and elevate systemic blood pressure. In the kidney, Ang II stimulates renal tubular water and salt reabsorption causing antinatriuresis and antidiuresis. Activation of RAAS is known to enhance activity of the epithelial Na+ channel (ENaC) in the aldosterone-sensitive distal nephron. In addition to its w...

  19. Plasma volume expansion by albumin in cirrhosis. Relation to blood volume distribution, arterial compliance and severity of disease

    DEFF Research Database (Denmark)

    Brinch, Kim; Bendtsen, Flemming; Becker, Povl Ulrik;

    2003-01-01

    BACKGROUND/AIMS: The aim of the study was to investigate the effect of a standard albumin load on blood volume distribution, arterial compliance, and the renin-angiotensin-aldosterone system in patients with different degrees of cirrhosis. METHODS: 31 patients with cirrhosis (Child classes A/B/C=...... effective arterial blood volume of such patients, which may be important in the prevention of circulatory dysfunction....

  20. A New Look at Electrolyte Transport in the Distal Tubule

    OpenAIRE

    Eladari, Dominique; Chambrey, Régine; Peti-Peterdi, Janos

    2011-01-01

    The distal nephron plays a critical role in the renal control of homeostasis. Until very recently most studies focused on the control of Na+, K+, and water balance by principal cells of the collecting duct and the regulation of solute and water by hormones from the renin-angiotensin-aldosterone system and by antidiuretic hormone. However, recent studies have revealed the unexpected importance of renal intercalated cells, a subtype of cells present in the connecting tubule and collecting ducts...

  1. Effetto del genotipo sulla massa ventricolare sinistra e sugli eventi cardiovascolari nell'ipertensione arteriosa

    OpenAIRE

    Bulla, Emanuela

    2009-01-01

    Background. Left ventricular mass (LVM) is increased in 20-25% of untreated hypertensive patients and influences cardiovascular morbidity and mortality. It is kept under control by mineralocorticoids, angiotensin II, genetic and emodynamics factors. Association of the renin angiotensin aldosterone system (RAA) genes and sodium sensitivity with LVM has been reported by many authors but it remains controversial for the small sample size of the cohorts studied and for the study design (methodolo...

  2. [Hiperkalemia].

    Science.gov (United States)

    Matuszkiewicz-Rowińska, Joanna; Wojtaszek, Ewa

    2013-01-01

    Hyperkalemia is a common and potentially lethal clinical problem. It may be caused by several drugs, especially those which target the renin-angiotensin--aldosterone system, inability of kidney to excrete potassium, a shift of these ions into the extracellular fluid, or a combination of those mechanisms. It can be also spurious, caused by hemolysis after blood drawing. In the article the conditions associated with hyperkalemia, its diagnosis and the management are reviewed.

  3. [Influence of dopamine receptors agonists on clinical and hemodynamic and neurohumoral indicators in hypertensive patients with concomitant obesity].

    Science.gov (United States)

    Lyzogub, V H; Sobol', V O; Moshkovs'ka, Iu O; Bondarchuk, O M

    2014-01-01

    The article analyzes the results of studying the effects of antihypertensive treatment with the use of agonists dopamine receptors on clinical and hemodynamic and neurohumoral indicators in hypertensive patients with concomitant obesity. Special role is given to the patogenetice factor as dopamine and his relationship with the renin - angiotensin.- aldosterone system, endothelial function, which are aimed at the regulation of blood pressure and obesity formation and progression.

  4. Telmisartan and cardioprotection

    OpenAIRE

    McFarlane S

    2011-01-01

    Philippe R Akhrass, Samy I McFarlaneState University of New York, Downstate Medical Center, Brooklyn, NY, USAAbstract: Cardiovascular risk reduction has been the target of several large clinical trials in the last decade. As the activation of the renin-angiotensin-aldosterone system (RAAS) plays a central role in the pathogenesis of atherosclerosis and cardiovascular disease, RAAS blockade has been suggested to be among the most efficient cardioprotective interventions, as revealed with the a...

  5. Adrenomedullin stimulates renin release and renin mRNA in mouse juxtaglomerular granular cells

    DEFF Research Database (Denmark)

    Jensen, B L; Krämer, B K; Kurtz, A

    1997-01-01

    The recently discovered peptide adrenomedullin (AM) alters blood pressure through effects on the resistance vessels. Moreover, AM modifies the secretion of corticotropin and aldosterone and could thereby indirectly influence blood pressure through the renin-angiotensin-aldosterone system. Although...... on juxtaglomerular cells, possibly through increases in cAMP. AM could act as an autocrine/paracrine stimulatory factor in the control of renin secretion and renin gene expression....

  6. Patients with chronic three-vessel disease in a 15-year follow-up study: genetic and non-genetic predictors of survival.

    OpenAIRE

    2014-01-01

    Genetic and non-genetic predictors of 15-year survival in patients with chronic three-vessel disease (3VD) were investigated. Coronary angiography was performed on 810 subjects with symptoms of stable ischemic heart disease in 1998. The patients with 3VD were genotyped for 23 candidate polymorphisms covering the PPAR-RXR pathway, matrix metalloproteinase-2, renin-angiotensin-aldosterone system, endothelin-1, cytokine genes, MTHFR and APO E variants. Fifteen-year survival data were obtained fr...

  7. No significant effect of angiotensin II receptor blockade on intermediate cardiovascular end points in hemodialysis patients

    DEFF Research Database (Denmark)

    Peters, Christian D; Kjaergaard, Krista D; Jensen, Jens D;

    2014-01-01

    Agents blocking the renin-angiotensin-aldosterone system are frequently used in patients with end-stage renal disease, but whether they exert beneficial cardiovascular effects is unclear. Here the long-term effects of the angiotensin II receptor blocker, irbesartan, were studied in hemodialysis...... the study period significantly correlated with changes in both left ventricular mass and arterial stiffness. Thus, significant effects of irbesartan on intermediate cardiovascular end points beyond blood pressure reduction were absent in hemodialysis patients....

  8. Plasma Angiotensin II Levels In Women With Type 2 Diabetes With Or Without Hypertension

    OpenAIRE

    Ariadno, Etra

    2013-01-01

    ABSTRACT Background. Hypertension is a major risk for the development and progressivity complication of macro and microvascular of diabetes mellitus. Renin-angiotensin-aldosteron system (RAAS), insulin resistance, endothelial dysfunction and autonomic nervous dysfunction play an important part in the pathogenesis of hypertension and type 2 diabetes mellitus. In RAAS, increased angiotensin II constricts arterioles, raises total peripheral resistance and blood volume. The rise in intravascular ...

  9. RETRACTED: Bosentan attenuates cardiac fibrosis in diabetic mice without affecting blood glucose.

    Science.gov (United States)

    Yang, Bo; Chen, Yun-Dai; Li, Min; Zhou, Fei-Hu; Xu, Yong; Wang, Guang-Yi; Li, Tian-De; Xing, You-Hong

    2015-12-01

    At the request of the authors, 'Bosentan attenuates cardiac fibrosis in diabetic mice without affecting blood glucose' Journal of Renin-Angiotensin-Aldosterone System, published ahead of print August 15, 2011 as doi: 10.1177/1470320311417274 has been retracted. This is due to mistakes in the published data at Figure 3. For clarification: this problem came to the attention of Bo Yang only after publication in the journal. Bo Yang immediately brought it to the attention of the Journal.

  10. Salt and left ventricular hypertrophy: what are the links?

    Science.gov (United States)

    Langenfeld, M R; Schmieder, R E

    1995-11-01

    Left ventricular hypertrophy is a frequent and prognostically unfavourable finding in patients with essential hypertension and has been found to be a predictor for the development of essential hypertension in normotensive subjects. Among various genetic, haemodynamic and humoral determinants, dietary salt intake has been demonstrated to influence left ventricular mass in hypertensive disease. Several cross-sectional studies have shown a close relation between dietary salt intake and parameters of left ventricular hypertrophy. Moreover, reduction of dietary sodium intake was associated with a decrease of left ventricular mass in a prospective study. The underlying mechanism of how salt intake modulates myocardial structure has not been explained yet. Three possible explanations are discussed: (1) sodium influences left ventricular mass via raised preload, (2) the sympathetic nervous system acts as a mediator, and (3) the renin-angiotensin-aldosterone system is the responsible link. Recent animal experiments and clinical studies suggest that the renin-angiotensin-aldosterone system may mediate both the cardiotrophic and the blood pressure raising effects of salt. However, not all individuals have a similar high susceptibility to blood pressure elevation develop left ventricular hypertrophy when exposed to high salt intake. We suggest that the underlying mechanism is a dysregulation of the renin-angiotensin-aldosterone system. Some individuals may have an impaired downregulation of angiotensin II synthesis when challenged with high salt intake. Accordingly, we found that relatively too high levels of angiotensin II in relation to urinary sodium excretion were associated with left ventricular hypertrophy in these individuals on high salt intake.

  11. Progress of Aldosterone Breakthroughs%醛固酮逃逸的研究进展

    Institute of Scientific and Technical Information of China (English)

    郭建淑

    2011-01-01

    Renin-angiotensin-aldosterone system inhibitors have become leading drugs in the treatment of hypertension and chronic heart failure. Angiotensin-converting-enzyme inhibitors( ACEI) and angiotensin-receptor blockers ( ARB) do not, however, uniformly suppress the renin-angiotensin-aldosterone system. After a period of therapy with ACEI or ARB, plasma aldosterone levels are elevated in some patients. This phenomenon, is known as 'aldosterone escape' or 'aldosterone breakthrough'. The key questions of how breakthrough happens , how often breakthrough occurs and whether breakthrough leads, to worse outcomes have yet to be definitively answered. This review summarizes reported research on the incidence and mechanism of aldosterone breakthrough, we also discuss the difference of aldosterone breakthrough during the treatment with ACEI or ARB.%肾素-血管紧张素-醛固酮系统抑制剂已成为治疗高血压及心力衰竭的主要药物,然而血管紧张素转换酶抑制剂与血管紧张素Ⅱ受体拮抗剂并没有充分的阻断过度激活的肾素-血管紧张素-醛固酮系统.在经过血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体拮抗剂治疗一段时间后,一部分患者血浆醛固酮水平有所升高,即"醛固酮逃逸现象".该现象的发生率及机制,对临床治疗的影响等重要问题一直不完全清楚,现就醛固醛逃逸现象的发生率、机制、在血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂治疗中的区别等在近年的研究进展做一概要的综述.

  12. 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 BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

  13. The circadian organization of the cardiovascular system in health and disease.

    Science.gov (United States)

    Portaluppi, Francesco

    2014-05-01

    In normal conditions, the temporal organization of blood pressure (BP) is mainly controlled by neuroendocrine mechanisms. Above all, the monoaminergic systems (including variations in activity of the autonomous nervous system, and in secretion of biogenic amines) appear to integrate the major driving factors of temporal variability, but evidence is available also for a role of the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, opioid, renin-angiotensin-aldosterone, and endothelial systems, as well as other vasoactive peptides. Many hormones with established actions on the cardiovascular system (arginine vasopressin, vasoactive intestinal peptide, melatonin, somatotropin, insulin, steroids, serotonin, CRF, ACTH, TRH, endogenous opioids, and prostaglandin E2) are also involved in sleep induction or arousal, which in turn affects BP regulation. Hence, physical, mental, and pathological stimuli which may drive activation or inhibition of these neuroendocrine effectors of biological rhythmicity, may also interfere with the temporal BP structure. On the other hand, the immediate adaptation of the exogenous components of BP rhythms to the demands of the environment are modulated by the circadian-time-dependent responsiveness of the biological oscillators and their neuroendocrine effectors. These notions may contribute to a better understanding of the pathophysiology and therapeutics of hypertension, myocardial ischemia and infarction, cardiac arrhythmias and all kind of acute cardiovascular accidents. For instance, the normal temporal balance between external stimuli and neurohumoral influences with endogenous rhythmicity is preserved in uncomplicated, essential hypertension, whereas it is frequently lost in complicated and secondary forms of hypertension where gross alterations are found in the circadian profile of BP. When all the gates of the critical physiologic functions are aligned at the same time, the susceptibility, and thus risk, of adverse

  14. Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril.

    Science.gov (United States)

    Akif, Mohd; Masuyer, Geoffrey; Schwager, Sylva L U; Bhuyan, Bhaskar J; Mugesh, Govindasamy; Isaac, R Elwyn; Sturrock, Edward D; Acharya, K Ravi

    2011-10-01

    Human somatic angiotensin I-converting enzyme (ACE), a zinc-dependent dipeptidyl carboxypeptidase, is central to the regulation of the renin-angiotensin aldosterone system. It is a well-known target for combating hypertension and related cardiovascular diseases. In a recent study by Bhuyan and Mugesh [Org. Biomol. Chem. (2011) 9, 1356-1365], it was shown that the selenium analogues of captopril (a well-known clinical inhibitor of ACE) not only inhibit ACE, but also protect against peroxynitrite-mediated nitration of peptides and proteins. Here, we report the crystal structures of human testis ACE (tACE) and a homologue of ACE, known as AnCE, from Drosophila melanogaster in complex with the most promising selenium analogue of captopril (SeCap) determined at 2.4 and 2.35 Å resolution, respectively. The inhibitor binds at the active site of tACE and AnCE in an analogous fashion to that observed for captopril and provide the first examples of a protein-selenolate interaction. These new structures of tACE-SeCap and AnCE-SeCap inhibitor complexes presented here provide important information for further exploration of zinc coordinating selenium-based ACE inhibitor pharmacophores with significant antioxidant activity. © 2011 The Authors Journal compilation © 2011 FEBS.

  15. Pathogenesis and Novel Treatment from the Mouse Model of Type 2 Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Masako Furukawa

    2013-01-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage kidney disease worldwide. However, current treatments remain suboptimal. Many factors, such as genetic and nongenetic promoters, hypertension, hyperglycemia, the accumulation of advanced glycation end products (AGEs, dyslipidemia, and albuminuria/proteinuria itself, influence the progression of this disease. It is important to determine the molecular mechanisms and treatment of this disease. The development of diabetes results in the formation of AGEs, oxidative stress, and the activation of the renin-angiotensin-aldosterone system (RAAS within the kidney, which promotes progressive inflammation and fibrosis, leading to DN and declining renal function. A number of novel therapies have also been tested in the experimental diabetic model, including exercise, inhibitors of the RAAS (angiotensin type 1 receptor blockers (ARB, angiotensin-converting enzyme (ACE inhibitors, inhibitors of AGE (pyridoxamine, peroxisome proliferator-activated receptor (PPAR γ agonists (pioglitazone, inhibitors of lipid accumulation (statins and eicosapentaenoic acid (EPA, and the vitamin D analogues. This review summarizes the advances in knowledge gained from our studies and therapeutic interventions that may prevent this disease.

  16. Focus on the Novel Cardiovascular Drug LZC696: from Evidence to Clinical Consideration.

    Science.gov (United States)

    Lin, L M; Wu, Y; Wu, M F; Lin, J X

    2016-12-01

    LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is comprised of the angiotensin receptor blocker valsartan and the neprilysin inhibitor pro-drug sacubitril (AHU377). After oral administration, AHU377 is rapidly metabolized to the active neprilysin inhibitor LBQ657. LCZ696 exerts its effects of diuresis, natriuresis, vasodilation and aldosterone secretion inhibition through simultaneous renin-angiotensin-aldosterone system (RAAS) blockade and natriuretic peptides system (NPS) enhancement. Powerful evidence including PARAMETER and PRARDIGM-HF trials have shown that LCZ696 outperforms RAAS inhibition in treating patients with hypertension and heart failure with reduced ejection fraction (HFrEF), and is well tolerated. In addition, accumulating evidence also suggests its potential use in heart failure with preserved ejection fraction (HFpEF), chronic kidney disease (CKD), post-myocardium infarction (post-MI) and stroke. Both the FDA and CHMP have approved LCZ696 for treatment of HFrEF. Despite all this, some special issues (e.g. use in specific subgroups, adverse events, contraindications and cost-effectiveness analysis) should be considered before its implementation in clinical practice.

  17. Suppression of Aldosterone Synthesis and Secretion by Channel Antagonists

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2012-01-01

    Full Text Available Aldosterone, a specific mineralocorticoid receptor (MR agonist and a key player in the development of hypertension, is synthesized as a final product of renin-angiotensin-aldosterone system. Hypertension can be generally treated by negating the effects of angiotensin II through the use of angiotensin-converting enzyme inhibitors (ACE-Is or angiotensin II type 1 receptor antagonists (ARBs. However, the efficacy of angiotensin II blockade by such drugs is sometimes diminished by the so-called “aldosterone breakthrough” effect, by which ACE-Is or ARBs (renin-angiotensin system (RAS inhibitors gradually lose their effectiveness against hypertension due to the overproduction of aldosterone, known as primary aldosteronism. Although MR antagonists are used to antagonize the effects of aldosterone, these drugs may, however, give rise to life-threatening adverse actions, such as hyperkalemia, particularly when used in conjunction with RAS inhibitors. Recently, several groups have reported that some dihydropyridine Ca2+ channel blockers (CCBs have inhibitory actions on aldosterone production in in vitro and in the clinical setting. Therefore, the use of such dihydropyridine CCBs to treat aldosterone-related hypertension may prove beneficial to circumvent such therapeutic problems. In this paper, we discuss the mechanism of action of CCBs on aldosterone production and clinical perspectives for CCB use to inhibit MR activity in hypertensive patients.

  18. Insight into the interactive residues between two domains of human somatic Angiotensin-converting enzyme and Angiotensin II by MM-PBSA calculation and steered molecular dynamics simulation.

    Science.gov (United States)

    Guan, Shan-shan; Han, Wei-wei; Zhang, Hao; Wang, Song; Shan, Ya-ming

    2016-01-01

    Angiotensin-converting enzyme (ACE), a membrane-bound zinc metallopeptidase, catalyzes the formation of Angiotensin-II (AngII) and the deactivation of bradykinin in the renin-angiotensin-aldosterone and kallikrein-kinin systems. As a hydrolysis product of ACE, AngII is regarded as an inhibitor and displays stronger competitive inhibition in the C-domain than the N-domain of ACE. However, the AngII binding differences between the two domains and the mechanisms behind AngII dissociation from the C-domain are rarely explored. In this work, molecular docking, Molecular Mechanics/Poisson-Boltzmann Surface Area calculation, and steered molecular dynamics (SMD) are applied to explore the structures and interactions in the binding or unbinding of AngII with the two domains of human somatic ACE. Calculated free energy values suggest that the C-domain-AngII complex is more stable than the N-domain-AngII complex, consistent with available experimental data. SMD simulation results imply that electrostatic interaction is dominant in the dissociation of AngII from the C-domain. Moreover, Gln106, Asp121, Glu123, and Tyr213 may be the key residues in the unbinding pathway of AngII. The simulation results in our work provide insights into the interactions between the two domains of ACE and its natural peptide inhibitor AngII at a molecular level. Moreover, the results provide theoretical clues for the design of new inhibitors.

  19. Aliskiren ameliorates sympathetic nerve sprouting and suppresses the inducibility of ventricular tachyarrhythmia in postinfarcted rat heart

    Institute of Scientific and Technical Information of China (English)

    JIA Yin-yu; BAO Zhi-wei; WEI Mei-fang; ZHU Jian-hua; GUI Le

    2013-01-01

    Background Aliskiren is an oral renin inhibitor,which inhibits the first rate limiting step in the renin angiotensin aldosterone system.In this study,sympathetic nerve sprouting and the inducibility of ventricular fibrillation after aliskiren treatment in myocardial infarction were investigated.Methods Male Sprague Dawley rats after coronary artery ligation were randomly allocated to four groups:angiotensin converting enzyme inhibitor enalapril,angiotensin receptor blocker valsartan,β adrenergic receptor blocker carvedilol and rennin inhibitor aliskiren treatment for six weeks.Electrophysiological study,histological examination and Western blotting were performed.Results The plasma norepinephrine level and sympathetic nerve innervation significantly increased in treated infarcted rats compared to untreated rats.Aliskiren treatment reduced the sympathetic nerve innervations after myocardial infarction.There is no significant difference in sympathetic nerve innervations after myocardial infarction among the enalapril,valsartan,carvediloand or aliskiren treated groups.Programmed electrical stimulation study showed that inducible ventricular arrhythmia was reduced,ventricular fibrillation threshold was increased and ventricular effective refractory period was prolonged in enalapril,valsartan,carvedilol and aliskiren treated infarcted rats compared to untreated infarcted rats.Cardiomyocytic apoptosis in infarcted region was significantly decreased in enalapril,valsartan,carvedilol and aliskiren treated infarcted rats.Conclusions Aliskiren ameliorated cardiomyocytic apoptosis,attenuated the sympathetic nerve innervations and reduced the vulnerability of ventricular arrhythmias after myocardial infarction.Enalapril,valsartan and carvedilol have similar effects as aliskiren on cardiomyocytic apoptosis,sympathetic nerve innervations and vulnerability of ventricular arrhythmias after myocardial infarction.

  20. ARBs and ACEis together in the treatment of hypertension and its complications? current practical recommendations.

    Science.gov (United States)

    Ruilope, Luis M; Segura, Julian

    2010-11-01

    Arterial hypertension is highly prevalent in the general population. Its contribution to the development and evolution of cardiovascular and renal disease is well recognized. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) have demonstrated favorable effects on cardiovascular and renal prognosis; however, some limitations have been described, for example angiotensin and aldosterone breakthrough. This article describes several therapeutical strategies that can be administered with an ACEi or ARB, such as the direct renin inhibitors or the aldosterone receptor antagonists. The addition of an ACEi to an ARB or vice versa was initially considered as a way of obtaining a stronger suppression of the renin-angiotensin-aldosterone system (RAAS), but recent evidence has shown that the combination of the two classes of drugs does not seem to afford the expected increase in benefit. RAAS suppression with monotherapy is associated with beneficial cardiovascular effects, but has several limitations. Direct renin inhibitors and aldosterone receptor antagonists will increase the benefits of dual blockade. We need randomized trial data supporting reduction of cardiovascular events with an adequate safety profile using combination therapies.

  1. Drug-induced hyperkalemia.

    Science.gov (United States)

    Ben Salem, Chaker; Badreddine, Atef; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2014-09-01

    Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia.

  2. The burden of hyperkalemia in patients with cardiovascular and renal disease.

    Science.gov (United States)

    Dunn, Jeffrey D; Benton, Wade W; Orozco-Torrentera, Ernesto; Adamson, Robert T

    2015-11-01

    Hyperkalemia is a potentially serious condition that can result in life-threatening cardiac arrhythmias and is associated with an increased mortality risk. Patients older than 65 years who have an advanced stage of chronic kidney disease (stage 3 or higher), diabetes, and/or chronic heart failure are at higher risk for hyperkalemia. To reduce disease progression and improve outcomes in these groups of patients, modulation of the renin-angiotensin-aldosterone system (RAAS) is recommended by guidelines. One limiting factor of RAAS inhibitors at proven doses is the increased risk for hyperkalemia associated with their use. Although there are effective therapeutic options for the short-term, acute management of hyperkalemia, the available strategies for chronic control of high potassium levels have limited effectiveness. The management of high potassium in the long term often requires withdrawing or reducing the doses of drugs proven to reduce cardiovascular and renal outcomes (eg, RAAS inhibitors) or implementing excessive and often intolerable dietary restrictions. Furthermore, withholding RAAS inhibitors may lead to incremental healthcare costs associated with poor outcomes, such as end-stage renal disease, hospitalizations due to cardiovascular causes, and cardiovascular mortality. As such, there is an important unmet need for novel therapeutic options for the chronic management of patients at risk for hyperkalemia. Potential therapies in development may change the treatment landscape in the near future.

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

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    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

  4. Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors

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    Eduardo Pimenta

    2009-06-01

    Full Text Available Eduardo Pimenta1, Suzanne Oparil21Endocrine Hypertension Research Centre and Clinical Centre of Research Excellence in Cardiovascular Disease and Metabolic Disorders, University of Queensland School of Medicine, Greenslopes Princess Alexandra Hospitals, Brisbane, QLD, Australia; 2Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, USAAbstract: The renin–angiotensin–aldosterone system (RAAS is a key mediator of blood pressure (BP and volume regulation in both normotensive and hypertensive persons. Stimulation of RAAS also contributes to hypertension-related target organ damage. The renin–angiotensinogen reaction is the first and rate-limiting step in the generation of angiotensin II (Ang II and has been a target of antihypertensive drug development for decades. Aliskiren is the first in a new class of orally effective direct renin inhibitors (DRIs and is approved for the treatment of hypertension in humans. It effectively reduces BP in the general population of hypertensive patients and has a tolerability and safety profile similar to placebo. Aliskiren has favorable effects on vascular inflammation and remodeling, on neurohumoral mediators of various forms of cardiovascular disease, including heart failure, and on proteinuria in diabetic patients. Additional outcome trials are needed to establish the role of this novel class of antihypertensive medication in preventing cardiovascular disease morbidity and mortality.Keywords: hypertension, renin inhibitors, renin-angiotensin-aldosterone system

  5. Pharmacology of heart failure: From basic science to novel therapies.

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    Lother, Achim; Hein, Lutz

    2016-10-01

    Chronic heart failure is one of the leading causes for hospitalization in the United States and Europe, and is accompanied by high mortality. Current pharmacological therapy of chronic heart failure with reduced ejection fraction is largely based on compounds that inhibit the detrimental action of the adrenergic and the renin-angiotensin-aldosterone systems on the heart. More than one decade after spironolactone, two novel therapeutic principles have been added to the very recently released guidelines on heart failure therapy: the HCN-channel inhibitor ivabradine and the combined angiotensin and neprilysin inhibitor valsartan/sacubitril. New compounds that are in phase II or III clinical evaluation include novel non-steroidal mineralocorticoid receptor antagonists, guanylate cyclase activators or myosine activators. A variety of novel candidate targets have been identified and the availability of gene transfer has just begun to accelerate translation from basic science to clinical application. This review provides an overview of current pharmacology and pharmacotherapy in chronic heart failure at three stages: the updated clinical guidelines of the American Heart Association and the European Society of Cardiology, new drugs which are in clinical development, and finally innovative drug targets and their mechanisms in heart failure which are emerging from preclinical studies will be discussed.

  6. The antihypertensive effectiveness and safety of dual RAAS blockade with aliskiren and valsartan.

    Science.gov (United States)

    Chrysant, Steven G

    2010-03-01

    The renin-angiotensin-aldosterone system (RAAS) is a major factor for the development and maintenance of hypertension and a major cause for cardiovascular remodeling and cardiovascular complications through its active peptide angiotensin (Ang) II. Blockade of RAAS with ACE inhibitors (ACEIs) results in suppression of Ang II levels, which eventually return to baseline levels after prolonged ACEI administration. This leads to an escape phenomenon through generation of Ang II from enzymes other than ACE and led to the hypothesis that dual blockade of RAAS with an ACEI/Ang receptor blocker (ARB) combination could lead to total blockade of RAAS, since ARBs block the action of Ang II at the AT1 receptor level, irrespective of the mechanism of Ang II generation and will have an additive blood pressure (BP)-lowering effect. However, this hypothesis has not materialized clinically, as the ACEI/ARB combination produces modest BP reductions that are not significantly greater than monotherapy with the component drugs, and is frequently associated with higher incidence of side effects. A new dual RAAS blockade with the direct renin inhibitor aliskiren and the ARB valsartan produces greater BP reductions than monotherapy with the component drugs and is safe and well tolerated. The combination of aliskiren with valsartan, and with other antihypertensive drugs is discussed.

  7. Nephroprotection by Hypoglycemic Agents: Do We Have Supporting Data?

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    Jose Luis Górriz

    2015-10-01

    Full Text Available Current therapy directed at delaying the progression of diabetic nephropathy includes intensive glycemic and optimal blood pressure control, renin angiotensin-aldosterone system blockade and multifactorial intervention. However, the renal protection provided by these therapeutic modalities is incomplete. There is a scarcity of studies analysing the nephroprotective effect of antihyperglycaemic drugs beyond their glucose lowering effect and improved glycaemic control on the prevention and progression of diabetic nephropathy. This article analyzes the exisiting data about older and newer drugs as well as the mechanisms associated with hypoglycemic drugs, apart from their well known blood glucose lowering effect, in the prevention and progression of diabetic nephropathy. Most of them have been tested in humans, but with varying degrees of success. Although experimental data about most of antihyperglycemic drugs has shown a beneficial effect in kidney parameters, there is a lack of clinical trials that clearly prove these beneficial effects. The key question, however, is whether antihyperglycemic drugs are able to improve renal end-points beyond their antihyperglycemic effect. Existing experimental data are post hoc studies from clinical trials, and supportive of the potential renal-protective role of some of them, especially in the cases of dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. Dedicated and adequately powered renal trials with renal outcomes are neccessary to assess the nephrotection of antihyperglycaemic drugs beyond the control of hyperglycaemia.

  8. Can medications be safely withdrawn in patients with stable chronic heart failure? systematic review and meta-analysis.

    Science.gov (United States)

    Hopper, Ingrid; Samuel, Rohit; Hayward, Christopher; Tonkin, Andrew; Krum, Henry

    2014-07-01

    Heart failure (HF) therapy involves use of multiple medications. There is little guidance on the safety and impact on clinical outcomes of stopping HF medications. A comprehensive systematic search for studies of drug therapy withdrawal in HF was performed. Meta-analysis of the risk ratio (RR) was performed with the use of the Mantel-Haenszel random effects model for all-cause mortality and cardiovascular outcomes. Twenty-six studies met the inclusion criteria. Studies on withdrawal of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers in HF are scarce and small, yet show relatively convincingly that such withdrawals have untoward effects on cardiac structure, symptoms, and major outcomes. Meta-analysis of 7 studies of digoxin withdrawal (2,987 participants) without background beta-blocker showed increased HF hospitalizations (RR 1.30, 95% confidence interval [CI] 1.16-1.46; P medications could be successfully withdrawn after recovery. Current evidence discourages any attempt to discontinue RAAS inhibitors or beta-blockers in patients with stable HF, regardless of clinical and/or echocardiographic status. Formal withdrawal trials of other classes are needed. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Sacubitril/Valsartan: A Novel Cardiovascular Combination Agent.

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    Sible, Alexandra M; Nawarskas, James J; Alajajian, David; Anderson, Joe R

    2016-01-01

    Sacubitril/valsartan [LCZ696 (Entresto), Novartis Pharmaceuticals Corp.] is the first in a new class of drugs that combines neprilysin inhibition with angiotensin II receptor antagonism, the combination of which acts to increase endogenous natriuretic peptides while inhibiting the renin-angiotensin-aldosterone system. Sacubitril/valsartan has been studied in the treatment of hypertension, heart failure with reduced ejection fraction (HFrEF), and heart failure with preserved ejection fraction (HFpEF) and has demonstrated clinical efficacy in blood pressure reduction in hypertensive patients with and without HFpEF and a reduction in hospitalizations and mortality for patients with HFrEF. Research to evaluate clinical outcomes in HFpEF is ongoing. Sacubitril/valsartan is approved to reduce hospitalization and risk of cardiovascular death for patients with HFrEF in New York Heart Association (NYHA) functional class II-IV. The product is as well tolerated as an angiotensin-converting enzyme inhibitor, with the most common side effect being hypotension. Expectedly, it is much more costly than generic angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, which will be a factor in determining how widespread the use of this agent will be. In summary, although the number of published studies evaluating its use is limited, sacubitril/valsartan represents a promising new treatment option for patients with HFrEF. Ongoing studies will continue to refine the role of this agent in clinical practice.

  10. Azilsartan alone and in combination for the treatment of hypertension – clinical utility and patient considerations

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    Jones JD

    2013-08-01

    Full Text Available Jocelyn D Jones,1 Sylvia H Jackson,1 Charlie Colquitt21College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Jacksonville, FL, USA; 2College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tampa, FL, USAAbstract: Hypertension is a common disease that leads to significant cardiovascular morbidity and mortality. Adequate blood pressure control is essential in preventing end organ complications. One of the most popular antihypertensive strategies for the treatment of elevated blood pressure is to attenuate the actions of the renin-angiotensin-aldosterone system. The agents include the angiotensin converting enzyme inhibitors, angiotensin II receptor blockers (ARBs, direct renin inhibitors, and aldosterone antagonists. The ARBs inhibit the action of angiotensin II by binding to the angiotensin II type 1 receptor. The inhibition of angiotensin II results in a dose dependent decrease in peripheral resistance, reduction in vascular smooth muscle contraction, and reduced synthesis of aldosterone in the kidneys. Azilsartan medoxomil is a highly selective ARB. It was approved by the US Food and Drug Administration in February 2011 for the treatment of hypertension in adults. It is the eighth ARB to be added to the market. This article will discuss the pharmacologic and clinical characteristics of azilsartan medoxomil to help differentiate it from other ARBs that are used for the management of hypertension.Keywords: hypertension, azilsartan medoxomil, angiotensin II receptor blocker, ARB

  11. Cardiovascular effects of the angiotensin type 2 receptor.

    Science.gov (United States)

    Faria-Costa, Gabriel; Leite-Moreira, Adelino; Henriques-Coelho, Tiago

    2014-01-01

    The angiotensin type 2 receptor, AT2R, has been described as having opposite effects to the angiotensin type 1 receptor, AT1R. Although the quantities of the AT2R found in the adult are low, its expression rises in pathological situations. The AT2R has three major signaling pathways: activation of serine/threonine phosphatases (promoting apoptosis and antioxidant effects), activation of the bradykinin/NO/cGMP pathway (promoting vasodilation), and activation of phospholipase A2 (associated with regulation of potassium currents). The AT2R appears to have effects in vascular remodeling, atherosclerosis prevention and blood pressure lowering (when associated with an AT1R inhibitor). After myocardial infarction, the AT2R appears to decrease infarct size, cardiac hypertrophy and fibrosis, and to improve cardiac function. However, its role in the heart is controversial. In the kidney, the AT2R promotes natriuresis. Until now, treatment directed at the renin-angiotensin-aldosterone system has been based on angiotensin-converting enzyme inhibitors or angiotensin type 1 receptor blockers. The study of the AT2R has been revolutionized by the discovery of a direct agonist, C21, which promises to become part of the treatment of cardiovascular disease. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  12. Cardiac and Renal Effects of Atrasentan in Combination with Enalapril and Paricalcitol in Uremic Rats

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    Cynthia Ritter

    2014-09-01

    Full Text Available Background/Aims: The search for new therapies providing cardiorenal protection in chronic kidney disease (CKD has led to treatments that combine conventional renin-angiotensin-aldosterone-system inhibitors with other drugs that exhibit potential in disease management. Methods: In rats made uremic by renal ablation, we examined the effects of addition of the endothelin-A receptor antagonist atrasentan to a previously examined combination of enalapril (angiotensin converting enzyme inhibitor and paricalcitol (vitamin D receptor activator on cardiac and renal parameters. The effects of the individual and combined drugs were examined after a 3-month treatment. Results: A decrease in systolic blood pressure, serum creatinine and proteinuria, and improvement of renal histology in uremic rats were attributed to enalapril and/or paricalcitol treatment; atrasentan alone had no effect. In heart tissue, individual treatment with the drugs blunted the increase in cardiomyocyte size, and combined treatment additively decreased cardiomyocyte size to normal levels. Perivascular fibrosis was blunted in uremic control rats with atrasentan or enalapril treatment. Conclusions: We found distinct cardiac and renal effects of atrasentan. Combination treatment with atrasentan, enalapril and paricalcitol provided positive effects on cardiac remodeling in uremic rats, whereas combination treatment did not offer further protective effects on blood pressure, proteinuria or renal histology.

  13. Use of Valsartan in Post-Myocardial Infarction and Heart Failure Patients

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    Peter P Liu

    2006-03-01

    Full Text Available Left ventricular (LV dysfunction and/or heart failure (HF are frequent complications of hypertension and myocardial infarction (MI, placing affected patients at increased risk of significant morbidity and premature death. Given that the renin-angiotensin-aldosterone system (RAAS is activated and of pathophysiological importance in such patients, a strong therapeutic rationale exists to target the main effector mechanism (that is, angiotensin II [Ang II] in order to lessen the associated morbidity and mortality burden.Angiotensin-converting enzyme (ACE inhibitors have been shown to reduce mortality and LV dysfunction and to slow disease progression in patients with HF, including high-risk, post-MI patients. However, ACE inhibitors (ACE-Is may not provide optimal long-term RAAS blockade (a finding that is associated with a worse prognosis such and many patients are unable to tolerate such therapy (because of troublesome dry cough, for example. In contrast, Ang II receptor blockers (ARBs may block the RAAS more completely than ACE-Is and appear to be better tolerated. Several large-scale trials have evaluated the efficacy of ARBs in patients with LV dysfunction and/or HF (including high-risk, post-MI patients, and have confirmed their utility as an R efficacious and well-tolerated alternative to ACE-Is in this setting.

  14. Angiotensin receptor neprilysin inhibition in heart failure: mechanistic action and clinical impact.

    Science.gov (United States)

    Buggey, Jonathan; Mentz, Robert J; DeVore, Adam D; Velazquez, Eric J

    2015-09-01

    Heart failure (HF) is an increasingly common syndrome associated with high mortality and economic burden, and there has been a paucity over the past decade of new pharmacotherapies that improve outcomes. However, recent data from a large randomized controlled trial compared the novel agent LCZ696, a dual-acting angiotensin receptor blocker and neprilysin inhibitor (ARNi), with the well established angiotensin-converting enzyme (ACE) inhibitor enalapril and found significant reduction in mortality among the chronic reduced ejection fraction HF population. Preclinical and clinical data suggest that neprilysin inhibition provides beneficial outcomes in HF patients by preventing the degradation of natriuretic peptides and thereby promoting natriuresis and vasodilatation and counteracting the negative cardiorenal effects of the up-regulated renin-angiotensin-aldosterone system. Agents such as omapatrilat combined neprilysin and ACE inhibition but had increased rates of angioedema. Goals of an improved safety profile provided the rationale for the development of the ARNi LCZ696. Along with significant reductions in mortality and hospitalizations, clinical trials suggest that LCZ696 may improve surrogate markers of HF severity. In this paper, we review the preclinical and clinical data that led to the development of LCZ696, the understanding of the underlying mechanistic action, and the robust clinical impact that LCZ696 may have in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Association of Genetic Polymorphisms of Renin–Angiotensin–Aldosterone System-Related Genes with Arterio-Venous Fistula Malfunction in Hemodialysis Patients

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    Yu-Wei Chen

    2016-05-01

    Full Text Available Hemodialysis (HD is the most commonly-used renal replacement therapy for patients with end-stage renal disease worldwide. Arterio-venous fistula (AVF is the vascular access of choice for HD patients with lowest risk of infection and thrombosis. In addition to environmental factors, genetic factors may also contribute to malfunction of AVF. Previous studies have demonstrated the effect of genotype polymorphisms of angiotensin converting enzyme on vascular access malfunction. We conducted a multicenter, cross-sectional study to evaluate the association between genetic polymorphisms of renin-angiotensin-aldosterone system and AVF malfunction. Totally, 577 patients were enrolled. Their mean age was 60 years old and 53% were male. HD patients with AVF malfunction had longer duration of HD (92.5 ± 68.1 vs. 61.2 ± 51.9 months, p < 0.001, lower prevalence of hypertension (44.8% vs. 55.3%, p = 0.025, right-sided (31.8% vs. 18.4%, p = 0.002 and upper arm AVF (26.6% vs. 9.7%, p < 0.001, and higher mean dynamic venous pressure (DVP (147.8 ± 28.3 vs. 139.8 ± 30.0, p = 0.021. In subgroup analysis of different genders, location of AVF and DVP remained significant clinical risk factors of AVF malfunction in univariate and multivariate binary logistic regression in female HD patients. Among male HD patients, univariate binary logistic regression analysis revealed that right-side AVF and upper arm location are two important clinical risk factors. In addition, two single nucleotide polymorphisms (SNPs, rs275653 (Odds ratio 1.90, p = 0.038 and rs1492099 (Odds ratio 2.29, p = 0.017 of angiotensin II receptor 1 (AGTR1, were associated with increased risk of AVF malfunction. After adjustment for age and other clinical factors, minor allele-containing genotype polymorphisms (AA and CA of rs1492099 still remained to be a significant risk factor of AVF malfunction (Odds ratio 3.63, p = 0.005. In conclusion, we demonstrated that rs1492099, a SNP of AGTR1 gene, could

  16. Effects of cilnidipine on sympathetic nerve activity and cardiorenal function in hypertensive patients with type 2 diabetes mellitus: association with BNP and aldosterone levels.

    Science.gov (United States)

    Tanaka, Masami; Sekioka, Risa; Nishimura, Takeshi; Ichihara, Atsuhiro; Itoh, Hiroshi

    2014-12-01

    Hypertension stimulates the sympathetic nervous system and this phenomenon is exacerbated by diabetes mellitus. We investigated the effects of cilnidipine, an N/L-type calcium channel blocker, on aspects of this system in patients with type 2 diabetes mellitus. In 33 hypertensive patients with type 2 diabetes mellitus treated with a calcium channel blocker other than cilnidipine, we evaluated the influence of switching to cilnidipine on blood pressure, heart rate, catecholamine, plasma renin and aldosterone concentration, brain natriuretic peptide, urine liver-type fatty acid binding protein, and urinary albumin excretion ratio in the same patients by a cross-over design. Other biochemical parameters were also evaluated. Switching to cilnidipine did not change blood pressure but caused reduction in catecholamine concentrations in blood and urine and plasma aldosterone concentration, accompanied by significant reduction in brain natriuretic peptide, urine liver-type fatty acid binding protein, and albumin excretion ratio. These parameters other than brain natriuretic peptide were significantly increased after cilnidipine was changed to the original calcium channel blocker. In 33 hypertensive patients with type 2 diabetes mellitus, compared to other calcium channel blockers, cilnidipine suppressed sympathetic nerve activity and aldosterone, and significantly improved markers of cardiorenal disorders. Therefore, cilnidipine may be an important calcium channel blocker for use in combination with renin-angiotensin-aldosterone system inhibitors when dealing with hypertension complicated with diabetes mellitus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Hypertension in children with end-stage renal disease.

    Science.gov (United States)

    Roszkowska-Blaim, Maria; Skrzypczyk, Piotr

    2015-09-01

    This review summarizes current data on the epidemiology, pathophysiology, and treatment of hypertension (HTN) in children with end-stage renal disease (ESRD). Worldwide prevalence of ESRD ranges from 5.0 to 84.4 per million age-related population. HTN is present in 27-79% of children with ESRD, depending on the modality of renal replacement therapy and the exact definition of hypertension. Ambulatory BP monitoring has been recommended for the detection of HTN and evaluation of treatment effectiveness. HTN in dialyzed patients is mostly related to hypervolemia, sodium overload, activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, impaired nitric oxide synthesis, reduced vitamin D levels, and effects of microRNA. In children undergoing chronic dialysis therapy, important factors include optimization of renal replacement therapy and preservation of residual renal function, allowing reduction of volume- and sodium-overload, along with appropriate drug treatment, particularly with calcium channel blockers, RAAS inhibitors, and loop diuretics.

  18. GENETIC PREDICTORS OF ATRIAL FIBRILLATION

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    A. V. Kuskaeva

    2016-01-01

    Full Text Available Atrial fibrillation (AF is the most common heart rhythm disturbance. It is believed that the primary form of AF is genetically determined in most cases, but the genetic component cannot be excluded in the secondary form of AF. AF is a heterogeneous disease and many authors proved its relationship with other genetic heart disease. In most cases, certain combinations of polymorphisms of different genes promote the development of AF. The study of genes of renin-angiotensin-aldosterone system (RAAS is especially important, because the role of this system in AF pathogenesis is currently studding most intensively. These studies are of great practical interest, as associative effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the prevention of AF is revealed. RAAS blockers are able not only to reduce the risk of new-onset AF in hypertensive and normotensive patients but also prevent recurrence of AF. Furthermore, experimental studies showed that RAAS blockers prevent not only the remodeling of the left ventricle, and also the left atrium, pointing to the pathogenesis of AF. So, screening for susceptibility genes and the study of their polymorphism is currently an important focus in the study of AF.

  19. A patient with heart failure and worsening kidney function.

    Science.gov (United States)

    Sarnak, Mark J

    2014-10-07

    There is high prevalence of CKD, defined by reduced GFR, in patients with heart failure. Reduced kidney function is associated with increased morbidity and mortality in this patient population. The cardiorenal syndrome (CRS) involves a bidirectional relationship between the heart and kidneys whereby dysfunction in either may exacerbate the function of the other, but this syndrome has been difficult to precisely define because it has many complex physiologic, biochemical, and hormonal abnormalities. The pathophysiology of CRS is not completely understood, but potential mechanisms include reduced kidney perfusion due to decreased forward flow, increased right ventricular and venous pressure, and neurohormonal adaptations. Treatment options include inotropic medications; diuretics; ultrafiltration; and medications, such as β-blockers, inhibitors of the renin-angiotensin-aldosterone system, and more novel treatments that focus on unique aspects of the pathophysiology. Recent observational studies suggest that treatments that result in a decrease in venous pressure and lead to hemoconcentration may be associated with improved outcomes. Patients with CRS that is not responsive to medical interventions should be considered for ventricular assist devices, heart transplantation, or combined heart and kidney transplantation.

  20. Perspective of future drugs targeting sterile 20/SPS1-related proline/alanine-rich kinase for blood pressure control

    Science.gov (United States)

    Lin, Gen-Min; Liu, Pang-Yen; Wu, Ching-Fen; Wang, Wen-Been; Han, Chih-Lu

    2015-01-01

    According to a genome-wide association study, intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase (SPAK) gene was linked to 20% of the general population and may be associated with elevated blood pressure. As cell volume changes, mammalian SPAK kinases respond to phosphorylate and regulate cation-coupled chloride co-transporter activity. To our knowledge, phosphorylation of upstream with-no-lysine (K) (WNK) kinases would activate SPAK kinases. The activation of WNK-OSR1/SPAK cascade on the kidneys and aortic tissue is related to the development of hypertension. Several regulators of the WNK pathway such as the Kelch kinase protein 3 - Cullin 3 E3 ligase, hyperinsulinemia, and low potassium intake to mediate hypertension have been identified. In addition, the SPAK kinases may affect the action of renin-angiotensin-aldosterone system on blood pressure as well. In 2010, two SPAK knock-in and knock-out mouse models have clarified the pathogenesis of lowering blood pressure by influencing the receptors on the kidneys and aortic smooth muscle. More recently, two novel SPAK inhibitors for mice, Stock 1S-14279 and Closantel were discovered in 2014. Targeting of SPAK seems to be promising for future antihypertensive therapy. Therefore we raised some viewpoints for the issue for the antihypertensive therapy on the SPAK (gene or kinase). PMID:26131334

  1. Patiromer: a significant advance in the management of hyperkalemia.

    Science.gov (United States)

    Paton, D M

    2015-12-01

    The U.S. Food and Drug Administration (FDA) approved patiromer to treat hyperkalemia on October 21, 2015, making it the first agent approved for this condition in 50 years. Patiromer was developed by Relypsa, Inc. The active ingredient is patiromer sorbitex calcium which consists of the active moiety, patiromer, a nonabsorbed potassium-binding polymer, and a calcium-sorbitol counterion. In the colon, patiromer exchanges calcium for potassium thus causing a fall in serum potassium. Trials have shown that patiromer reduces serum potassium in patients with mild, moderate and moderate to severe hyperkalemia to the normal range. It has also been used successfully in patients with chronic kidney disease and/or heart failure. It has also allowed the use of the mineralocorticoid antagonist spironolactone in full dosage in patients with chronic kidney disease and/or heart failure who were already receiving a renin-angiotensin-aldosterone system inhibitor. Adverse effects have mostly been gastrointestinal in nature and have not caused patients to discontinue treatment in unacceptable numbers.

  2. Combination therapy in hypertension: An update

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    Kalra Sanjay

    2010-06-01

    Full Text Available Abstract Meticulous control of blood pressure is required in patients with hypertension to produce the maximum reduction in clinical cardiovascular end points, especially in patients with comorbidities like diabetes mellitus where more aggressive blood pressure lowering might be beneficial. Recent clinical trials suggest that the approach of using monotherapy for the control of hypertension is not likely to be successful in most patients. Combination therapy may be theoretically favored by the fact that multiple factors contribute to hypertension, and achieving control of blood pressure with single agent acting through one particular mechanism may not be possible. Regimens can either be fixed dose combinations or drugs added sequentially one after other. Combining the drugs makes them available in a convenient dosing format, lower the dose of individual component, thus, reducing the side effects and improving compliance. Classes of antihypertensive agents which have been commonly used are angiotensin receptor blockers, thiazide diuretics, beta and alpha blockers, calcium antagonists and angiotensin-converting enzyme inhibitors. Thiazide diuretics and calcium channel blockers are effective, as well as combinations that include renin-angiotensin-aldosterone system blockers, in reducing BP. The majority of currently available fixed-dose combinations are diuretic-based. Combinations may be individualized according to the presence of comorbidities like diabetes mellitus, chronic renal failure, heart failure, thyroid disorders and for special population groups like elderly and pregnant females.

  3. Junctional Bradycardia as Early Sign of Digoxin Toxicity in a Premature Infant with Congestive Heart Failure due to a Left to Right Shunt.

    Science.gov (United States)

    Dasgupta, Soham; Aly, Ashraf M; Jain, Sunil K

    2016-03-01

    Introduction Congestive heart failure due to left to right cardiac shunt is usually managed medically with diuretics, angiotensin converting enzyme inhibitors, and, in some cases, with the addition of digoxin. Case We report a 31-week gestation premature male infant who did not respond to such treatment and developed hyperaldosteronism and severe hypokalemia secondary to activation of the renin angiotensin aldosterone system. The hypokalemia was not responsive to intravenous KCL supplementation and induced digoxin toxicity despite a relatively normal digoxin level. The earliest signs of digoxin toxicity in the patient were junctional rhythm and bradycardia. The discontinuation of digoxin and the administration of digoxin specific immunoglobulin fragments (Fab) reversed those changes. The addition of spironolactone (an aldosterone antagonist) had a dramatic effect, resulting in clinical improvement of the patient coupled with normalization of Q4 serum and urine electrolytes. Conclusion Serum Digoxin level alone may fail as an independent guide in the diagnosis of digoxin toxicity when hypokalemia is present. In premature infants with congestive heart failure and hypokalemia, addition of an aldosterone antagonist should be considered.

  4. Perspective of future drugs targeting sterile 20/SPS1-related proline/alanine-rich kinase for blood pressure control

    Institute of Scientific and Technical Information of China (English)

    Gen-Min; Lin; Pang-Yen; Liu; Ching-Fen; Wu; Wen-Been; Wang; Chih-Lu; Han

    2015-01-01

    According to a genome-wide association study,intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase(SPAK) gene was linked to 20% of the general population and may be associated with elevated blood pressure. As cell volume changes,mammalian SPAK kinases respond to phosphorylate and regulate cation-coupled chloride co-transporter activity. To our knowledge,phosphorylation of upstream with-no-lysine(K)(WNK) kinases would activate SPAK kinases. The activation of WNK-OSR1/SPAK cascade on the kidneys and aortic tissue is related to the development of hypertension. Several regulators of the WNK pathway such as the Kelch kinase protein 3-Cullin 3 E3 ligase,hyperinsulinemia,and low potassium intake to mediate hypertension have been identified. In addition,the SPAK kinases may affect the action of renin-angiotensin-aldosterone system on blood pressure as well. In 2010,two SPAK knock-in and knock-out mouse models have clarified the pathogenesis of lowering blood pressure by influencing the receptors on the kidneys and aortic smooth muscle. More recently,two novel SPAK inhibitors for mice,Stock 1S-14279 and Closantel were discovered in 2014. Targeting of SPAK seems to be promising for future antihypertensive therapy. Therefore we raised some viewpoints for the issue for the antihypertensive therapy on the SPAK(gene or kinase).

  5. Sacubitril/valsartan (LCZ696) for the treatment of heart failure.

    Science.gov (United States)

    Gori, Mauro; Senni, Michele

    2016-01-01

    The PARADIGM-HF study, a large outcome trial in heart failure and reduced ejection fraction (HFrEF), has recently shown improved cardiovascular outcomes with sacubitril/valsartan (Entresto®, Novartis), still commonly referred to as LCZ696, compared to ACE-inhibitor therapy, possibly leading us to a new era for heart failure (HF) treatment. LCZ696 represents a first-in-class drug acting through inhibition of angiotensin receptor and neprilysin, thus modulating the renin angiotensin aldosterone system and vasoactive substances such as natriuretic peptides. Based on the PARADIGM-HF results, the FDA recently approved LCZ696 as an effective means to reduce the burden of HF with reduced ejection fraction. Furthermore, these data also provided rationale to test LCZ696 in an ongoing trial with HF and preserved ejection fraction. Despite the enthusiasm regarding this novel compound, real world data on its efficacy and safety are eagerly expected. This article summarizes all evidences regarding LCZ696 and how to implement this new drug in the current HF armamentarium.

  6. [Monitoring of cardiovascular risk factors in patients with diabetes type 2].

    Science.gov (United States)

    Petrlová, B; Rosolová, H; Simon, J; Sefrna, F; Sifalda, P; Sípová, I

    2009-09-01

    The control of basic cardiovascular risk factors was examined in a sample of 415 diabetes type 2 patients, aged 66 +/- 10 years, with a 9.4 +/- 8 years long history of diabetes, both genders represented proportionally; 95% of the sample were hypertensive. The recommended blood pressure value was achieved by 13% males and 17% females. Antihypertensive monotherapy was indicated in 40% of the sample. Renin-angiotensin-aldosteron system inhibitors were prescibed to 90% of the sample. The fasting glycaemia < or = 6 mmol/L were achieved in 10% males and 11% females; glycosilated hemoglobin < 4.5% in 20% males and 24% females; 60% of the sample had antidiabetic pharmacotherapy--44% males and 48% females used metformin. Total fasting plasma cholesterol < 4.5 mmol/L was achieved in 31% males and 23% females; LDL-cholesterol < 2.5 mmol/L was achieved in 31% males and 41% females. The target values for diabetics in secondary prevention of cardiovascular diseases or with subclinical atherosclerosis was achieved in 13% of the sample. Statins were prescribed in 60% of the sample, fibrates in 4%. Only 2 females achieved all the target values. Hypolipidemic and antihypertensive drug therapy is unsatisfactory; there is certainly a big potential in life style changes among the diabetic patients.

  7. Current Challenges in Diabetic Nephropathy: Early Diagnosis and Ways to Improve Outcomes.

    Science.gov (United States)

    Kim, Sang Soo; Kim, Jong Ho; Kim, In Joo

    2016-06-01

    Diabetes is often associated with chronic kidney disease (CKD) and is the primary cause of kidney failure in half of patients who receive dialysis therapy. Given the increasing prevalence of diabetes and its high morbidity and mortality, diabetic nephropathy is a serious drawback in individual patients and a tremendous socioeconomic burden on society. Despite growing concern for the management of diabetic nephropathy, the prevalence of CKD with diabetes is the same today as it was 20 years ago. The current strategy to manage diabetic nephropathy, including the control of hyperglycemia, dyslipidemia, and blood pressure and the wide-spread use of renin-angiotensin-aldosterone system inhibitors, is well established to be beneficial in the early stages of diabetic nephropathy. However, the effects are uncertain in patients with relatively progressed CKD. Therefore, early diagnosis or risk verification is extremely important in order to reduce the individual and socioeconomic burdens associated with diabetic nephropathy by providing appropriate management to prevent the development and progression of this condition. This review focuses on recent research and guidelines regarding risk assessment, advances in medical treatment, and challenges of and future treatments for diabetic nephropathy.

  8. Has RAAS Blockade Reached Its Limits in the Treatment of Diabetic Nephropathy?

    Science.gov (United States)

    Majewski, Collen; Bakris, George L

    2016-04-01

    Medications that block the renin-angiotensin-aldosterone system (RAAS) are a cornerstone of diabetic nephropathy treatment. These agents play an important role in slowing the nephropathy progression in patients with diabetes. Clinical outcome trials that investigated use of these drug classes in patients with diabetic nephropathy have demonstrated clinical significant benefit in slowing nephropathy progression only in people with >300 mg/day of proteinuria. Thus, guidelines mandate their use in such patients. Conversely, combinations of RAAS blocking agents in these patients can worsen renal outcomes. Moreover, use of RAAS blockers in patients with a glomerular filtration rate below 45 mL/min/1.73 m(2) is limited by hyperkalemia. New agents that predictably bind excess potassium in the colon offer the possibility of extending RAAS inhibitor use in advanced chronic kidney disease (CKD) to allow evaluation of RAAS blockade for nephropathy and cardiovascular outcomes. These new potassium-binding agents may provide an opportunity to continue full-dose RAAS inhibition and assess if the benefits of RAAS blockade seen in stage 3 CKD can be extrapolated to persons with stages 4 and 5 CKD, not previously tested due to hyperkalemia.

  9. Aerobic Exercise and Pharmacological Therapies for Skeletal Myopathy in Heart Failure: Similarities and Differences

    Directory of Open Access Journals (Sweden)

    Aline V. Bacurau

    2016-01-01

    Full Text Available Skeletal myopathy has been identified as a major comorbidity of heart failure (HF affecting up to 20% of ambulatory patients leading to shortness of breath, early fatigue, and exercise intolerance. Neurohumoral blockade, through the inhibition of renin angiotensin aldosterone system (RAS and β-adrenergic receptor blockade (β-blockers, is a mandatory pharmacological therapy of HF since it reduces symptoms, mortality, and sudden death. However, the effect of these drugs on skeletal myopathy needs to be clarified, since exercise intolerance remains in HF patients optimized with β-blockers and inhibitors of RAS. Aerobic exercise training (AET is efficient in counteracting skeletal myopathy and in improving functional capacity and quality of life. Indeed, AET has beneficial effects on failing heart itself despite being of less magnitude compared with neurohumoral blockade. In this way, AET should be implemented in the care standards, together with pharmacological therapies. Since both neurohumoral inhibition and AET have a direct and/or indirect impact on skeletal muscle, this review aims to provide an overview of the isolated effects of these therapeutic approaches in counteracting skeletal myopathy in HF. The similarities and dissimilarities of neurohumoral inhibition and AET therapies are also discussed to identify potential advantageous effects of these combined therapies for treating HF.

  10. Clinical Evidence for the Cardiovascular Benefits of Angiotensin Receptor Blockers

    Directory of Open Access Journals (Sweden)

    Georg Nickenig

    2006-03-01

    Full Text Available Targeting the renin-angiotensin-aldosterone system (RAAS, specifically the effector peptide angiotensin II (Ang II, represents a major opportunity for slowing the progression of cardiovascular disease (CVD and, in turn, reducing the risk of morbidity and mortality. Inhibition of angiotensin-converting enzyme (ACE and selective blockade of Ang II AT1 receptors are two approaches through which the pathophysiological effects of Ang II can be targeted. Numerous clinical studies have established the benefits of ACE inhibitors P, (ACE-Is in lessening the morbidity and mortality burden of CVD. There are, however, tolerability concerns associated with ACE-Is, such as angioedema and dry cough. By blocking Ang II at the AT1 receptor level, Ang II receptor blockers (ARBs provide a more specific and complete blockade of the deleterious effects of Ang II and tend to have more favourable tolerability. A number of clinical trials have shown that ARBs are not only associated with positive outcomes across the CVD continuum but may also have a role in the prevention or delay of diabetes (a major cardiovascular risk factor. Ongoing trials are aiming to define the place of such agents in lessening morbidity and mortality from CVD.

  11. Folding in solution of the C-catalytic protein fragment of angiotensin-converting enzyme.

    Science.gov (United States)

    Vamvakas, Sotirios-Spyridon M; Leondiadis, Leondios; Pairas, George; Manessi-Zoupa, Evy; Spyroulias, Georgios A; Cordopatis, Paul

    2009-08-01

    Angiotensin-converting enzyme (ACE) is a key molecule of the renin-angiotensin-aldosterone system which is responsible for the control of blood pressure. For over 30 years it has become the target for fighting off hypertension. Many inhibitors of the enzyme have been synthesized and used widely in medicine despite the lack of ACE structure. The last 5 years the crystal structure of ACE separate domains has been revealed, but in order to understand how the enzyme works it is necessary to study its structure in solution. We present here the cloning, overexpression in Escherichia coli, purification and structural study of the Ala(959) to Ser(1066) region (ACE_C) that corresponds to the C-catalytic domain of human somatic angiotensin-I-converting enzyme. ACE_C was purified under denatured conditions and the yield was 6 mg/l of culture. Circular dichroism (CD) spectroscopy indicated that 1,1,1-trifluoroethanol (TFE) is necessary for the correct folding of the protein fragment. The described procedure can be used for the production of an isotopically labelled ACE(959-1066) protein fragment in order to study its structure in solution by NMR spectroscopy.

  12. Current Challenges in Diabetic Nephropathy: Early Diagnosis and Ways to Improve Outcomes

    Directory of Open Access Journals (Sweden)

    Sang Soo Kim

    2016-06-01

    Full Text Available Diabetes is often associated with chronic kidney disease (CKD and is the primary cause of kidney failure in half of patients who receive dialysis therapy. Given the increasing prevalence of diabetes and its high morbidity and mortality, diabetic nephropathy is a serious drawback in individual patients and a tremendous socioeconomic burden on society. Despite growing concern for the management of diabetic nephropathy, the prevalence of CKD with diabetes is the same today as it was 20 years ago. The current strategy to manage diabetic nephropathy, including the control of hyperglycemia, dyslipidemia, and blood pressure and the wide-spread use of renin-angiotensin-aldosterone system inhibitors, is well established to be beneficial in the early stages of diabetic nephropathy. However, the effects are uncertain in patients with relatively progressed CKD. Therefore, early diagnosis or risk verification is extremely important in order to reduce the individual and socioeconomic burdens associated with diabetic nephropathy by providing appropriate management to prevent the development and progression of this condition. This review focuses on recent research and guidelines regarding risk assessment, advances in medical treatment, and challenges of and future treatments for diabetic nephropathy.

  13. Tagging SNPs in REN, AGTR1 and AGTR2 genes and response of renin activity, angiotensin II and aldosterone concentrations to antihypertensive treatment in Kazakans.

    Science.gov (United States)

    Yan, Weili; Zhang, Yuanming; Shan, Zimei; Wang, Qian; Huang, Yongdi; Wang, Chenchen; Yan, Kai

    2011-12-01

    Polymorphisms of REN, AGTR1 and AGTR2 may be associated with responses of renin-angiotensin-aldosterone system (RAAS) activity phenotypes to angiotensin-converting enzyme inhibitor (ACEI) antihypertensive treatment. A total of 400 first diagnosed Kazak hypertensives were randomly allocated to two groups and received a 3-week course of either captopril and atenolol as monotherapy under double blinding. Genotype-phenotype association analyses were performed by covariance analyses between baseline level and responses of blood pressure, renin, angiotensin II and aldosterone concentrations with tagging single nucleotide polymorphisms (SNPs) in REN, AGTR1 and AGTR2 genes. A false discovery rate method was used to adjust multiple testing. After adjustment for multiple testing, we found that the G allele of rs6676670 (T/G) in intron 1 of REN was significantly associated with higher baseline aldosterone concentrations (p < 0.0001, explained variance (EV) = 2.3%). Significant associations after adjustments were also found between the A allele of rs2887284, with higher baseline renin activity (p = 0.022, EV = 1.0%), higher responses of renin (p = 0.018 EV = 5.4%), and higher responses of angiotensin II (p = 0.0255, EV = 3.13%) to the treatment of ACEI. The carriers of the A allele of rs2887284 appeared to be more sensitive to the ACEI treatment. rs2887284 in intron 9 of REN is associated with the response of renin and angiotensin II levels to ACEI treatment.

  14. Rationale for nebivolol/valsartan combination for hypertension: review of preclinical and clinical data.

    Science.gov (United States)

    Giles, Thomas D; Cockcroft, John R; Pitt, Bertram; Jakate, Abhijeet; Wright, Harold M

    2017-09-01

    : To treat hypertension, combining two or more antihypertensive drugs from different classes is often necessary. β-Blockers and renin-angiotensin-aldosterone system inhibitors, when combined, have been deemed 'less effective' based on partially overlapping mechanisms of action and limited evidence. Recently, the single-pill combination (SPC) of nebivolol (Neb) 5 mg - a vasodilatory β1-selective antagonist/β3 agonist - and valsartan 80 mg, an angiotensin II receptor blocker, was US Food and Drug Administration-approved for hypertension. Pharmacological profiles of Neb and valsartan, alone and combined, are well characterized. In addition, a large 8-week randomized trial in stages I-II hypertensive patients (N = 4161) demonstrated greater blood pressure-reducing efficacy for Neb/valsartan SPCs than component monotherapies with comparable tolerability. In a biomarkers substudy (N = 805), Neb/valsartan SPCs prevented valsartan-induced increases in plasma renin, and a greater reduction in plasma aldosterone was observed with the highest SPC dose vs. valsartan 320 mg/day. This review summarizes preclinical and clinical evidence supporting Neb/valsartan as an efficacious and well tolerated combination treatment for hypertension.

  15. Potential New Agents for the Management of Hyperkalemia.

    Science.gov (United States)

    Packham, David K; Kosiborod, Mikhail

    2016-02-01

    Hyperkalemia is a common electrolyte disturbance with multiple potential etiologies. It is usually observed in the setting of reduced renal function. Mild to moderate hyperkalemia is usually asymptomatic, but is associated with poor prognosis. When severe, hyperkalemia may cause serious acute cardiac arrhythmias and conduction abnormalities, and may result in sudden death. The rising prevalence of conditions associated with hyperkalemia (heart failure, chronic kidney disease, and diabetes) and broad use of renin-angiotensin-aldosterone system (RAAS) inhibitors and mineralocorticoid receptor antagonists (MRAs), which improve patient outcomes but increase the risk of hyperkalemia, have led to a significant rise in hyperkalemia-related hospitalizations and deaths. Current non-invasive therapies for hyperkalemia either do not remove excess potassium or have poor efficacy and tolerability. There is a clear need for safer, more effective potassium-lowering therapies suitable for both acute and chronic settings. Patiromer sorbitex calcium and sodium zirconium cyclosilicate (ZS-9) are two new potassium-lowering compounds currently in development. Although they have not yet been approved by the US FDA, both have demonstrated efficacy and safety in recent trials. Patiromer sorbitex calcium is a polymer resin and sorbitol complex that binds potassium in exchange for calcium; ZS-9, a non-absorbed, highly selective inorganic cation exchanger, traps potassium in exchange for sodium and hydrogen. This review discusses the merits of both novel drugs and how they may help optimize the future management of patients with hyperkalemia.

  16. Prediction and management of hyperkalemia across the spectrum of chronic kidney disease.

    Science.gov (United States)

    Lazich, Ivana; Bakris, George L

    2014-05-01

    Hyperkalemia commonly limits optimizing treatment to slow stage 3 or higher chronic kidney disease (CKD) progression. The risk of hyperkalemia is linked to dietary potassium intake, level of kidney function, concomitant diseases that may affect potassium balance such as diabetes, and use of medications that influence potassium excretion. The risk predictors for developing hyperkalemia are an estimated glomerular filtration rate of less than 45 mL/min/1.73 m(2) and a serum potassium level greater than 4.5 mEq/L in the absence of blockers of the renin-angiotensin-aldosterone system (RAAS). Generally, monotherapy with RAAS blockers does not increase risk substantially unless hypotension or volume depletion occur. Dual RAAS blockade involving any combination of an angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, renin inhibition, or aldosterone-receptor blocker markedly increases the risk of hyperkalemia in patients with stage 3 or higher CKD. Moreover, dual RAAS blockade further reduces albuminuria by 25% to 30% compared with monotherapy, it has failed to show a benefit on CKD progression or cardiovascular outcome, and thus is not indicated in such patients because of its marked increase in hyperkalemia potential. Although sodium polystyrene resins exist to manage hyperkalemia in patients requiring therapy that increases serum potassium levels, they are not well tolerated. Newer, more predictable, better-tolerated polymers to bind potassium are on the horizon and may be approved within the next 1 to 2 years.

  17. Myocardial infarction: management of the subacute period.

    Science.gov (United States)

    Mercado, Michael G; Smith, Dustin K; McConnon, Michael L

    2013-11-01

    Optimal management of myocardial infarction in the subacute period focuses on improving the discharge planning process, implementing therapies early to prevent recurrent myocardial infarction, and avoiding hospital readmission. Evidence-based guidelines for the care of patients with acute coronary syndrome are not followed up to 25% of the time. Antiplatelet therapy, renin-angiotensin-aldosterone system inhibitors, beta blockers, and statins constitute the foundation of medical therapy. Early noninvasive stress testing is an important risk assessment tool, especially in patients who do not undergo revascularization. Discharge preparation should include a review of medications, referral for exercise-based cardiac rehabilitation, activity recommendations, education about lifestyle modification and recognition of cardiac symptoms, and a clear follow-up plan. Because nonadherence to medications is common in patients after a myocardial infarction and is associated with increased mortality risk, modifiable factors associated with medication self-discontinuation should be addressed before discharge. Structured discharge processes should be used to enhance communication and facilitate the transition from the hospital to the family physician's care.

  18. Diagnosis and treatment of patients with IgA nephropathy in Japan.

    Science.gov (United States)

    Tomino, Yasuhiko

    2016-12-01

    Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people from all racial and ethnic groups. Although CKD is not one specific disease, it is a comprehensive syndrome that includes IgA nephropathy. As reported by the Japanese Society of Nephrology, 13.0 million people have CKD. In Japan, major causes of end-stage kidney disease are type 2 diabetic nephropathy, chronic glomerulonephritis, especially IgA nephropathy, hypertensive nephrosclerosis, and polycystic kidney disease. IgA nephropathy is characterized by polymeric IgA1 with aberrant galactosylation (galactose-deficient IgA1) increased in the blood and deposited in the glomerular mesangial areas, as well as partially in the capillary walls. The tonsils are important as one of the responsible regions in this disease. The clarification of the mechanism of galactose-deficient IgA1 production will pave the way for the development of novel therapies. The results of future research are eagerly awaited. At present, the most important therapeutic goals in patients with IgA nephropathy are the control of hypertension, the decrease of urinary protein excretion, and the inhibition of progression to end-stage kidney disease. Several investigators have reported that renin-angiotensin-aldosterone system inhibitors reduce levels of urinary protein excretion and preserve renal function in patients with IgA nephropathy. In Japan, tonsillectomy and steroid pulse therapy are more effective for patients with IgA nephropathy.

  19. Challenges posed to the maternal circulation by pregnancy

    Directory of Open Access Journals (Sweden)

    Valdés G

    2011-08-01

    Full Text Available Gloria Valdés, Jenny CorthornCentro de Investigaciones Médicas y Departamento Nefrología, Escuela Medicina, Pontificia Universidad Católica, Santiago, ChileAbstract: In primates, adequate growth of the fetus depends on the development of the uteroplacental unit. On the fetal side, this is achieved by the creation of the vascular network of the placenta. On the maternal side, the transformation of the spiral arteries into saccular nonreactive vessels by the trophoblast provides high blood flow to the intervillous space. Apart from the changes in the uterine arteries, the mother expands her plasma volume – at the expense of stimulating the renin-angiotensin-aldosterone system – and her cardiac output. In the maintaining of normotension in the face of an increased cardiac output and plasma volume, the renin-angiotensin-aldosterone system requires an enhanced vasodilator synthesis. Finally, in the late stages of pregnancy, a normal endothelial function is required to provide an ample margin to the activation provoked by deportation of syncytiotrophoblast fragments/factors to the maternal circulation. These four adaptative processes require various interrelated vasodilator systems. Deficient adaptations cause isolated or proteinuric arterial hypertension, intrauterine growth restriction, preterm delivery, and stillbirths, among others. Moreover, a normal or a defective adaptation to pregnancy influences maternal cardiovascular health in later life, as evidenced by various studies, most of them epidemiological; thus, pregnancy is now considered a stress test to the maternal cardiovascular system. Because of this, women planning to become pregnant should be screened for clinical and biochemical cardiovascular risks. Inversely, women presenting with hypertension in pregnancy should be thoroughly studied to detect and correct cardiovascular risks. The incorporation of the predictive value of a hypertensive pregnancy should help reduce

  20. Neurohumoral fluid regulation in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    1998-01-01

    Impaired homeostasis of the blood volume, with increased fluid and sodium retention, is a prevailing element in the deranged systemic and splanchnic haemodynamics in patients with liver disease. In this review, some basic elements of the circulatory changes that take place and of neurohumoral fluid...... oxide and vasodilating peptides seem to play an important role. The development of central hypovolaemia and activation of potent vasoconstricting systems such as the renin-angiotensin-aldosterone system and the sympathetic nervous system lead to a hyperdynamic circulation with increased heart rate...... fluid regulation in chronic liver disease....

  1. Determinants and Changes Associated with Aldosterone Breakthrough after Angiotensin II Receptor Blockade in Patients with Type 2 Diabetes with Overt Nephropathy

    Science.gov (United States)

    Moranne, Olivier; Bakris, George; Fafin, Coraline; Favre, Guillaume; Pradier, Christian

    2013-01-01

    Summary Background and objectives Inhibition of the renin-angiotensin-aldosterone system decreases proteinuria and slows estimated GFR decline in patients with type 2 diabetes mellitus with overt nephropathy. Serum aldosterone levels may increase during renin-angiotensin-aldosterone system blockade. The determinants and consequences of this aldosterone breakthrough remain unknown. Design, setting, participants, & measurements This study examined the incidence, determinants, and changes associated with aldosterone breakthrough in a posthoc analysis of a randomized study that compared the effect of two angiotensin II receptor blockers in patients with type 2 diabetes mellitus with overt nephropathy. Results Of 567 of 860 participants included in this posthoc analysis, 28% of participants developed aldosterone breakthrough, which was defined by an increase greater than 10% over baseline values of serum aldosterone levels after 1 year of angiotensin II receptor blocker treatment. Factors independently associated with aldosterone breakthrough at 1 year were lower serum aldosterone and potassium levels at baseline, higher decreases in sodium intake, systolic BP, and estimated GFR from baseline to 1 year, and use of losartan versus telmisartan. Aldosterone breakthrough at 6 months was not sustained at 1 year in 69% of cases, and it did not predict estimated GFR decrease and proteinuria increase between 6 months and 1 year. Conclusions Aldosterone breakthrough is a frequent event 1 year after initiating renin-angiotensin-aldosterone system blockade, particularly in participants exposed to intensive lowering of BP with sodium depletion and short-acting angiotensin II receptor blockers. Short-term serum aldosterone level increases at 6 months are not associated with negative kidney outcomes between 6 months and 1 year. PMID:23929924

  2. Neurohormonal activation and diagnostic value of cardiac peptides in patients with suspected mild heart failure

    DEFF Research Database (Denmark)

    Mikkelsen, Kirsten V.; Bie, Peter; Møller, Jacob E.;

    2006-01-01

    BACKGROUND: Data describing activation of brain natriuretic peptide (BNP) system relative to the renin-angiotensin-aldosterone system (RAAS) are sparse in the early phase of heart failure (HF). AIMS: To compare activation of BNP system relative to RAAS hyperactivity and to assess diagnostic...... accuracy of cardiac peptides to detect any left ventricular dysfunction (LVD) in patients referred from primary care with suspected HF before institution of medical therapy. METHODS: Of 166 referred patients 150 were consecutively included (14 were excluded and two refused consent). Echocardiography...

  3. Raised Plasma Aldosterone and Natriuretic Peptides in Atrial Fibrillation

    DEFF Research Database (Denmark)

    Dixen, Ulrik; Ravn, Lasse Steen; Soeby-Rasmussen, Christian;

    2006-01-01

    BACKGROUND AND AIMS: During atrial fibrillation (AF), the renin-angiotensin-aldosterone system (RAAS) may be activated. In this study, our aim was to evaluate at a long-term follow-up visit the levels of plasma aldosterone and natriuretic peptides as markers of neurohormonal remodeling in patients...... with earlier, documented AF in relation to present heart rhythm, clinical data, and the left ventricular ejection fraction (LVEF). We hypothesized that increased levels of aldosterone and natriuretic peptides were significantly associated with present AF as markers of RAAS activation during the arrhythmia...

  4. Raised plasma aldosterone and natriuretic peptides in atrial fibrillation

    DEFF Research Database (Denmark)

    Dixen, U; Ravn, L; Soeby-Rasmussen, C;

    2007-01-01

    During atrial fibrillation (AF), the renin-angiotensin-aldosterone system (RAAS) may be activated. In this study, our aim was to evaluate at a long-term follow-up visit the levels of plasma aldosterone and natriuretic peptides as markers of neurohormonal remodeling in patients with earlier......, documented AF in relation to present heart rhythm, clinical data, and the left ventricular ejection fraction (LVEF). We hypothesized that increased levels of aldosterone and natriuretic peptides were significantly associated with present AF as markers of RAAS activation during the arrhythmia....

  5. Mechanisms and management of hypertension in autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Rahbari-Oskoui, Frederic; Williams, Olubunmi; Chapman, Arlene

    2014-12-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease, characterized by progressive cyst growth and renal enlargement, resulting in renal failure. Hypertension is common and occurs early, prior to loss of kidney function. Whether hypertension in ADPKD is a primary vasculopathy secondary to mutations in the polycystin genes or secondary to activation of the renin-angiotensin-aldosterone system by cyst expansion and intrarenal ischemia is unclear. Dysregulation of the primary cilium causing endothelial and vascular smooth muscle cell dysfunction is a component of ADPKD. In this article, we review the epidemiology, pathophysiology and clinical characteristics of hypertension in ADPKD and give specific recommendations for its treatment.

  6. 心脑血管疾病与肾素血管紧张素醛固酮系统

    Institute of Scientific and Technical Information of China (English)

    刘晓明; 苏兰娣

    2010-01-01

    肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system,RAAS)的激活不但和多种心血管疾病如高血压、心肌肥厚、动脉粥样硬化、动脉中层硬化及心力衰竭等的发生发展关系极为密切,还可引起脑水肿的发生,加重缺血性脑组织的损害[1].

  7. Ipertensione arteriosa, continuum cardiovascolare e ruolo clinico dei sartanii

    Directory of Open Access Journals (Sweden)

    Maurizio Destro

    2011-03-01

    Full Text Available The cardiovascular and cardiorenal continuum comprises the transition from cardiovascular risk factors to endothelial dysfunction and atherosclerosis, to chronic congestive heart failure, and-stage renal disease or premature death. RAAS (renin-angiotensin-aldosterone system is involved in all steps along this pathway. Data from clinical studies involving valsartan and other ARBs provide evidence of the reduction of risk of cardiovascular events, and end-organ damage in the heart, kidneys and brain. This paper summarizes the status on research of ARBs based on clinical trials and regulatory approval.

  8. Regulatory mechanisms in arterial hypertension: role of microRNA in pathophysiology and therapy.

    Science.gov (United States)

    Klimczak, Dominika; Jazdzewski, Krystian; Kuch, Marek

    2017-02-01

    Multiple factors underlie the pathophysiology of hypertension, involving endothelial dysregulation, vascular smooth muscle dysfunction, increased oxidative stress, sympathetic nervous system activation and altered renin -angiotensin -aldosterone regulatory activity. A class of non-coding RNA called microRNA, consisting of 17-25 nucleotides, exert regulatory function over these processes. This paper summarizes the currently available data from preclinical and clinical studies on miRNA in the development of hypertension as well as the impact of anti-hypertensive treatment on their plasma expression. We present microRNAs' characteristics, their biogenesis and role in the regulation of blood pressure together with their potential diagnostic and therapeutic application in clinical practice.

  9. Pathogenetic relationship between coronary heart disease and osteopenic syndrome

    Directory of Open Access Journals (Sweden)

    N. S. Mykhailovskaya

    2015-02-01

    Full Text Available The importance of the comorbidity problem of coronary heart disease and osteoporosis is caused by the rising prevalence, lack of early detection, prevention, severe complications and significant impact on the quality of life of the patients. Aim. In order to compile and submit a current point of view on the pathogenetic relationship between the coronary heart disease and the osteopenic syndrome we reviewed specialized literature. Conclusion. We established that coronary heart disease and osteoporosis have common mechanisms of progression involving a cascade of proinflammatory cytokines, osteoprotegerin, endothelial dysfunction, estrogen, calcium deficiency, the renin-angiotensin-aldosterone and sympathetic nervous system.

  10. Renin release

    DEFF Research Database (Denmark)

    Schweda, Frank; Friis, Ulla; Wagner, Charlotte;

    2007-01-01

    The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in salt, volume, and blood pressure homeostasis of the body. Renin is mainly produced and released into circulation by the so-called juxtaglomerular epithelioid cells, located......, salt, and volume overload. In contrast, the events controlling the function of renin-secreting cells at the organ and cellular level are markedly less clear and remain mysterious in certain aspects. The unravelling of these mysteries has led to new and interesting insights into the process of renin...

  11. An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function

    DEFF Research Database (Denmark)

    Holtkamp, Frank A; de Zeeuw, Dick; Thomas, Merlin C

    2011-01-01

    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 hem......GFR, during losartan treatment, the slower the rate of long-term eGFR decline. Hence, interpretation of trial results relying on slope-based GFR outcomes should separate the initial drug-induced GFR change from the subsequent long-term effect on GFR....

  12. Characterization of a novel phosphorylation site in the sodium-chloride cotransporter, NCC

    DEFF Research Database (Denmark)

    Rosenbaek, L L; Assentoft, M; Pedersen, N B

    2012-01-01

    DAVP significantly increased pS124-NCC abundance, with no changes in total NCC plasma membrane abundance. pS124-NCC levels also increased in abundance in rats after stimulation of the renin-angiotensin-aldosterone system by dietary low sodium intake. In contrast to other NCC phosphorylation sites, the STE20/SPS1......The sodium-chloride cotransporter, NCC, is essential for renal electrolyte balance. NCC function can be modulated by protein phosphorylation. In this study, we characterized the role and physiological regulation of a novel phosphorylation site in NCC at Ser124 (S124). Novel phospho...

  13. Mechanisms of renal NaCl retention in proteinuric disease

    DEFF Research Database (Denmark)

    Svenningsen, Per; Friis, Ulla G; Versland, Jostein B

    2013-01-01

    In diseases with proteinuria, for example nephrotic syndrome and pre-eclampsia, there often are suppression of plasma renin-angiotensin-aldosterone system components, expansion of extracellular volume and avid renal sodium retention. Mechanisms of sodium retention in proteinuria are reviewed....... In animal models of nephrotic syndrome, the amiloride-sensitive epithelial sodium channel ENaC is activated while more proximal renal Na(+) transporters are down-regulated. With suppressed plasma aldosterone concentration and little change in ENaC abundance in nephrotic syndrome, the alternative modality...

  14. Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms.

    Science.gov (United States)

    Hall, John E; do Carmo, Jussara M; da Silva, Alexandre A; Wang, Zhen; Hall, Michael E

    2015-03-13

    Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65% to 75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include (1) physical compression of the kidneys by fat in and around the kidneys, (2) activation of the renin-angiotensin-aldosterone system, and (3) increased sympathetic nervous system activity. Activation of the renin-angiotensin-aldosterone system is likely due, in part, to renal compression, as well as sympathetic nervous system activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for sympathetic nervous system activation in obesity have not been fully elucidated but may require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes mellitus, and inflammation. Unless effective antiobesity drugs are developed, the effect of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase.

  15. Effect of olive oil phenolic compounds on the expression of blood pressure-related genes in healthy individuals.

    Science.gov (United States)

    Martín-Peláez, Sandra; Castañer, Olga; Konstantinidou, Valentini; Subirana, Isaac; Muñoz-Aguayo, Daniel; Blanchart, Gemma; Gaixas, Sonia; de la Torre, Rafael; Farré, Magí; Sáez, Guillermo T; Nyyssönen, Kristina; Zunft, Hans Joachim; Covas, Maria Isabel; Fitó, Montse

    2017-03-01

    To investigate whether the ingestion of olive oil having different phenolic contents influences the expression of blood pressure-related genes, involved in the renin-angiotensin-aldosterone system, in healthy humans. A randomized, double-blind, crossover human trial with 18 healthy subjects, who ingested 25 mL/day of olive oils (1) high (366 mg/kg, HPC) and (2) low (2.7 mg/kg, LPC) in phenolic compounds for 3 weeks, preceded by 2-week washout periods. Determination of selected blood pressure-related gene expression in peripheral blood mononuclear cells (PBMNC) by qPCR, blood pressure and systemic biomarkers. HPC decreased systolic blood pressure compared to pre-intervention values and to LPC, and maintained diastolic blood pressure values compared to LPC. HPC decreased ACE and NR1H2 gene expressions compared with pre-intervention values, and IL8RA gene expression compared with LPC. The introduction to the diet of an extra-virgin olive oil rich in phenolic compounds modulates the expression of some of the genes related to the renin-angiotensin-aldosterone system. These changes could underlie the decrease in systolic blood pressure observed.

  16. 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.

  17. Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension.

    Science.gov (United States)

    Giles, Thomas D; Bakris, George; Oparil, Suzanne; Weber, Michael A; Li, Huiling; Mallick, Madhuja; Bharucha, David B; Chen, ChunLin; Ferguson, William G

    2015-11-01

    After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further.

  18. The "chloride theory", a unifying hypothesis for renal handling and body fluid distribution in heart failure pathophysiology.

    Science.gov (United States)

    Kataoka, Hajime

    2017-07-01

    Body fluid volume regulation is a complex process involving the interaction of various afferent (sensory) and neurohumoral efferent (effector) mechanisms. Historically, most studies focused on the body fluid dynamics in heart failure (HF) status through control of the balance of sodium, potassium, and water in the body, and maintaining arterial circulatory integrity is central to a unifying hypothesis of body fluid regulation in HF pathophysiology. The pathophysiologic background of the biochemical determinants of vascular volume in HF status, however, has not been known. I recently demonstrated that changes in vascular and red blood cell volumes are independently associated with the serum chloride concentration, but not the serum sodium concentration, during worsening HF and its recovery. Based on these observations and the established central role of chloride in the renin-angiotensin-aldosterone system, I propose a unifying hypothesis of the "chloride theory" for HF pathophysiology, which states that changes in the serum chloride concentration are the primary determinant of changes in plasma volume and the renin-angiotensin-aldosterone system under worsening HF and therapeutic resolution of worsening HF. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition.

    Science.gov (United States)

    Hubers, Scott A; Brown, Nancy J

    2016-03-15

    Heart failure affects ≈5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the US Food and Drug Administration approved the first of a new class of drugs for the treatment of heart failure: Valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses 2 of the pathophysiological mechanisms of heart failure: activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared with enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacological properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension.

  20. Bradykinin and matrix metalloproteinases are involved the structural alterations of rat small resistance arteries with inhibition of ACE and NEP.

    Science.gov (United States)

    Rizzoni, Damiano; Rossi, Gian Paolo; Porteri, Enzo; Sticchi, Daniele; Rodella, Luigi; Rezzani, Rita; Sleiman, Intissar; De Ciuceis, Carolina; Paiardi, Silvia; Bianchi, Rossella; Nussdorfer, G G; Agabiti-Rosei, Enrico

    2004-04-01

    Increased vascular resistance is a hallmark of hypertension and involves structural alterations, which may entail smooth muscle cell hypertrophy or hyperplasia, or qualitative or quantitative changes in extracellular matrix (ECM) proteins. Since the renin-angiotensin-aldosterone system modulates these changes, we investigated the effects of 8 weeks of treatment with an angiotensin-converting enzyme (ACE) inhibitor, ramipril (RAM), or a dual ACE and neutral endopeptidase (NEP) inhibitor, MDL-100240 (MDL), on mesenteric small artery structure and ECM proteins in mRen2-transgenic rats (TGRs), an animal model of hypertension with severe cardiovascular damage. Thirty-five 5-week-old rats were included in the study: six TGRs received RAM; five TGRs RAM + the bradykinin receptor inhibitor, icatibant; six TGRs, MDL; and five TGRs MDL + icatibant, while eight TGRs and five normotensive Sprague-Dawley controls were kept untreated. Mesenteric small arteries were dissected and mounted on a micromyograph. The media-to-lumen ratio (M/L) was then calculated. Vascular metalloproteinase (MMP) content was evaluated by zymography. In untreated TGRs severe hypertension was associated with inward eutrophic remodelling of small arteries. Both RAM and MDL prevented the increase in blood pressure and M/L and decreased MMPs. Icatibant blunted the effect of MDL on BP, M/L and MMPs. Changes in collagenase activity induced by ramipril and MDL are associated with prevention of small artery structural alterations in TGRs. Furthermore, MDL-induced enhancement of bradykinin could play a role in both the prevention of vascular structural alterations and in the stimulation of MMPs.

  1. Neurohumoral blockade in CHF management

    Directory of Open Access Journals (Sweden)

    Roland Willenbrock

    2000-03-01

    Full Text Available Is heart failure an endocrine disease? Historically, congestive heart failure (CHF has often been regarded as a mechanical and haemodynamic condition. However, there is now strong evidence that the activation of neuroendocrine systems, like the renin-angiotensin-aldosterone system (RAAS and sympathetic nervous system, as well as the activation of natriuretic peptides, endothelin and vasopressin, play key roles in the progression of CHF. In this context, agents targeting neurohormones offer a highly rational approach to CHF management, with ACE inhibitors, aldosterone antagonists and beta-adrenergic blockade improving the prognosis for many patients. Although relevant improvements in clinical status and survival can be achieved with these drug classes, mortality rates for patients with CHF are still very high. Moreover, most patients do not receive these proven life-prolonging drugs, partially due to fear of adverse events, such as hypotension (with ACE inhibitors, gynaecomastia (with spironolactone and fatigue (with beta-blockers.New agents that combine efficacy with better tolerability are therefore needed. The angiotensin II type 1 (AT1-receptor blockers have the potential to fulfil both these requirements, by blocking the deleterious cardiovascular and haemodynamic effects of angiotensin II while offering placebo-like tolerability. As shown with candesartan, AT1-receptor blockers also modulate the levels of other neurohormones, including aldosterone and atrial natriuretic peptide (ANP. Combined with its tight, long-lasting binding to AT1-receptors, this characteristic gives candesartan the potential for complete blockade of the RAAS-neurohormonal axis, along with the great potential to improve clinical outcomes.

  2. Amiloride lowers blood pressure and attenuates urine plasminogen activation in patients with treatment-resistant hypertension.

    Science.gov (United States)

    Oxlund, Christina S; Buhl, Kristian B; Jacobsen, Ib A; Hansen, Mie R; Gram, Jeppe; Henriksen, Jan Erik; Schousboe, Karoline; Tarnow, Lise; Jensen, Boye L

    2014-12-01

    In conditions with albuminuria, plasminogen is aberrantly filtered across the glomerular barrier and activated along the tubular system to plasmin. In the collecting duct, plasmin activates epithelial sodium channels (ENaC) proteolytically. Hyperactivity of ENaC could link microalbuminuria/proteinuria to resistant hypertension. Amiloride, an ENaC inhibitor, inhibits urokinase-type plasminogen activator. We hypothesized that amiloride (1) reduces blood pressure (BP); (2) attenuates plasminogen-to-plasmin activation; and (3) inhibits urine urokinase-type plasminogen activator in patients with resistant hypertension and type 2 diabetes mellitus (T2DM).In an open-label, non-randomized, 8-week intervention study, a cohort (n = 80) of patients with resistant hypertension and T2DM were included. Amiloride (5 mg/d) was added to previous triple antihypertensive treatment (including a diuretic and an inhibitor of the renin-angiotensin-aldosterone system) and increased to 10 mg if BP control was not achieved at 4 weeks. Complete dataset for urine analysis was available in 60 patients. Systolic and diastolic BP measured by ambulatory BP monitoring and office monitoring were significantly reduced. Average daytime BP was reduced by 6.3/3.0 mm Hg. Seven of 80 cases (9%) discontinued amiloride due to hyperkalemia >5.5 mol/L, the most frequent adverse event. Urinary plasmin(ogen) and albumin excretions were significantly reduced after amiloride treatment (P treatment. Amiloride lowers BP, urine plasminogen excretion and activation, and albumin/creatinine ratio, and is a relevant add-on medication for the treatment of resistant hypertension in patients with T2DM and microalbuminuria.

  3. Efficacy and safety of LCI699 for hypertension: a meta-analysis of randomized controlled trials and systematic review.

    Science.gov (United States)

    Wang, H-Z; Tian, J-B; Yang, K H

    2015-01-01

    This study reviews the available data from randomized controlled trials on efficacy and safety of LCI699, a novel inhibitor of aldosterone synthase, as treatment of hypertension. We performed a meta-analysis of phase II randomized, controlled trials comparing the efficacy/safety of LCI699 with placebo in hypertension patients. For this purpose, PubMed, Embase, Cochrane Library database, ISI-Science Citation Index, and the Chinese Biomedicine Literature Database were searched until August 2013. The available data on mean sitting systolic blood pressure (MSSBP), mean sitting diastolic blood pressure (MSDBP), adverse effects, renin-angiotensin-aldosterone system biomarkers (RAASB) and adrenocorticotropic hormone-stimulated cortisol concentration (AHSC) were collected. All data were analyzed using Review Manager, version 5.2. The present study finally included three randomized controlled trials, comprising of 623 patients in total. The daily use of ≥ 1 mg LCI699 was associated with a significant reduction of MSSBP (Weighted mean difference/WMD = -8.80, 95% CI: -11.31 to -5.68, p risk of side effects compared with placebo (RR = 0.90; 95% CI: 0.68 to 1.18, p = 0.43, I2 = 0%). Suppression of plasma aldosterone was measured at all doses of LCI699 treatment groups. LCI699 suppressed the ACTH-stimulated cortisol response in a dose- and time-dependent manner. Current evidence indicates that the novel aldosterone inhibitor LCI699 is an effective and well-tolerated antihypertensive agent that lowers plasma aldosterone concentration and produces a mild ACTH-stimulated cortisol response suppressive effect.

  4. Role of O-linked N-acetylglucosamine modification in diabetic nephropathy.

    Science.gov (United States)

    Gellai, Renata; Hodrea, Judit; Lenart, Lilla; Hosszu, Adam; Koszegi, Sandor; Balogh, Dora; Ver, Agota; Banki, Nora F; Fulop, Norbert; Molnar, Agnes; Wagner, Laszlo; Vannay, Adam; Szabo, Attila J; Fekete, Andrea

    2016-12-01

    Increased O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) is a known contributor to diabetes; however, its relevance in diabetic nephropathy (DN) is poorly elucidated. Here, we studied the process and enzymes of O-GlcNAcylation with a special emphasis on Akt-endothelial nitric oxide synthase (eNOS) and heat shock protein (HSP)72 signaling. Since tubular injury is the prominent site of DN, the effect of hyperglycemia was first measured in proximal tubular (HK2) cells cultured in high glucose. In vivo O-GlcNAcylation and protein levels of O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), phosphorylated (p)Akt/Akt, peNOS/eNOS, and HSP72 were assessed in the kidney cortex of streptozotocin-induced diabetic rats. The effects of various renin-angiotensin-aldosterone system (RAAS) inhibitors were also evaluated. In proximal tubular cells, hyperglycemia-induced OGT expression led to increased O-GlcNAcylation, which was followed by a compensatory increase of OGA. In parallel, peNOS and pAkt levels decreased, whereas HSP72 increased. In diabetic rats, elevated O-GlcNAcylation was accompanied by decreased OGT and OGA. RAAS inhibitors ameliorated diabetes-induced kidney damage and prevented the elevation of O-GlcNAcylation and the decrement of pAkt, peNOS, and HSP72. In conclusion, hyperglycemia-induced elevation of O-GlcNAcylation contributes to the progression of DN via inhibition of Akt/eNOS phosphorylation and HSP72 induction. RAAS blockers successfully inhibit this process, suggesting a novel pathomechanism of their renoprotective action in the treatment of DN.

  5. Corrosion inhibitors for intermediate cooling systems

    Energy Technology Data Exchange (ETDEWEB)

    Falk, I.; Suhr, L.

    1985-04-01

    The selected inhibitors were tested for heat and radiation stability and corrosion protection on the bench scale. Based on the results from these tests two of the products were selected, Bycoguard 81 and Bycoguard MP4S for continuing corrosion tests in an autoclave loop at 90 degrees C and 120 degrees C. Oxygen saturated deionized water with an addition of 1 ppm chloride was recirculated in the loop. Samples of copper and carbon steel were exposed to the water in the autoclave for periods up to 10 weeks. The purpose of this project was to find a substitute for hydrazine and chromates. Besides good corrosion protection qualities the toxic and environmental effect of the inhibitors should be minimal. The investigation has shown that the copper inhibitor BTA (benzotriazole) loses its corrosion protection qualities at a water temperature of 120 degrees C. The protection effects at 90 degrees C were satisfactory for both of the materials. The corrosion rates measured were 0.01 mm/y or less for the copper and carbon steel samples. The environment in the autoclave during the testing was more corrosive than is to be found in intermediate cooling systems. Due to the low corrosion rates measured the two inhibitors are to be recommended as alternatives to hydrazine and chromates.

  6. Should we prescribe blood pressure lowering drugs to every patient with advanced chronic kidney disease? A comment on two recent meta-analyses.

    Science.gov (United States)

    Gross, Peter; Schirutschke, Holger; Barnett, Kerstin

    2009-10-01

    Antihypertensive treatment is an essential, life-prolonging measure in primary hypertension. It prevents apoplexy, myocardial infarction, and hypertensive kidney failure. Chronic kidney failure is associated with hypertension and an accelerated form of arteriosclerosis. Demise from cardiovascular affliction is a leading cause of death in renal patients (chronic renal failure stages II-IV, renal failure requiring dialysis, renal transplantation). What, then, is the role of antihypertensive treatment in such patients, and, specifically, what is achieved by renin-angiotensin-aldosterone (RAA) system modifying agents? Two meta-analyses have recently investigated these issues. An article in The Lancet evaluated eight studies on dialysis patients (n = 1679). It concluded that antihypertensives are beneficial in reducing cardiovascular morbidity and mortality. However, we criticize these conclusions and show that the data are not convincingly in favor of antihypertensive treatment. A meta-analysis in the American Heart Journal assessed the role of antihypertensive agents and RAA system modifying drugs in 45,758 patients (from 25 studies), who were in stages I-III of renal failure, i.e., not (yet) requiring dialysis. The authors claim that angiotensin- -converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) significantly reduced cardiovascular outcomes. However, our analysis of the data is not consistent with their conclusions. It showed that the results were quite mixed, that the authors may have overemphasized the positive results, and that considering all the results, it should be concluded that antihypertensive treatments, including those with ACEI/ARB, may not be superior to placebo (sic!) in renal patients. Rather than doing meta-analyses, larger primary studies are needed to reveal the real role of antihypertensive treatments in renal patients.

  7. ACEI attenuates the progression of CCl4-induced rat hepatic fibrogenesis by inhibiting TGF-β1, PDGF-BB, NF-κB and MMP-2,9

    Institute of Scientific and Technical Information of China (English)

    Xu Li; Ying Meng; Xi-Shan Yang; Ling-Fei Mi; Shao-Xi Cai

    2005-01-01

    AIM: Angiotensin Ⅱ has pro-fibrotic function in the liver.Blockade of the renin-angiotensin-aldosterone-system (RAAS) attenuates hepatic fibrosis. The aim of the present study was to determine the mechanism of angiotensinconverting enzyme inhibitor (ACEI) on the progression of rat hepatic fibrosis.METHODS: Forty male Wistar rats were divided into three groups. Model group (Mo): The rats were injected subcutaneously with 40% of CCl4 0.25 mL/100 g. Perindopril group (Pe): The rats were injected subcutaneously with administrated. Control group (Nc): the rats were treated with olive oil only. After 4 and 6 wk, the rats were killed.The liver sections were stained with Masson. The protein expressions of AT1R, TGF-β1 and PDGF-BB were examined by Western blot. Nuclear factor κB (NF-κB) DNA binding activity was examined by EMSA (Electrophoretic gel mobility shift assay). Matrix metalloproteinase-2,9(MMP-2,9) activity was assessed by zymography. Serum laminin (LN) and hyaluronic acid (HA) were measured using radioimmunoassays.RESULTS: Using Western blot, we clearly provided direct evidence for the expression of AT1R in liver. The expression was up-regulated when fibrogenesis occurred. Perindopril treatment significantly reduced mean fibrosis score,protein levels of AT1R, TGF-β1 and PDGF-BB, serum levels of HA and LN, and the activity of MMP-2,9. NF-κB DNA binding activity markedly increased in model group, perindopril treatment considerably reduced NF-κB DNA binding activity.CONCLUSION: Perindopril attenuates CCl4-induced hepatic fibrogenesis of rat by inhibiting TGF-β1, PDGF-BB,NF-κB and MMP-2,9.

  8. Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring.

    Science.gov (United States)

    Xue, Baojian; Yin, Haifeng; Guo, Fang; Beltz, Terry G; Thunhorst, Robert L; Johnson, Alan Kim

    2017-04-01

    Numerous findings demonstrate that there is a strong association between maternal health during pregnancy and cardiovascular disease in adult offspring. The purpose of the present study was to test whether maternal gestational hypertension modulates brain renin-angiotensin-aldosterone system (RAAS) and proinflammatory cytokines that sensitizes angiotensin II-elicited hypertensive response in adult offspring. In addition, the role of renal nerves and the RAAS in the sensitization process was investigated. Reverse transcription polymerase chain reaction analyses of structures of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAAS components and proinflammatory cytokines in 10-week-old male offspring of hypertensive dams. Most of these increases were significantly inhibited by either renal denervation performed at 8 weeks of age or treatment with an angiotensin-converting enzyme inhibitor, captopril, in drinking water starting at weaning. When tested beginning at 10 weeks of age, a pressor dose of angiotensin II resulted in enhanced upregulation of mRNA expression of RAAS components and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented pressor response in male offspring of hypertensive dams. The augmented blood pressure change and most of the increases in gene expression in the offspring were abolished by either renal denervation or captopril. The results suggest that maternal hypertension during pregnancy enhances pressor responses to angiotensin II through overactivity of renal nerves and the RAAS in male offspring and that upregulation of the brain RAAS and proinflammatory cytokines in these offspring may contribute to maternal gestational hypertension-induced sensitization of the hypertensive response to angiotensin II. © 2017 American Heart Association, Inc.

  9. Serum aldosterone and death, end-stage renal disease, and cardiovascular events in blacks and whites: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

    Science.gov (United States)

    Deo, Rajat; Yang, Wei; Khan, Abigail M; Bansal, Nisha; Zhang, Xiaoming; Leonard, Mary B; Keane, Martin G; Soliman, Elsayed Z; Steigerwalt, Susan; Townsend, Raymond R; Shlipak, Michael G; Feldman, Harold I

    2014-07-01

    Prior studies have demonstrated that elevated aldosterone concentrations are an independent risk factor for death in patients with cardiovascular disease. Limited studies, however, have evaluated systematically the association between serum aldosterone and adverse events in the setting of chronic kidney disease. We investigated the association between serum aldosterone and death and end-stage renal disease in 3866 participants from the Chronic Renal Insufficiency Cohort. We also evaluated the association between aldosterone and incident congestive heart failure and atherosclerotic events in participants without baseline cardiovascular disease. Cox proportional hazards models were used to evaluate independent associations between elevated aldosterone concentrations and each outcome. Interactions were hypothesized and explored between aldosterone and sex, race, and the use of loop diuretics and renin-angiotensin-aldosterone system inhibitors. During a median follow-up period of 5.4 years, 587 participants died, 743 developed end-stage renal disease, 187 developed congestive heart failure, and 177 experienced an atherosclerotic event. Aldosterone concentrations (per SD of the log-transformed aldosterone) were not an independent risk factor for death (adjusted hazard ratio, 1.00; 95% confidence interval, 0.93-1.12), end-stage renal disease (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99-1.17), or atherosclerotic events (adjusted hazard ratio, 1.04; 95% confidence interval, 0.85-1.18). Aldosterone was associated with congestive heart failure (adjusted hazard ratio, 1.21; 95% confidence interval, 1.02-1.35). Among participants with chronic kidney disease, higher aldosterone concentrations were independently associated with the development of congestive heart failure but not for death, end-stage renal disease, or atherosclerotic events. Further studies should evaluate whether mineralocorticoid receptor antagonists may reduce adverse events in individuals with

  10. Urinary heparanase activity in patients with Type 1 and Type 2 diabetes.

    Science.gov (United States)

    Rops, Angelique L W M M; van den Hoven, Mabel J; Veldman, Bart A; Salemink, Simone; Vervoort, Gerald; Elving, Lammy D; Aten, Jan; Wetzels, Jack F; van der Vlag, Johan; Berden, Jo H M

    2012-07-01

    A reduced heparan sulphate (HS) expression in the glomerular basement membrane of patients with overt diabetic nephropathy is associated with an increased glomerular heparanase expression. We investigated the possible association of urinary heparanase activity with the development of proteinuria in patients with Type 1 diabetes (T1D), Type 2 diabetes (T2D), or membranous glomerulopathy (MGP) as non-diabetic disease controls. Heparanase activity, albumin, HS and creatinine were measured in the urine of patients with T1D (n=58) or T2D (n=31), in patients with MGP (n=52) and in healthy controls (n=10). Heparanase messenger RNA (mRNA) expression in leukocytes was determined in a subgroup of patients with T1D (n=19). Urinary heparanase activity was increased in patients with T1D and T2D, which was more prominent in patients with macroalbuminuria, whereas no activity could be detected in healthy controls. Albuminuria levels were associated with increased urinary heparanase activity in diabetic patients (r=0.20; P<0.05) but not in patients with MGP (r=0.11; P=0.43). A lower urinary heparanase activity was observed in diabetic patients treated with inhibitors of the renin-angiotensin-aldosterone system (RAAS), when compared to diabetic patients treated with other anti-hypertensives. Additionally, urinary heparanase activity was associated with age in T1D and MGP. In MGP, heparanase activity and β2-microglobulin excretion correlated. In patients with T1D, no differences in heparanase mRNA expression in leukocytes could be observed. Urinary heparanase activity is increased in diabetic patients with proteinuria. However, whether increased heparanase activity is a cause or consequence of proteinuria requires additional research.

  11. CHRONIC HEART FAILURE: CLINICAL GUIDELINES AND REAL CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    E. K. Shavarova

    2016-01-01

    Full Text Available Aim. Expert assessment of real clinical practice compliance with national guidelines on management of patients with chronic heart failure (HF before the opening of the Expert Center of HF treatment.Material and methods. All patients admitted to 2 city clinical hospitals of Moscow with HF were included into the register. Clinical, demographic, laboratory and instrumental characteristics and medical treatment before and during hospitalization were evaluated, as well as recommendations contained in the discharge summary.Results. 300 patients with HF were included into the register. The mean age was 75 years (39, 95; the proportion of men – 44%. 95% of patients had HF IIIV (NYHA, among them 24% HF II, 61% HF III, 15% HF IV (NYHA. HF with reduced ejection fraction (HFrEF was found in 45% of patients. 22% of the patients did not receive medical treatment before admission. 34% of patients with HFrEF received ACE inhibitors/angiotensin receptor blockers (ARBs, of which only 23% in effective dose. β-blockers were prescribed in 41% of HFeEF patients, of which 22% in the target dose. A third of patients needed in mineralocorticoid receptor antagonists (MRA received spironolactone. During hospitalization 81% of HFrEF patients received ACEI therapy, 12% – ARBs, 91% – β-blockers, 90% – MRA, 81% – loop diuretics and 13% – thiazide diuretics. According to the discharge summary 5% of patients did not receive post-discharge blocker of the renin-angiotensin-aldosterone system without explanation in the medical documentation. β-blocker with proven efficacy was prescribed to 70% of HFrEF patients. Spironolactone was recommended after discharge in 89% of HFrEF patients.Conclusion. Implementation of register of hospitalized patients with HF gives an opportunity to identify shortcomings in the provision of medical care both in outpatient and inpatient stages. 

  12. Baseline characteristics in the Bardoxolone methyl EvAluation in patients with Chronic kidney disease and type 2 diabetes mellitus: the Occurrence of renal eveNts (BEACON) trial.

    Science.gov (United States)

    Lambers Heerspink, Hiddo J; Chertow, Glenn M; Akizawa, Tadao; Audhya, Paul; Bakris, George L; Goldsberry, Angie; Krauth, Melissa; Linde, Peter; McMurray, John J; Meyer, Colin J; Parving, Hans-Henrik; Remuzzi, Giuseppe; Christ-Schmidt, Heidi; Toto, Robert D; Vaziri, Nosratola D; Wanner, Christoph; Wittes, Janet; Wrolstad, Danielle; de Zeeuw, Dick

    2013-11-01

    Type 2 diabetes mellitus (T2DM) is the most important contributing cause of end-stage renal disease (ESRD) worldwide. Bardoxolone methyl, a nuclear factor-erythroid-2-related factor 2 activator, augments estimated glomerular filtration. The Bardoxolone methyl EvAluation in patients with Chronic kidney disease and type 2 diabetes mellitus: the Occurrence of renal eveNts (BEACON) trial was designed to establish whether bardoxolone methyl slows or prevents progression to ESRD. Herein, we describe baseline characteristics of the BEACON population. BEACON is a randomized double-blind placebo-controlled clinical trial in 2185 patients with T2DM and chronic kidney disease stage 4 (eGFR between 15 and 30 mL/min/1.73 m(2)) designed to test the hypothesis that bardoxolone methyl added to guideline-recommended treatment including inhibitors of the renin-angiotensin-aldosterone system slows or prevents progression to ESRD or cardiovascular death compared with placebo. Baseline characteristics (mean or percentage) of the population include age 68.5 years, female 43%, Caucasian 78%, eGFR 22.5 mL/min/1.73 m(2) and systolic/diastolic blood pressure 140/70 mmHg. The median urinary albumin:creatinine ratio was 320 mg/g and the frequency of micro- and macroalbuminuria was 30 and 51%, respectively. Anemia, abnormalities in markers of bone metabolism and elevations in cardiovascular biomarkers were frequently observed. A history of cardiovascular disease was present in 56%, neuropathy in 47% and retinopathy in 41% of patients. The BEACON trial enrolled a population heretofore unstudied in an international randomized controlled trial. Enrolled patients suffered with numerous co-morbid conditions and exhibited multiple laboratory abnormalities, highlighting the critical need for new therapies to optimize management of these conditions.

  13. Alport Syndrome in Women and Girls.

    Science.gov (United States)

    Savige, Judy; Colville, Deb; Rheault, Michelle; Gear, Susie; Lennon, Rachel; Lagas, Sharon; Finlay, Moira; Flinter, Frances

    2016-09-07

    Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Inheritance is X-linked (85%) or autosomal recessive (15%). Many renal physicians think of Alport syndrome as primarily affecting men. However, twice as many women are affected by the X-linked diseases. Affected women are commonly undiagnosed, but 15%-30% develop renal failure by 60 years and often hearing loss by middle age. Half of their sons and daughters are also affected. Autosomal recessive Alport syndrome is less common, but is often mistaken for X-linked disease. Recessive inheritance is suspected where women develop early-onset renal failure or lenticonus. Their family may be consanguineous. The prognosis for other family members is very different from X-linked disease. Other generations, including parents and offspring, are not affected, and on average only one in four of their siblings inherit the disease. All women with Alport syndrome should have their diagnosis confirmed with genetic testing, even if their renal function is normal, because of their own risk of renal failure and the risk to their offspring. Their mutations indicate the mode of inheritance and the likelihood of disease transmission to their children, and the mutation type suggests the renal prognosis for both X-linked and recessive disease. Women with X-linked Alport syndrome should be tested at least annually for albuminuria and hypertension. The "Expert guidelines for the diagnosis and management of Alport syndrome" recommend treating those with albuminuria with renin-angiotensin-aldosterone system (RAAS) blockade (and adequate birth control because of the teratogenic risks of angiotensin converting enzyme inhibitors), believing that this will delay renal failure. Current recommendations are that women with autosomal recessive Alport syndrome should be treated with RAAS blockade from the time of diagnosis. In addition, women should be offered genetic counseling

  14. Preventing type 2 diabetes mellitus: room for residual risk reduction after lifestyle changes?

    Science.gov (United States)

    Athyros, Vasilios G; Tziomalos, Konstantinos; Karagiannis, Asterios; Mikhailidis, Dimitri P

    2010-01-01

    It is well known that type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular diseases (CVD). A predicted worldwide increase in the incidence of T2DM, taking the form of an epidemic, is expected to induce a substantial increase in CVD incidence. Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are related to an increased risk of developing T2DM, especially in obese people. Prevention of T2DM aiming to reversal of pre-diabetes to normal glucose tolerance seems to be a very attractive target, and favourably affects CVD risk factors. The Diabetes Prevention Program and the Finnish Diabetes Prevention studies showed that changes in lifestyle prevented or delayed the onset of new cases of T2DM in subjects with pre-diabetes by 58%. However, a fraction of participants still developed T2DM, suggesting a residual risk. Moreover, lifestyle changes are not usually followed on a long-term basis as shown in EUROASPIRE with an increase in new onset T2DM by 60% in subjects with CVD in just over a decade. T2DM is characterized by insulin resistance and/or β-cell dysfunction (impaired insulin secretion). Various interventions targeting those two mechanisms (e.g. metformin, thiazolidinediones, acarbose, orlistate, bariatric surgery, renin-angiotensin-aldosterone system axis inhibitors, fibrates, incretin mimetics or enhancers) can prevent or delay T2DM. Widespread application of these measures has, however, been limited by financial considerations, even though cost-effectiveness might be achieved at the population level. This review will investigate feasibility and usefulness of T2DM prevention, further to that achieved with lifestyle changes, in a cost-effective manner.

  15. Effect of treatment with candesartan or enalapril on subcutaneous small artery structure in hypertensive patients with noninsulin-dependent diabetes mellitus.

    Science.gov (United States)

    Rizzoni, Damiano; Porteri, Enzo; De Ciuceis, Carolina; Sleiman, Intissar; Rodella, Luigi; Rezzani, Rita; Paiardi, Silvia; Bianchi, Rossella; Ruggeri, Giuseppina; Boari, Gianluca E M; Muiesan, Maria Lorenza; Salvetti, Massimo; Zani, Francesca; Miclini, Marco; Rosei, Enrico Agabiti

    2005-04-01

    Structural alterations of subcutaneous small resistance arteries are associated with a worse clinical prognosis in hypertension and noninsulin-dependent diabetes mellitus (NIDDM). However, no data are presently available about the effects of antihypertensive therapy on vascular structure in hypertensive patients with NIDDM. Therefore, we have investigated the effect of an angiotensin-converting enzyme inhibitor, enalapril, and a highly selective angiotensin receptor blocker, candesartan cilexetil, on indices of subcutaneous small resistance artery structure in 15 patients with mild hypertension and NIDDM. Eight patients were treated with candesartan (8 to 16 mg per day) and 7 with enalapril (10 to 20 mg per day) for 1 year. Each patient underwent a biopsy of the subcutaneous fat from the gluteal region at baseline and after 1 year of treatment. Small arteries were dissected and mounted on a micromyograph and the media-to-internal lumen ratio was evaluated; moreover, endothelium-dependent vasodilation to acetylcholine was assessed. A similar blood pressure-lowering effect and a similar reduction of the media-to-lumen ratio of small arteries was observed with the 2 drugs. Vascular collagen content was reduced and metalloproteinase-9 was increased by candesartan, but not by enalapril. Changes of circulating indices of collagen turnover and circulating matrix metalloproteinase paralleled those of vascular collagen. The 2 drugs equally improved endothelial function. In conclusion, antihypertensive treatment with drugs that inhibit the renin-angiotensin-aldosterone system activity is able to correct, at least in part, alterations in small resistance artery structure in hypertensive patients with NIDDM. Candesartan may be more effective than enalapril in reducing collagen content in the vasculature.

  16. Association of dietary sodium intake with atherogenesis in experimental diabetes and with cardiovascular disease in patients with Type 1 diabetes.

    Science.gov (United States)

    Tikellis, Chris; Pickering, Raelene J; Tsorotes, Despina; Harjutsalo, Valma; Thorn, Lena; Ahola, Aila; Wadén, Johan; Tolonen, Nina; Saraheimo, Markku; Gordin, Daniel; Forsblom, Carol; Groop, Per-Henrik; Cooper, Mark E; Moran, John; Thomas, Merlin C

    2013-05-01

    It is recommended that individuals with diabetes restrict their dietary sodium intake. However, although salt intake is correlated with BP (blood pressure), it also partly determines the activation state of the RAAS (renin-angiotensin-aldosterone system), a key mediator of diabetes-associated atherosclerosis. apoE KO (apolipoprotein E knockout) mice were allocated for the induction of diabetes with streptozotocin or citrate buffer (controls) and further randomized to isocaloric diets containing 0.05%, 0.3% or 3.1% sodium with or without the ACEi [ACE (angiotensin-converting enzyme) inhibitor] perindopril. After 6 weeks of study, plaque accumulation was quantified and markers of atherogenesis were assessed using RT-PCR (reverse transcription-PCR) and ELISA. The association of sodium intake and adverse cardiovascular and mortality outcomes were explored in 2648 adults with Type 1 diabetes without prior CVD (cardiovascular disease) from the FinnDiane study. A 0.05% sodium diet was associated with increased plaque accumulation in diabetic apoE KO mice, associated with activation of the RAAS. By contrast, a diet containing 3.1% sodium suppressed atherogenesis associated with suppression of the RAAS, with an efficacy comparable with ACE inhibition. In adults with Type 1 diabetes, low sodium intake was also associated with an increased risk of all-cause mortality and new-onset cardiovascular events. However, high sodium intake was also associated with adverse outcomes, leading to a J-shaped relationship overall. Although BP lowering is an important goal for the management of diabetes, off-target actions to activate the RAAS may contribute to an observed lack of protection from cardiovascular complications in patients with Type 1 diabetes with low sodium intake.

  17. Dietary sodium intake regulates angiotensin II type 1, mineralocorticoid receptor, and associated signaling proteins in heart.

    Science.gov (United States)

    Ricchiuti, Vincent; Lapointe, Nathalie; Pojoga, Luminita; Yao, Tham; Tran, Loc; Williams, Gordon H; Adler, Gail K

    2011-10-01

    Liberal or high-sodium (HS) intake, in conjunction with an activated renin-angiotensin-aldosterone system, increases cardiovascular (CV) damage. We tested the hypothesis that sodium intake regulates the type 1 angiotensin II receptor (AT(1)R), mineralocorticoid receptor (MR), and associated signaling pathways in heart tissue from healthy rodents. HS (1.6% Na(+)) and low-sodium (LS; 0.02% Na(+)) rat chow was fed to male healthy Wistar rats (n=7 animals per group). Protein levels were assessed by western blot and immunoprecipitation analysis. Fractionation studies showed that MR, AT(1)R, caveolin-3 (CAV-3), and CAV-1 were located in both cytoplasmic and membrane fractions. In healthy rats, consumption of an LS versus a HS diet led to decreased cardiac levels of AT(1)R and MR. Decreased sodium intake was also associated with decreased cardiac levels of CAV-1 and CAV-3, decreased immunoprecipitation of AT(1)R-CAV-3 and MR-CAV-3 complexes, but increased immunoprecipitation of AT(1)R/MR complexes. Furthermore, decreased sodium intake was associated with decreased cardiac extracellular signal-regulated kinase (ERK), phosphorylated ERK (pERK), and pERK/ERK ratio; increased cardiac striatin; decreased endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (peNOS), but increased peNOS/eNOS ratio; and decreased cardiac plasminogen activator inhibitor-1. Dietary sodium restriction has beneficial effects on the cardiac expression of factors associated with CV injury. These changes may play a role in the cardioprotective effects of dietary sodium restriction.

  18. RIESGO DE ARRITMIAS E HIPERTENSIÓN ARTERIAL / Risk of Arrhythmias and hypertension

    Directory of Open Access Journals (Sweden)

    Raimundo Carmona Puerta

    2012-03-01

    the development of arrhythmias in hypertensive patients. The presence of ventricular arrhythmias, from premature ventricular complexes to ventricular tachycardia, has been shown in a 10 to 27% of affected patients, a percentage that decreases with the severity of the arrhythmia. Noninvasive risk markers for ventricular arrhythmias have been summarized as follows: dispersion and variability of the QT interval, presence of late potentials, heart rate variability, abnormal morphology and T-wave alternans. All of these are related to anatomic-structural changes of the ventricular wall, which affect the action potential. The importance of knowing the epidemiology, pathophysiology, and noninvasive risk markers for arrhythmias in hypertensive patients, offers a way for the application of the proper therapeutic in the control of blood pressure and regression of hypertrophy, as has been shown by inhibitor drugs of the renin-angiotensin-aldosterone system, which decrease the risk of arrhythmias.

  19. Corrosion inhibitor for aqueous ammonia absorption system

    Science.gov (United States)

    Phillips, Benjamin A.; Whitlow, Eugene P.

    1998-09-22

    A method of inhibiting corrosion and the formation of hydrogen and thus improving absorption in an ammonia/water absorption refrigeration, air conditioning or heat pump system by maintaining the hydroxyl ion concentration of the aqueous ammonia working fluid within a selected range under anaerobic conditions at temperatures up to 425.degree. F. This hydroxyl ion concentration is maintained by introducing to the aqueous ammonia working fluid an inhibitor in an amount effective to produce a hydroxyl ion concentration corresponding to a normality of the inhibitor relative to the water content ranging from about 0.015 N to about 0.2 N at 25.degree. C. Also, working fluids for inhibiting the corrosion of carbon steel and resulting hydrogen formation and improving absorption in an ammonia/water absorption system under anaerobic conditions at up to 425.degree. F. The working fluids may be aqueous solutions of ammonia and a strong base or aqueous solutions of ammonia, a strong base, and a specified buffer.

  20. Changes of reni-angiotensin system and β2-microglobulin during lanaroscopic gynecology surgery under eoudyrak abesthesia%硬膜外麻醉下妇科腹腔镜手术血浆肾素-血管紧张素系统和β2微球蛋白含量的变化

    Institute of Scientific and Technical Information of China (English)

    吴进泽; 金烈烈; 张吟雪

    2001-01-01

    Objective To investigate the changes of renin-angiotensin-aldosterone system (RAAS) and glomerular filtration rate (GFR) in epidurally-anesthetized patients undergoing gynecological laparoscopy with 15° head-down position and low insufflation pressure. Methods Twenty gynecological patients(ASA grade I- Ⅱ )were studied during CO2 insufflation with an intra-abdominal pressure of 1012mmHg and 15° head-down position. Arterial blood samples were obtained for the measurements of serum concentrations of plasma renin activity(PRA), angiotensin Ⅱ (All), aldosterone(ALD) and β2-microglobulin(β2-MG)by radioimmunoassay at the following five time points: before insufflation, at 10min, 30min and 60 min after insufflation respectively and after desufflation. Arterial blood gas analysis was made in 10 of the cases simultaneously. Results Compared with preinsufflation, there was no significant decrease in the plasma levels of PRA, All ,ALD and β2-MG during CO2 pneumoperitoneum except for PRA at 10 min after insufflation(P <0.05). As the time of insufflation went on, the measurements above showed a tendency of slightly increase. The PaCO2 during peritoneal CO2 insufflation was increeseing ( P > 0.05) and reached its maximum at 30 min after insufflation. The pH values of 30~60 min after insufflation were significantly decreased as compared with that of before insufflation. Conclusion The epidural anesthesia may inhibit the response of RAAS to (CO2 insufflation pressure of 10-12mmHg and has no effect on GFR during gynecological laParoscopy.%目的观察硬膜外麻醉下,妇科腹腔镜手术患者在低CO2气腹压和15.头低脚高体位时肾素-血管紧张素系统(RAAS)和肾小球滤过率(GFR)的变化。方法监测20例患者气腹前、腹内压达1.33~1.59kPa后10、30、60分钟及解除气腹后10分钟五个时点血浆肾素(PRA)、血管紧张素Ⅱ(AⅡ)、醛固酮(ALD))和β2微球蛋白(β2-MG)的含量。其中10例患者在相应五个时点

  1. Liver cirrhosis and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2006-01-01

    blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development...... of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most......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...

  2. Endothelins in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, S; Henriksen, Jens Henrik Sahl

    1996-01-01

    renal failure. Studies on liver biopsies have revealed synthesis of ET-1 in hepatic endothelial and other cells, and recent investigations have identified the hepatosplanchnic system as a major source of ET-1 and ET-3 spillover into the circulation, with a direct relation to portal venous hypertension....... In addition, marked associations with disturbance of systemic haemodynamics and with abnormal distribution of blood volume have been reported. Although the pathophysiological importance of the ET system in chronic liver disease is not completely understood, similarities to other vasopressive...... and antinatriuretic regulatory systems (i.e. the sympathetic nervous system, renin-angiotensin-aldosterone and vasopressin) are apparent, with respect to kinetics and haemodynamic dysregulation. Cirrhosis seems to be a pathophysiological condition with indications of the occurrence of ETs, not only as local...

  3. Haemodynamics and fluid retention in liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    1998-01-01

    Patients with cirrhosis and portal hypertension exhibit characteristic haemodynamic changes with a hyperkinetic systemic circulation, an abnormal distribution of the blood volume and neurohumoral dysregulation. Their plasma and noncentral blood volumes are increased, but the central and arterial...... blood volume and systemic vascular resistance are decreased. A systemic and splanchnic vasodilatation is of pathogenic importance to the low systemic vascular resistance and abnormal volume distribution. These are important elements in the development of the low arterial blood pressure and hyperkinetic...... circulation in cirrhosis. Various vasodilators such as nitric oxide, calcitonin gene-related peptide, and adrenomedullin are among potential candidates in the vasodilatation in cirrhosis. Besides reflex induced enhanced sympathetic nervous activity, activation of the renin-angiotensin-aldosterone system...

  4. Obesity-Related Hypertension: Focus on Leptin

    DEFF Research Database (Denmark)

    Asferg, Camilla Lundegaard

    suggested to play a role in obesity-related hypertension such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, inflammation, insulin resistance, physical inactivity, and abnormal production of adipocytokines. Of all adipocytokines, leptin and adiponectin have received most...... attention and both hormones are considered as candidate intermediaries between adipose tissue and overweight and obesity-related disorders. Objectives: To study obesity-related hypertension with special focus on the hormone leptin. As obesity-related hypertension is multifactorial, other biological systems...... proposed to play a major role were also studied. Primary hypotheses: 1. leptin is a significant mediator of overweight- and obesity-related hypertension. 2. by investigating several biological systems involved in blood pressure regulation, it would be possible to identify specific factors which would...

  5. The evolution of natriuretic peptide augmentation in management of heart failure and the role of sacubitril/valsartan.

    Science.gov (United States)

    Yandrapalli, Srikanth; Aronow, Wilbert S; Mondal, Pratik; Chabbott, David R

    2017-08-01

    Heart failure (HF) is one of the leading causes of morbidity, mortality, and health care expenditures in the US and worldwide. For three decades, the pillars of treatment of HF with reduced ejection fraction (HFrEF) were medications that targeted the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Prior attempts to augment the natriuretic peptide system (NPS) for the management of HF failed either due to lack of significant clinical benefit or due to the unacceptable side effect profile. This review article will discuss the NPS, the failure of early drugs which targeted the NPS as therapies for HF, and the sequence of events which led to the development of sacubitril plus valsartan (Entresto; LCZ696; Novartis). LCZ696 has been shown to be superior to the standard of care available for treatment of HFrEF in several substantial hard endpoints including heart failure hospitalizations, cardiovascular mortality, and all-cause mortality.

  6. Vitamin D and its effects on cardiovascular diseases: a comprehensive review.

    Science.gov (United States)

    Pérez-Hernández, Nonanzit; Aptilon-Duque, Gad; Nostroza-Hernández, María Cristina; Vargas-Alarcón, Gilberto; Rodríguez-Pérez, José Manuel; Blachman-Braun, Ruben

    2016-11-01

    Vitamin D is a molecule that is actively involved in multiple metabolic pathways. It is mostly known for its implications related to calcium metabolism. It has also been determined that it actively participates in the cardiovascular system, influencing blood pressure, coronary artery disease and other vascular diseases, such as heart failure and atrial fibrillation. Furthermore, it has been established that this vitamin is extensively involved in the regulation of both the renin angiotensin aldosterone system and the immune system. In this review, we present the different vitamin D metabolic pathways associated with the cardiovascular pathophysiology, and we include studies in animal and human models, as well as some of the controversies found in the literature. This review also incorporates an overview of the implications in the molecular biology and public health fields.

  7. Vitamin D and cardiovascular disease will it live up to its hype?

    Science.gov (United States)

    Lavie, Carl J; Lee, John H; Milani, Richard V

    2011-10-04

    Substantial evidence suggests that a large portion of the population have suboptimal levels of vitamin D, which may adversely affect the cardiovascular (CV) system, including increasing levels of parathyroid hormone, activating the renin-angiotensin-aldosterone system, and increasing insulin resistance, thus leading to hypertension and left ventricular hypertrophy, metabolic syndrome/diabetes mellitus, systemic inflammation, and increased risk of atherosclerosis and CV disease events. We review the evidence that vitamin D deficiency is associated with incident CV disease events, as well as evidence that vitamin D supplementation is associated with reduction in CV diseases. Although the current evidence has created substantial hype, randomized controlled trials are needed to determine whether routine vitamin D assessment and supplementation will improve CV outcomes.

  8. Impact of obesity on kidney function and blood pressure in children.

    Science.gov (United States)

    Ding, Wei; Cheung, Wai W; Mak, Robert H

    2015-05-06

    In recent years, obesity has become an increasingly important epidemic health problem in children and adolescents. The prevalence of the overweight status in children grew from 5% to 11% from 1960s to 1990s. The epidemic of obesity has been paralleled by an increase in the incidence of chronic kidney disease (CKD) and hypertension. Results of several studies have demonstrated that obesity and metabolic syndrome were independent predictors of renal injury. The pathophysiology of obesity related hypertension is complex, including activation of sympathetic nervous system, renin angiotensin aldosterone system, hyperinsulinemia and inflammation. These same mechanisms likely contribute to the development of increased blood pressure in children. This review summarizes the recent epidemiologic data linking obesity with CKD and hypertension in children, as well as the potential mechanisms.

  9. Angiotensin II, Aldosterone, and Anti-Inflammatory Lymphocytes: Interplay and Therapeutic Opportunities

    Directory of Open Access Journals (Sweden)

    Daniel Arthur B. Kasal

    2012-01-01

    Full Text Available Inflammation is recognized as an important factor in the pathophysiology of hypertension, with the renin-angiotensin-aldosterone system (RAAS playing a key role in the disease. Initially described because of its contribution to extracellular fluid and electrolyte homeostasis, the RAAS has been implicated in endothelial dysfunction, vascular remodeling, oxidative stress, proinflammatory cytokine production, and adhesion molecule synthesis by the vascular wall. Both angiotensin II and aldosterone are involved in these systemic effects, activating innate and adaptive immune responses. This paper highlights some aspects connecting RAAS to the hypertensive phenotype, based on experimental and clinical studies, with emphasis on new findings regarding the contribution of an increasingly studied population of T lymphocytes: the T-regulatory lymphocytes. These cells can suppress inflammation and may exert beneficial vascular effects in animal models of hypertension.

  10. Circulatory abnormalities in cirrhosis with focus on neurohumoral aspects

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    1997-01-01

    Patients with cirrhosis exhibit characteristic hemodynamic changes with a hyperkinetic circulation and an abnormal distribution of the blood volume and neurohumoral regulation. Their plasma and noncentral blood volumes are increased, and the central and arterial blood volume and systemic vascular...... and hyperkinetic circulation in cirrhosis. Various vasodilators such as atrial natriurectic peptide, calcitonin gene-related peptide, adrenomedullin, and nitric oxide are among potential candidates in the arterial vasodilatation in cirrhosis. Besides enhanced sympathetic nervous activity, activation of the renin......-angiotensin-aldosterone system, and elevated circulating vasopressin, endothelin-1 may also be implicated in the hemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the hemodynamic and neurohumoral abnormalities in cirrhosis are part of a general circulatory dysfunction influencing...

  11. Salt reduction and hypertension in China: a concise state-of-the-art review

    Science.gov (United States)

    Liu, Yue; Li, Huiyan; Hong, Siting

    2015-01-01

    Hypertension (HTN) and its cardiovascular complications such as stroke and heart failure are a serious public health problem around the world. A growing number of studies confirm that salt plays an important role in the development of HTN. Increasing intake of salt leads to abnormal transport of sodium ions at the cellular level with activation of the sympathetic nervous system and renin-angiotensin-aldosterone system. Studies have shown that salt restriction can reduce blood pressure (BP) in patients with HTN, especially salt-sensitive HTN. Public health interventions to reduce salt intake, with the goal of decreasing adverse outcomes have been launched in numerous countries. In this review we will summarize the epidemiology of cardiovascular diseases and their risk factors, the relationship between salt and HTN, the effect of salt restriction on HTN and the current situation of prevention and treatment of HTN by salt reduction in China. PMID:26090330

  12. Hypertension and obesity: epidemiology, mechanisms and clinical approach.

    Science.gov (United States)

    Becton, Lauren J; Shatat, Ibrahim F; Flynn, Joseph T

    2012-08-01

    Obesity-related hypertension in pediatric patients is becoming more prevalent around the world as a consequence of the childhood obesity epidemic. Hypertension and the metabolic abnormalities associated with obesity will significantly increase the health risks for these children as they grow into adulthood. The pathophysiology of obesity-related hypertension is complex, and multiple potential mechanisms likely contribute to the development of higher blood pressure in obese children. These include hyperinsulinemia, activation of the renin-angiotensin-aldosterone system, stimulation of the sympathetic nervous system, abnormalities in adipokines such as leptin, direct effects of perinephric fat on the renal parenchyma, and cytokines acting at the vascular endothelial level. As in any child with elevated blood pressure, diagnostic evaluation should focus on confirmation of hypertension, determine if an underlying cause can be identified and whether hypertensive target organ damage is present. Therapy should begin with lifestyle modifications, but will often need to include one or more antihypertensive medications.

  13. [Obesity and hypertension].

    Science.gov (United States)

    Simonyi, Gábor; Kollár, Réka

    2013-11-01

    The frequency of hypertension and obesity is gradually growing in Hungary. At present 68.5% of men and 78% of women are obese. Hypertension and obesity are the most important risk factors of morbidity and mortality from cardiovascular disease. The relationship between increased sympathetic activity and hypertension is well known. Waist circumference and body fat mass correlate significantly with sympathetic activity, in which hyperlipidemia plays also a role. The increased activity of renin-angiotensin-aldosterone system via its vascular and renal effects also contributes to an increase of blood pressure. Increased sympathetic activity with decreasing vagal tone accompanying the imbalance of the autonomous nervous system is independent and significant risk factor of cardiovascular events including sudden cardiac death.

  14. Recent advances in treatment of heart failure [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Takeshi Kitai

    2015-12-01

    Full Text Available With the total cases and economic burden of heart failure continuing to rise, there is an overwhelming need for novel therapies. Several drugs for heart failure have succeeded in preclinical and early-phase clinical trials, but most of them failed to show the real benefit in pivotal clinical trials. Meanwhile, the US Food and Drug Administration recently approved two promising new drugs to treat heart failure: ivabradine and sacubitril/valsartan. Furthermore, some of the newer agents in testing offer the potential for significant progress in addition to these drugs. Patiromer and zirconium cyclosilicate are attractive agents that are expected to prevent hyperkalemia during renin-angiotensin-aldosterone system inhibition, and serelaxin and urodilatin are promising drugs in the treatment of acute heart failure. Future clinical trials with more appropriate study designs, optimal clinical endpoints, and proper patient selection are mandatory to assess the true efficacy of these attractive compounds in clinical practice.

  15. Hypercholesterolemia and Hypertension: Two Sides of the Same Coin.

    Science.gov (United States)

    Ivanovic, Branislava; Tadic, Marijana

    2015-12-01

    The aim of this review article is to summarize the current knowledge about mechanisms that connect blood pressure regulation and hypercholesterolemia, the mutual interaction between hypertension and hypercholesterolemia, and their influence on atherosclerosis development. Our research shows that at least one-third of the population of Western Europe has hypertension and hypercholesterolemia. Several biohumoral mechanisms could explain the relationship between hypertension and hypercholesterolemia and the association between these risk factors and accelerated atherosclerosis. The most investigated mechanisms are the renin-angiotensin-aldosterone system, oxidative stress, endothelial dysfunction, and increased production of endothelin-1. Arterial hypertension is frequently observed in combination with hypercholesterolemia, and this is related to accelerated atherosclerosis. Understanding the mechanisms behind this relationship could help explain the benefits of therapy that simultaneously reduce blood pressure and cholesterol levels.

  16. RAAS and stress markers in acute ischemic stroke

    DEFF Research Database (Denmark)

    Back, C.; Thiesen, K L; Olsen, Karsten Skovgaard;

    2015-01-01

    OBJECTIVES: Angiotensin II type 1 receptor blockade has neuroprotective effects in animal stroke models, but no effects in clinical stroke trials. We evaluated cerebral and peripheral changes in the renin angiotensin aldosterone system (RAAS) and stress responses in acute ischemic stroke patients....... MATERIALS AND METHODS: Blood from a jugular and cubital vein was collected within 48 h of stroke onset, after 24 and 48 h, and renin, angiotensin I, angiotensin II, aldosterone, norepinephrine, epinephrine, and cortisol were measured. Post-stroke cubital vein samples were collected after 8 (4.7-10) months......-stroke. No differences in RAAS were detected between jugular and cubital plasma levels. Jugular venous plasma levels of epinephrine and cortisol were elevated in the acute phase compared to cubital levels (P cortisol levels in the jugular vein blood may reflect a higher...

  17. Obesity and arterial compliance alterations.

    Science.gov (United States)

    Seifalian, Alexander M; Filippatos, Theodosios D; Joshi, Jatin; Mikhailidis, Dimitri P

    2010-03-01

    Obesity is associated with increased cardiovascular disease (CVD) risk, especially when excess body fat is distributed preferentially within the abdominal region. Obese subjects usually have increased arterial stiffness compared with non-obese subjects of similar age. The factors associated with increased arterial stiffness in obesity include endothelial dysfunction (decreased nitric oxide bioavailability), impaired smooth muscle cell function, insulin resistance, as well as elevated cholesterol and C-peptide levels. Furthermore, visceral fat, the adipose tissue-related renin-angiotensin-aldosterone system and hyperleptinaemia contribute to the obesity-associated impaired arterial compliance. Weight loss improves CVD risk factors and arterial compliance. Because increased arterial stiffness is a marker of CVD risk these findings support the concept that the presence of obesity has vascular implications.

  18. Hypertension in the African American population: A succinct look at its epidemiology, pathogenesis, and therapy.

    Science.gov (United States)

    Ortega, Luis M; Sedki, Emad; Nayer, Ali

    2015-01-01

    Arterial hypertension is prevalent in the black population in the United States. It is directly related to cardiovascular and kidney damage. Its pathogenesis is complex and includes the high incidence of obesity, salt sensitivity and the activation of the renin-angiotensin-aldosterone system. This complexity requires a therapeutic combination that includes changes in dietary habits and appropriate antihypertensive regimes. The International Society of Hypertension in Blacks recommends initiating dietary intervention for values of systolic/diastolic arterial blood pressure above 115/75 mmHg and maintaining arterial blood pressure below 135/85 mmHg using appropiate antihypertensive medication. The most adequate antihypertensive drug for this population has yet to be determined. Copyright © 2015. Published by Elsevier España, S.L.U.

  19. Pharmacological modulation of arterial stiffness.

    LENUS (Irish Health Repository)

    Boutouyrie, Pierre

    2011-09-10

    Arterial stiffness has emerged as an important marker of cardiovascular risk in various populations and reflects the cumulative effect of cardiovascular risk factors on large arteries, which in turn is modulated by genetic background. Arterial stiffness is determined by the composition of the arterial wall and the arrangement of these components, and can be studied in humans non-invasively. Age and distending pressure are two major factors influencing large artery stiffness. Change in arterial stiffness with drugs is an important endpoint in clinical trials, although evidence for arterial stiffness as a therapeutic target still needs to be confirmed. Drugs that independently affect arterial stiffness include antihypertensive drugs, mostly blockers of the renin-angiotensin-aldosterone system, hormone replacement therapy and some antidiabetic drugs such as glitazones. While the quest continues for \\'de-stiffening drugs\\

  20. A new look at electrolyte transport in the distal tubule.

    Science.gov (United States)

    Eladari, Dominique; Chambrey, Régine; Peti-Peterdi, Janos

    2012-01-01

    The distal nephron plays a critical role in the renal control of homeostasis. Until very recently most studies focused on the control of Na(+), K(+), and water balance by principal cells of the collecting duct and the regulation of solute and water by hormones from the renin-angiotensin-aldosterone system and by antidiuretic hormone. However, recent studies have revealed the unexpected importance of renal intercalated cells, a subtype of cells present in the connecting tubule and collecting ducts. Such cells were thought initially to be involved exclusively in acid-base regulation. However, it is clear now that intercalated cells absorb NaCl and K(+) and hence may participate in the regulation of blood pressure and potassium balance. The second paradigm-challenging concept we highlight is the emerging importance of local paracrine factors that play a critical role in the renal control of water and electrolyte balance.

  1. Calcium channel blocker prevents stress-induced activation of renin and aldosterone in conscious pig

    Energy Technology Data Exchange (ETDEWEB)

    Ceremuzynski, L.K.; Klos, J.; Barcikowski, B.; Herbaczynska-Cedro, K. (Department of Cardiology, Postgraduate Medical School, Warsaw (Poland))

    1991-06-01

    A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, the authors studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress. Renin and aldosterone levels were repeatedly measured by radioimmunoassay in blood samples taken periodically over 24 hours from a chronically implanted arterial cannula. Pretreatment of the animals (N = 11) with nisoldipine, 2 {times} 20 mg p.o. daily for 2 days before and on the day of immobilization, transiently attenuated the stress-induced increase of plasma renin activity and completely prevented the rise of aldosterone, as compared to nontreated controls (N = 10). The finding that nisoldipine suppresses RAA activation induced by a nonpharmacologic stimulus in the conscious intact animal may have clinical implications.

  2. Feline primary hyperaldosteronism: an emerging endocrine disease

    Directory of Open Access Journals (Sweden)

    Daniel Diola Bento

    2016-04-01

    Full Text Available ABSTRACT: The primary hyperaldosteronism, an endocrine disease increasingly identified in cats, is characterized by adrenal gland dysfunction that interferes with the renin-angiotensin-aldosterone system, triggering the hypersecretion of aldosterone. Pathophysiological consequences of excessive aldosterone secretion are related to increased sodium and water retention, and increased excretion of potassium, which induce hypertension and severe hypokalemia, respectively. The most common clinical findings in cats include: polydipsia, nocturia, polyuria, generalized weakness, neck ventroflexion, syncope, anorexia, weight loss, pendulous abdomen and blindness. Diagnosis is based on the evidence of hormonal hypersecretion with suppression of renin release, imaging and histopathological evaluation of adrenal glands. Treatment may be curative with adrenalectomy, in cases of unilateral disease, or conservative, through administration of aldosterone antagonists, potassium supplementation and antihypertensives. Prognosis varies from fair to good with the appropriate therapy. This article reviews the main aspects of primary aldosteronism in cats, providing the clinician with important information for the diagnosis of this disease.

  3. Aldosterone and vascular damage.

    Science.gov (United States)

    Duprez, D; De Buyzere, M; Rietzschel, E R; Clement, D L

    2000-06-01

    Although the aldosterone escape mechanism is well known, aldosterone has often been neglected in the pathophysiologic consequences of the activated renin-angiotensin-aldosterone system in arterial hypertension and chronic heart failure. There is now evidence for vascular synthesis of aldosterone aside from its secretion by the adrenal cortex. Moreover, aldosterone is involved in vascular smooth muscle cell hypertrophy and hyperplasia, as well as in vascular matrix impairment and endothelial dysfunction. The mechanisms of action of aldosterone may be either delayed (genomic) or rapid (nongenomic). Deleterious effects of aldosterone leading to vascular target-organ damage include (besides salt and water retention) decreased arterial and venous compliance, increased peripheral vascular resistance, and impaired autonomic vascular control due to baroreflex dysfunction.

  4. Infliximab in the treatment of amyloidosis secondary to Crohn's disease.

    Science.gov (United States)

    Cabezuelo, Juan B; Egea, Juan P; Ramos, Fernanda; Torrella, Emilio; Muray, Salomé; Alcázar, Concepción

    2012-05-14

    Secondary amyloidosis (AA) is a severe complication of progressed Crohn’s disease (CD) for which no effective treatment exists. We present the exceptional case of a 33 year-old male with moderate renal failure and proteinuria, who was simultaneously diagnosed with AA amyloid nephropathy and oligosymptomatic CD. He was treated with infliximab at 5mg/kg/8 weeks for 4 years, azathioprine at 1-1.5mg/kg/day (first year) and renin-angiotensin-aldosterone system blockers, with no complications. Treatment caused a decrease in proteinuria, improved renal function, and improved inflammatory parameters over time. Inspired by this case, we performed a review of the medical literature and found that infliximab could be a useful tool in the early treatment of amyloidosis secondary to CD.

  5. Vascular Stiffness in Insulin Resistance and Obesity

    Directory of Open Access Journals (Sweden)

    Guanghong eJia

    2015-08-01

    Full Text Available Obesity, insulin resistance, and type 2 diabetes are associated with a substantially increased prevalence of vascular fibrosis and stiffness, with attendant increased risk of cardiovascular and chronic kidney disease. Although the underlying mechanisms and mediators of vascular stiffness are not well understood, accumulating evidence supports the role of metabolic and immune dysregulation related to increased adiposity, activation of the renin angiotensin aldosterone system, reduced bioavailable nitric oxide, increased vascular extracellular matrix (ECM and ECM remodeling in the pathogenesis of vascular stiffness. This review will give a brief overview of the relationship between obesity, insulin resistance and increased vascular stiffness to provide a contemporary understanding of the proposed underlying mechanisms and potential therapeutic strategies.

  6. Direct renin inhibition in chronic kidney disease

    DEFF Research Database (Denmark)

    Persson, Frederik; Rossing, Peter; Parving, Hans-Henrik

    2013-01-01

    that renin inhibition could hold potential for improved treatment in patients with chronic kidney disease, with diabetic nephropathy as an obvious group of patients to investigate, as the activity of the renin-angiotensin-aldosterone system is enhanced in these patients and as there is an unmet need...... early as a beneficial effect was unlikely and there was an increased frequency of side effects. Also in non-diabetic kidney disease a few intervention studies have been carried out, but there is no ongoing hard outcome study. In this review we provide the current evidence for renin inhibition in chronic...... kidney disease by reporting of the studies published so far as well as perspective on the future possibilites....

  7. Review of and Updates on Hypertension in Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Masood Ahmad

    2017-01-01

    Full Text Available Obstructive sleep apnea (OSA is a prevalent sleep disorder as is hypertension (HTN in the 21st century with the rising incidence of obesity. Numerous studies have shown a strong association of OSA with cardiovascular morbidity and mortality. There is overwhelming evidence supporting the relationship between OSA and hypertension (HTN. The pathophysiology of HTN in OSA is complex and dependent on various factors such as sympathetic tone, renin-angiotensin-aldosterone system, endothelial dysfunction, and altered baroreceptor reflexes. The treatment of OSA is multifactorial ranging from CPAP to oral appliances to lifestyle modifications to antihypertensive drugs. OSA and HTN both need prompt diagnosis and treatment to help address the growing cardiovascular morbidity and mortality due to these two entities.

  8. From Water to Aquaretics: a Legendary Route

    Directory of Open Access Journals (Sweden)

    Valentina Donato

    2014-05-01

    Full Text Available Man is water. When life appeared on earth, the primordial cell had a simple structure and could immediately ascertain from the surrounding aquatic environment the substances for nutrition and oxygen, without any need for structural complexity. As part of evolution, during the transition from aquatic to terrestrial life, vertebrates had to fight against dehydration as well as fish in the sea. In this complex mechanism of osmoregulation, the structure and function of some osmoregulatory hormones have been maintained during the evolution of species, from fish to man. Within the homeostatic mechanism, the renin-angiotensin-aldosterone system (RAAS is crucial in the regulation of renal reasorption of water and sodium. It is also involved in the regulation of renal plasma flux, blood volume and blood pressure. Vasopressin plays a hormonal function in the mechanisms of water homeostasis acting through Aquaporins (AQP, channel-proteins that allow bi-directional water transport across cell membranes.

  9. EFFECTS OF ANGIOTENSIN II BLOCKADE WITH IRBESARTAN ON INFLAMMATORY MARKERS IN HAEMODIALYSIS PATIENTS: A RANDOMISED DOUBLE BLIND PLACEBO CONTROLLED ONE-YEAR FOLLOW-UP TRIAL (SAFIR STUDY)

    DEFF Research Database (Denmark)

    Peters, Christian Daugaard; Kjærgaard, Krista Dybtved; Nielsen, Claus H.

    activities in inflammation, and previous studies suggest an anti-inflammatory effect of angiotensin II receptor blocker (ARB) treatment. The aim of this study was to compare the effect of ARB versus placebo on plasma concentrations of inflammatory markers in HD patients. Methods Adult HD patients were...... No significant short-term or long-term anti-inflammatory effect of irbesartan treatment was observed. Our findings suggest that in HD patients antihypertensive treatment with irbesartan (and most likely ARBs in general) does not have clinically relevant BP-independent effects that favourably impact......Introduction Haemodialysis (HD) patients are exposed to various endogenous and exogenous factors, which in their sum contribute to a chronic inflammatory state evidenced by increased levels of pro-inflammatory cytokines. The renin-angiotensin-aldosterone system (RAAS) has important modulating...

  10. 不同全麻诱导药对高血压病人围诱导期血浆R-A-A-S系统的影响

    Institute of Scientific and Technical Information of China (English)

    赵国庆; 王显春

    2002-01-01

    @@ 在全身动脉血压的调节中,肾素-血管紧张素-醛固酮系统(Renin-angiotensin-aldosterone system,R-A-A-S)具有非常关键性的作用,围手术期对血浆肾素活性(Plasmarenin activity,PRA)、血管紧张素Ⅱ(angiotensinⅡ,AⅡ)和醛固酮(aldosterone,Ald)系统的研究较多[1,2],本研究旨在观察不同全麻诱导药对原发性高血压病人围诱导期血浆R-A-A-S的影响,评估原发性高血压病人在全麻诱导时药物的最佳选择.

  11. Progress in aldosterone-induced myocardial fibrosis and mechanism underlying its signal transduction%醛固酮致心肌纤维化及其信号转导机制研究进展

    Institute of Scientific and Technical Information of China (English)

    谢永进

    2011-01-01

    心肌纤维化(myocardial fibrosis,MF)是高血压、心肌梗死、心力衰竭等多种心脏疾病终末阶段的共同病理改变,肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system,RAAS)是MF发生发展的重要神经内分泌机制.醛固酮(aldosterone,ALD)导致MF信号转导的分子机制近年来取得了一些进展,信号网络相当复杂,有待进一步明确和深入研究.

  12. Hemodynamic effects of barnidipine hydrochloride in conscious squirrel monkeys.

    Science.gov (United States)

    Shibasaki, M; Inagaki, O; Takenaka, T

    1994-05-01

    1. The effects of barnidipine, a new dihydropyridine Ca2+ antagonist, on cardiovascular and renin-angiotensin-aldosterone systems were investigated in conscious squirrel monkeys. 2. Barnidipine (0.3-3 mg/kg p.o.) produced a dose-related decrease in systolic blood pressure. The hypotensive action after 3 mg/kg p.o. lasted more than 8 hr. 3. Barnidipine increased heart rate, but did not affect the PQ-interval of the electrocardiograph. 4. Barnidipine (1 and 3 mg/kg p.o.) increased plasma renin activity dose-dependently. However, it had no significant effect on plasma aldosterone concentration. 5. These results indicate that barnidipine produces a sustained hypotension without affecting atrioventricular conduction time and plasma aldosterone concentration in conscious squirrel monkeys.

  13. ANGIOTENSIN RECEPTOR BLOCKERS WITH PLEIOTROPIC PROPERTIES: A NEW STANDARD IN CARDIOVASCULAR RISK MANAGEMENT AND TREATMENT OF HYPERTENSION

    Directory of Open Access Journals (Sweden)

    V. I. Podzolkov

    2017-01-01

    Full Text Available An increase in the activity of the renin-angiotensin-aldosterone system is one of the most important mechanisms for the realization of the cardiovascular continuum. The role that angiotensin receptor blockers play in achieving target figures of blood pressure and reducing cardiovascular risk is discussed. The importance of pleiotropic properties of angiotensin receptor blockers (in particular, activation of peroxisome proliferator-activated receptors gamma – PPAR-γ in the management of patients with insulin resistance, obesity, dyslipidemia is also covered. The evidence base for the use of telmisartan as a drug with pleiotropic effect in patients with arterial hypertension and associated diseases (diabetes mellitus, obesity, renal dysfunction is discussed. 

  14. The Role of Uric Acid in Hypertension of Adolescents, Prehypertension and Salt Sensitivity of Blood Pressure

    Science.gov (United States)

    Wang, Yang; Hu, Jia-Wen; Lv, Yong-Bo; Chu, Chao; Wang, Ke-Ke; Zheng, Wen-Ling; Cao, Yu-Meng; Yuan, Zu-Yi; Mu, Jian-Jun

    2017-01-01

    Uric acid is the end product of purine metabolism. Metabolic disorders of uric acid are associated with many disease states. Substantial evidence suggests the possible role of uric acid as a mediator of high blood pressure. Elevated uric acid is closely associated with new onset essential hypertension in adolescents and prehypertension; and urate-lowering agents can significantly improve these early stages of hypertension. Uric acid also influences salt sensitivity of blood pressure through two phases. Local renin-angiotensin-aldosterone system activation initiates renal damage, arteriolopathy, and endothelium dysfunction, which is followed by the dysregulation of sodium homeostasis, thereby leading to increased salt sensitivity. In this review we summarize the available evidence to contribute to a better understanding of the casual relationship between uric acid and early or intermediate stages of hypertension. We hope our review can contribute to the prevention of hypertension or provide new insights into a treatment that would slow the progression of hypertension. PMID:28190873

  15. Proteinuric diseases with sodium retention: Is plasmin the link?

    DEFF Research Database (Denmark)

    Svenningsen, Per; Skøtt, Ole; Jensen, Boye L

    2012-01-01

    1. Sodium retention in disease states characterized by proteinuria, such as nephrotic syndrome, preeclampsia, and diabetic nephropathy, occurs through poorly understood mechanism(s). 2. In the nephrotic syndrome, data from experimental and clinical studies indicate that the sodium retention...... originates in the renal cortical collecting duct and involves hyper-activity of the epithelial sodium channel (ENaC). 3. The stimulus for the increased ENaC activity does not appear to involve any of the classical sodium retaining mechanisms, such as the renin-angiotensin-aldosterone system, arginine...... aminonucleoside (PAN) rat model of nephrotic syndrome. 6. This finding suggests that a defective glomerular filtration barrier allows filtration into the tubular fluid of substances that activate ENaC and enhance sodium reabsorption. This concept may be expanded to other disease state, such as preeclampsia...

  16. Cardiac Hypertrophy and Fibrosis in the Metabolic Syndrome: A Role for Aldosterone and the Mineralocorticoid Receptor

    Directory of Open Access Journals (Sweden)

    Eric E. Essick

    2011-01-01

    Full Text Available Obesity and hypertension, major risk factors for the metabolic syndrome, render individuals susceptible to an increased risk of cardiovascular complications, such as adverse cardiac remodeling and heart failure. There has been much investigation into the role that an increase in the renin-angiotensin-aldosterone system (RAAS plays in the pathogenesis of metabolic syndrome and in particular, how aldosterone mediates left ventricular hypertrophy and increased cardiac fibrosis via its interaction with the mineralocorticoid receptor (MR. Here, we review the pertinent findings that link obesity with elevated aldosterone and the development of cardiac hypertrophy and fibrosis associated with the metabolic syndrome. These studies illustrate a complex cross-talk between adipose tissue, the heart, and the adrenal cortex. Furthermore, we discuss findings from our laboratory that suggest that cardiac hypertrophy and fibrosis in the metabolic syndrome may involve cross-talk between aldosterone and adipokines (such as adiponectin.

  17. Common drugs for stabilization of renal function in the progression of diabetic nephropathy and their relations with hypertension therapy.

    Science.gov (United States)

    Wang, Yuxuan; Wang, Chengcheng; Zhang, Xiuli; Gu, Harvest F; Wu, Liang

    2017-02-14

    Diabetic nephropathy is characterized by hypertension, progressive albuminuria, glomerulosclerosis and declines in glomerular filtration rate leading to end stage renal disease. Although the pathogenesis of diabetic nephropathy is not fully understood, current treatment of the patients with diabetic nephropathy is mainly based upon the control of hyperglycaemia and management of blood pressures. Several drugs, which are originally developed for hypertension therapy, have been adopted for stabilization of renal function in diabetic nephropathy. In this review, we first discuss the relationships between diabetic nephropathy and hypertension particularly in the renin-angiotensin-aldosterone system. We then summarize chemical structures, pharmacological characteristics and clinical studies of the common drugs used for treatment of diabetic nephropathy, while these drugs have effects against hypertension. This review may provide the constructive information for further drug development in diabetic nephropathy.

  18. Renal sympathetic denervation prevents the development of pulmonary arterial hypertension and cardiac dysfunction in dogs.

    Science.gov (United States)

    Hu, Wei; Yu, Sheng-Bo; Chen, Liao; Guo, Rui-Qiang; Zhao, Qing-Yan

    2015-08-01

    The renin-angiotensin-aldosterone system is activated in pulmonary arterial hypertension (PAH) patients, and this activation may have long-term negative effects on the progression of PAH. The purpose of this study was to evaluate the effects of transcatheter renal sympathetic denervation (RSD) on the development of pulmonary arterial hypertension and cardiac dysfunction in dogs using two-dimensional speckle tracking imaging. Twenty-two dogs were randomly divided into three groups: control group (n = 7), PAH group (n = 8), and PAH + RSD group (n = 7). All dogs were assessed using two-dimensional speckle tracking imaging. The ventricular strain, ventricular synchrony, left ventricular (LV) twist, and torsion rate were analyzed to evaluate cardiac function. After 8 weeks, the right ventricular lateral longitudinal strain and the septum longitudinal strain were reduced in the PAH group compared with the control group (p dogs.

  19. Effect of 4 years subcutaneous insulin infusion treatment on albuminuria, kidney function and HbA1c compared with multiple daily injections

    DEFF Research Database (Denmark)

    Vestergaard Rosenlund, Signe; Hansen, T W; Andersen, Steen

    2015-01-01

    , diabetes duration, estimated GFR, UACR, mean arterial pressure, HbA1c , cholesterol, renin-angiotensin-aldosterone system inhibition, anti-hypertensive treatment and smoking (P ...AIM: The effect of insulin pump [continuous subcutaneous insulin infusion (CSII)] treatment on diabetes complications in a modern clinical setting is largely unknown. We investigated the effect of 4 years CSII treatment on HbA1c, albuminuria and kidney function compared with multiple daily...... on diabetes duration, gender, HbA1c and normo-, micro- or macroalbuminuria at baseline. Urinary albumin/creatinine ratio (UACR) was measured yearly and annual change assessed from linear regression. RESULTS: CSII- vs. MDI-treated patients were comparable at baseline. After 4 years, HbA1c was 62 ± 11 vs. 68...

  20. Adipokines and cardiovascular disease: A comprehensive review.

    Science.gov (United States)

    Smekal, Ales; Vaclavik, Jan

    2017-03-01

    Adipokines are peptides that signal the functional status of adipose tissue to the brain and other target organs. In adipose tissue dysfunction, adipokine secretion is altered, and this can contribute to a spectrum of obesity-associated conditions including cardiovascular disease. Some adipokines have anti-inflammatory and cardioprotective effects (omentin, apelin, adiponectin). Others are pro-inflammatory with negative impact on cardiovascular function (leptin, visfatin, resistin, adipocyte fatty-acid-binding protein). In the first part, this article reviews the endocrine functions of adipose tissue in general, effects of the distribution and composition of fat tissue, and the roles of cortisol and the renin-angiotensin-aldosterone system in the development of the inflammatory state of addipose tissue. In the second part, the known cardiovascular effects of different adipokines and their clinical potential are discussed in detail.

  1. Controversial issues in CKD clinical practice: position statement of the CKD-treatment working group of the Italian Society of Nephrology.

    Science.gov (United States)

    Bellizzi, Vincenzo; Conte, Giuseppe; Borrelli, Silvio; Cupisti, Adamasco; De Nicola, Luca; Di Iorio, Biagio R; Cabiddu, Gianfranca; Mandreoli, Marcora; Paoletti, Ernesto; Piccoli, Giorgina B; Quintaliani, Giuseppe; Ravera, Maura; Santoro, Domenico; Torraca, Serena; Minutolo, Roberto

    2017-04-01

    This position paper of the study group "Conservative treatment of Chronic Kidney Disease-CKD" of the Italian Society of Nephrology addresses major practical, unresolved, issues related to the conservative treatment of chronic renal disease. Specifically, controversial topics from everyday clinical nephrology practice which cannot find a clear, definitive answer in the current literature or in nephrology guidelines are discussed. The paper reports the point of view of the study group. Concise and practical advice is given on several common issues: renal biopsy in diabetes; dual blockade of the renin-angiotensin-aldosterone system (RAAS); management of iron deficiency; low protein diet; dietary salt intake; bicarbonate supplementation; treatment of obesity; the choice of conservative therapy vs. dialysis. For each topic synthetic statements, guideline-style, are reported.

  2. Peritoneal Dialysis in Diabetics: There Is Room for More

    Directory of Open Access Journals (Sweden)

    P. Cotovio

    2011-01-01

    Full Text Available End stage renal disease diabetic patients suffer from worse clinical outcomes under dialysis-independently of modality. Peritoneal dialysis offers them the advantages of home therapy while sparing their frail vascular capital and preserving residual renal function. Other benefits and potential risks deserve discussion. Predialysis intervention with early nephrology referral, patient education, and multidisciplinary support are recommended. Skilled and updated peritoneal dialysis protocols must be prescribed to assure better survival. Optimized volume control, glucose-sparing peritoneal dialysis regimens, and elective use of icodextrin are key therapy strategies. Nutritional evaluation and support, preferential use of low-glucose degradation products solutions, and prescription of renin-angiotensin-aldosterone system acting drugs should also be part of the panel to improve diabetic care under peritoneal dialysis.

  3. Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers

    DEFF Research Database (Denmark)

    Lambers Heerspink, Hiddo J; Holtkamp, Frank A; Parving, Hans-Henrik

    2012-01-01

    Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis...... of the RENAAL and IDNT trials to test this in patients with type 2 diabetic nephropathy randomized to ARB or non-renin-angiotensin-aldosterone system (non-RAASi)-based antihypertensive therapy. Treatment effects on renal and cardiovascular outcomes were compared in subgroups based on dietary sodium intake...... effects of ARB compared with non-RAASi-based therapy on renal and cardiovascular outcomes were greater in patients with type 2 diabetic nephropathy with lower than higher dietary sodium intake. This underscores the avoidance of excessive sodium intake, particularly in type 2 diabetic patients receiving...

  4. Hypercortisolism in obesity-associated hypertension.

    Science.gov (United States)

    Varughese, Amy G; Nimkevych, Oksana; Uwaifo, Gabriel I

    2014-07-01

    Obesity is prevalent worldwide and associated with co-morbidities that result in increased cardiovascular risk. Hypertension is the most prevalent obesity comorbidity associated with increased cardiovascular risk. Obesity hypertension is a distinct subtype of essential hypertension. While endogenous Cushing's syndrome is an uncommon cause of both obesity and hypertension, the recent recognition of other hypercortisolemic states has raised the profile of hypercortisolism as an important contributor in obesity hypertension. The high prevalence of exogenous, iatrogenic, pseudo, and subclinical Cushing's syndromes makes hypercortisolism an important diagnostic consideration in the evaluation and management of patients with obesity hypertension who are resistant to conventional management. Available data suggest that the renin-angiotensin-aldosterone system modulating antihypertensives have the best efficacy in hypercortisolism-mediated obesity hypertension. Strategies aimed at reducing cortisol production and action also have utility. This review provides a comprehensive overview of the epidemiology, etiopathogenesis and management options available for glucocorticoid-mediated obesity hypertension.

  5. Obesity, hypertension, and chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Hall ME

    2014-02-01

    Full Text Available Michael E Hall,1,2 Jussara M do Carmo,2 Alexandre A da Silva,2 Luis A Juncos,1,2 Zhen Wang,2 John E Hall2 1Department of Medicine, 2Department of Physiology and Biophysics, Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, USA Abstract: Obesity is a major risk factor for essential hypertension, diabetes, and other comorbid conditions that contribute to development of chronic kidney disease. Obesity raises blood pressure by increasing renal tubular sodium reabsorption, impairing pressure natriuresis, and causing volume expansion via activation of the sympathetic nervous system and renin-angiotensin-aldosterone system and by physical compression of the kidneys, especially when there is increased visceral adiposity. Other factors such as inflammation, oxidative stress, and lipotoxicity may also contribute to obesity-mediated hypertension and renal dysfunction. Initially, obesity causes renal vasodilation and glomerular hyperfiltration, which act as compensatory mechanisms to maintain sodium balance despite increased tubular reabsorption. However, these compensations, along with increased arterial pressure and metabolic abnormalities, may ultimately lead to glomerular injury and initiate a slowly developing vicious cycle that exacerbates hypertension and worsens renal injury. Body weight reduction, via caloric restriction and increased physical activity, is an important first step for management of obesity, hypertension, and chronic kidney disease. However, this strategy may not be effective in producing long-term weight loss or in preventing cardiorenal and metabolic consequences in many obese patients. The majority of obese patients require medical therapy for obesity-associated hypertension, metabolic disorders, and renal disease, and morbidly obese patients may require surgical interventions to produce sustained weight loss. Keywords: visceral adiposity, type II diabetes, sodium reabsorption

  6. Effect of Mixed Corrosion Inhibitors in Cooling Water System

    Directory of Open Access Journals (Sweden)

    Dina Raheem

    2011-01-01

    Full Text Available The effect of mixed corrosion inhibitors in cooling system was evaluated by using carbon steel specimens and weight loss analysis. The carbon steel specimens immersed in mixture of sodium phosphate (Na2 HPO4 used as corrosion inhibitor and sodium glocunate (C6 H11 NaO7 as a scale dispersant at different concentrations (20,40, 60, 80 ppm and at different temperature (25,50,75 and 100ºC for (1-5 days. The corrosion inhibitors efficiency was calculated by using uninhibited and inhibited water to give 98.1%. The result of these investigations indicate that the corrosion rate decreases with the increase the corrosion inhibitors concentration at 80 ppm and at 100ºC for 5 days, (i.e, corrosion rate= 0.014gmd.

  7. Mechanisms regulating the renal excretion of sodium during pregnancy.

    Science.gov (United States)

    Robb, C A; Davis, J O; Johnson, J A; Blaine, E H; Schneider, E G; Baumber, J S

    1970-05-01

    Observations were made on the relation of the renin-angiotensin-aldosterone system and renal hemodynamic function to sodium balance in 43 pregnant dogs. Daily balance studies revealed that about 30-40% of ingested sodium was retained during the last half of pregnancy; during the same period, potassium balance was also positive but to a lesser extent. For groups of pregnant dogs, plasma renin activity (n = 14) and aldosterone secretion (n = 19) were significantly higher than normal; however, in some animals one or both functions were normal even though sodium retention was present. In contrast, plasma renin substrate concentration was consistently elevated during pregnancy in seven dogs. In a group of nine dogs in which both aldosterone secretion and plasma renin activity were measured, aldosterone secretion was elevated in the three dogs with the highest values for plasma renin activity; in two of the remaining six animals aldosterone secretion was elevated but plasma renin activity was normal or only slightly increased. The sequestration of sodium and water into the uterine contents was defined quantitatively in this study but evidence was lacking to support the idea that such changes led to renin release. The glomerular filtration rate (GFR) was significantly elevated throughout pregnancy but a significant decrease from the high level of mid-pregnancy occurred during the last half of pregnancy; this decrease in GFR probably contributed to the sodium retention. Administration of a large dose of deoxycorticosterone acetate (DOCA) to dogs in late pregnancy produced marked sodium retention but "escape" from the sodium-retaining steroid occurred. The data demonstrate that although increased activity of the renin-angiotensin-aldosterone system was frequently present during pregnancy, a normal rate of aldosterone secretion occurred. This finding and the observed "escape" from DOCA suggest the existence of sodium-retaining mechanisms other than the mechanism provided by

  8. Anti-hypertensive drug treatment of patients with and the metabolic syndrome and obesity: a review of evidence, meta-analysis, post hoc and guidelines publications.

    Science.gov (United States)

    Owen, Jonathan G; Reisin, Efrain

    2015-06-01

    Epidemiological studies have shown an increasing prevalence of obesity and the metabolic syndrome worldwide. Lifestyle modifications that include dietary changes, weight reduction, and exercise are the cornerstones in the treatment of this pathology. However, adherence to this approach often meets with failure in clinical practice; therefore, drug therapy should not be delayed. The ideal pharmacological antihypertensive regimen should target the underlying mechanisms involved in this syndrome, including sympathetic activation, increased renal tubular sodium reabsorption, and overexpression of the renin-angiotensin-aldosterone system by the adipocyte. Few prospective trials have been conducted in the search of the ideal antihypertensive regimen in patients with obesity and the metabolic syndrome. We summarize previously published ad hoc studies, prospective studies, and guideline publications regarding the treatment of hypertension in patients with obesity and the metabolic syndrome. We conclude that the optimal antihypertensive drug therapy in these patients has not been defined. Though caution exists regarding the use of thiazide diuretics due to potential metabolic derangements, there is insufficient data to show worsened cardiovascular or renal outcomes in patients treated with these drugs. In regard to beta blockers, the risk of accelerating conversion to diabetes and worsening of inflammatory mediators described in patients treated with traditional beta blockers appears much less pronounced or absent when using the vasodilating beta blockers. Renin-angiotensin-aldosterone system (RAAS) inhibition with an ACE or an ARB and treatment with calcium channel blockers appears safe and well tolerated in obesity-related hypertension and in patients with metabolic syndrome. Future prospective pharmacological studies in this population are needed.

  9. Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis.

    Science.gov (United States)

    Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting; Larsson, Erik; Wåhlin, Nils; Jensen, Boye L; G Persson, A Erik; Carlström, Mattias

    2016-01-01

    Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates hypertension and restores the renal excretion pattern, which is associated with reduced renal NOX and components of the renin-angiotensin-aldosterone system. This study emphasizes a link between renal nerves, the development of hypertension, and modulation of NOX function.

  10. JS ISH-ISN-3 OPTIMAL TARGETS FOR BP CONTROL IN CKD.

    Science.gov (United States)

    Wheeler, David

    2016-09-01

    Hypertension is the most prevalent complication of chronic kidney disease (CKD). Lowering high blood pressure slows progressive loss of kidney function and may also reduce the associated risk of cardiovascular complications, a common cause of premature death in CKD patients.Current International Guidelines produced by Kidney Disease: Improving Global Outcomes (KDIGO) acknowledges that no single BP target is optimal for all CKD patients, and encourages individualization of treatment depending on age, the severity of albuminuria and comorbidities. When published in 2012, the available evidence indicated that in CKD patients without albuminuria, the target BP should be ≤140 mmHg systolic and ≤90 mmHg diastolic. However, in most patients with an albumin excretion rate of ≥30 mg/24 h (i.e., those with both micro- and macroalbuminuria), a lower target of ≤130 mmHg systolic and ≤80 mmHg diastolic was suggested. In achieving BP control, the value of lifestyle changes and the need for multiple pharmacological agents was acknowledged. Use of agents that block the renin-angiotensin-aldosterone system was recommended or suggested in all patients with an albumin excretion rate of ≥30 mg/24 h. Recommendations are almost identical in CKD patients with and without diabetes.Recent data from SPRINT (which included CKD patients) and other clinical trials has led nephrologists to ask whether targets lower than those recommend by KDIGO are appropriate and the guidelines are currently undergoing an update. Controversies remain around discontinuation of ACE/ARB in patients with stage 4-5 CKD and dual renin-angiotensin-aldosterone system blockade.

  11. and vein factor patIents Comparison between umbilical artery ...

    African Journals Online (AJOL)

    under the influence of the hypothalamus, have been postulated as being the source of ... According to clinical data collected during labour and from their antenatal .... Jesides the renin-angiotensin aldosterone, antidiuretic hormone. 1lIld atrial ...

  12. THE CAPABILITIES OF A REGISTER AS A QUALITY CONTROL OF THE PHARMACOTHERAPY IN OUTPATIENTS AT HIGH RISK OF CARDIOVASCULAR COMPLICATIONS (THE "LIS-1" REGISTER

    Directory of Open Access Journals (Sweden)

    M. L. Ginzburg

    2015-09-01

    Full Text Available Aim. To evaluate the frequency of the prescription of cardiovascular drugs in patients before the reference acute myocardial infarction (AMI based on the register "LIS-1" (Lubertsy mortality study of patients after myocardial infarction.Material and methods. Stage 1: development of the Register of patients with AMI admitted to cardiology departments of hospitals in Luberets district, Moscow region (2005-2007 and discharged for outpatient treatment. Median follow-up – 1.6 years (1.0, 2.4. The primary endpoint – total mortality. Stage 2: the continuation of register "LIS-1" (2011-2012.Results.1133 patients (mean age of men 60.1±0.5, women – 71.4±0.4 years were included in the 1st stage of the study; 172 (15.2% died in the hospital. Before the reference hospitalization 21.4% of patients had been receiving b-blockers, 35.3% - renin-angiotensin-aldosterone system (RAAS inhibitors, 15.7% - antiplatelet agents, 1.9% - statins, 13% of patients - diuretics. Statistically significant (adjusted for sex and age positive impact on hospital mortality reduction had a treatment with b-blockers [OR=0.542, CI=0.357-0.824, p=0.004] and RAAS inhibitors [OR=0.710; CI=0.512-0.986, p=0.040] prior to the development of acute myocardial infarction. As the number of patients receiving statins and antiplatelet agents was small, the contribution these drugs intake on hospital mortality was not identified. 272 patients (mean age 63.6±12.6 years were included on the second phase of the study. The information about the received therapy before reference hospitalization was reported by 173 patients: 39% of patients used b-blockers, 47% - RAAS inhibitors, 37% - antiplatelet agents, 15% - statins, 15% of patients - diuretics. Positive changes in the frequency of the prescription of essential drugs were observed in 5 years: a significant increase in number of patients with b-blockers (p<0.001, RAAS inhibitors (p<0.01, antiplatelet agents (p<0.05 and statins (p<0.001. The

  13. THE CAPABILITIES OF A REGISTER AS A QUALITY CONTROL OF THE PHARMACOTHERAPY IN OUTPATIENTS AT HIGH RISK OF CARDIOVASCULAR COMPLICATIONS (THE "LIS-1" REGISTER

    Directory of Open Access Journals (Sweden)

    M. L. Ginzburg

    2014-01-01

    Full Text Available Aim. To evaluate the frequency of the prescription of cardiovascular drugs in patients before the reference acute myocardial infarction (AMI based on the register "LIS-1" (Lubertsy mortality study of patients after myocardial infarction.Material and methods. Stage 1: development of the Register of patients with AMI admitted to cardiology departments of hospitals in Luberets district, Moscow region (2005-2007 and discharged for outpatient treatment. Median follow-up – 1.6 years (1.0, 2.4. The primary endpoint – total mortality. Stage 2: the continuation of register "LIS-1" (2011-2012.Results.1133 patients (mean age of men 60.1±0.5, women – 71.4±0.4 years were included in the 1st stage of the study; 172 (15.2% died in the hospital. Before the reference hospitalization 21.4% of patients had been receiving b-blockers, 35.3% - renin-angiotensin-aldosterone system (RAAS inhibitors, 15.7% - antiplatelet agents, 1.9% - statins, 13% of patients - diuretics. Statistically significant (adjusted for sex and age positive impact on hospital mortality reduction had a treatment with b-blockers [OR=0.542, CI=0.357-0.824, p=0.004] and RAAS inhibitors [OR=0.710; CI=0.512-0.986, p=0.040] prior to the development of acute myocardial infarction. As the number of patients receiving statins and antiplatelet agents was small, the contribution these drugs intake on hospital mortality was not identified. 272 patients (mean age 63.6±12.6 years were included on the second phase of the study. The information about the received therapy before reference hospitalization was reported by 173 patients: 39% of patients used b-blockers, 47% - RAAS inhibitors, 37% - antiplatelet agents, 15% - statins, 15% of patients - diuretics. Positive changes in the frequency of the prescription of essential drugs were observed in 5 years: a significant increase in number of patients with b-blockers (p<0.001, RAAS inhibitors (p<0.01, antiplatelet agents (p<0.05 and statins (p<0.001. The

  14. 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

  15. Small-Molecule Inhibitors of the Type III Secretion System

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    Lingling Gu

    2015-09-01

    Full Text Available Drug-resistant pathogens have presented increasing challenges to the discovery and development of new antibacterial agents. The type III secretion system (T3SS, existing in bacterial chromosomes or plasmids, is one of the most complicated protein secretion systems. T3SSs of animal and plant pathogens possess many highly conserved main structural components comprised of about 20 proteins. Many Gram-negative bacteria carry T3SS as a major virulence determinant, and using the T3SS, the bacteria secrete and inject effector proteins into target host cells, triggering disease symptoms. Therefore, T3SS has emerged as an attractive target for antimicrobial therapeutics. In recent years, many T3SS-targeting small-molecule inhibitors have been discovered; these inhibitors prevent the bacteria from injecting effector proteins and from causing pathophysiology in host cells. Targeting the virulence of Gram-negative pathogens, rather than their survival, is an innovative and promising approach that may greatly reduce selection pressures on pathogens to develop drug-resistant mutations. This article summarizes recent progress in the search for promising small-molecule T3SS inhibitors that target the secretion and translocation of bacterial effector proteins.

  16. Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR).

    Science.gov (United States)

    Weir, Matthew R; Kline, Irina; Xie, John; Edwards, Robert; Usiskin, Keith

    2014-09-01

    Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on serum electrolytes were evaluated using pooled data from studies of patients with type 2 diabetes mellitus (T2DM). Analyses were performed using two datasets, each including four placebo-controlled studies: Population 1 (N = 2215), patients with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) (mean = 89.6 mL/min/1.73 m(2)) and Population 2 (N = 721), patients with baseline eGFR ≥45 and canagliflozin 100 and 300 mg or placebo. Potassium changes were further evaluated based on baseline therapy with anti-hypertensive agents that interfere with potassium excretion (renin-angiotensin aldosterone system-acting agents and/or potassium-sparing diuretics). Mean percent changes from baseline in potassium with canagliflozin 100 and 300 mg and placebo were 0.6%, 1.0%, and 0.5%, respectively (Week 26; Population 1); and 1.7%, 2.8%, and 0.7%, respectively (Week 18/26; Population 2). The proportion of patients who had potassium elevations meeting pre-defined outlier criteria (>5.4 mmol/L [5.4 mEq/L] and >15% increase from baseline) with canagliflozin 100 and 300 mg and placebo was 4.5%, 6.8%, and 4.7% (Population 1); and 5.2%, 9.1%, and 5.5% (Population 2). In both populations, potassium elevations were usually canagliflozin or placebo; elevations ≥6.5 mmol/L were rare but more frequent in patients taking anti-hypertensive agents that affect potassium excretion in both the canagliflozin and placebo groups. Small mean percent changes in sodium, bicarbonate, and calcium were seen across groups in both populations; small mean percent increases in magnesium and phosphate were seen with canagliflozin vs placebo, but without an increase in patients meeting outlier criteria. Adverse events related to changes in electrolytes were low across groups. In patients with T2DM, canagliflozin was generally associated with small mean percent changes in serum

  17. CHOICE OF THE INITIAL TREATMENT FOR MILD TO MODERATE ARTERIAL HYPERTENSION IN MOSCOW PRIMARY PRACTICE

    Directory of Open Access Journals (Sweden)

    S. V. Gatsura

    2014-01-01

    Full Text Available Aim. To assess the choice of initial pharmacotherapy of uncomplicated mild to moderate arterial hypertension (HT in Moscow primary care as well as to clear up the influence of regulatory measures on this choice.Material and methods. Results of two similar surveys conducted in 2011-2012 (452 respondents and 2013-2014 (273 respondents were compared to estimate preferences of Moscow primary care physicians regarding initial antihypertensive agents for therapy of uncomplicated mild to moderate HT taking into consideration an influence of regulatory requirement to prescribe medicinal products by international nonproprietary name (INN since July 2012. All participants were proposed to write down their preferred antihypertensive agents for initial mono- or combined therapy of mild to moderate HT with moderate cardiovascular risk and absence of compelling indications.Results. Angiotensin converting enzyme inhibitors (ACEI remained the leading class of antihypertensive agents, though their popularity slightly but significantly declined from 44.4% in 2011-12 to 37.2% in 2013-14 (р<0.05. Angiotensin receptor blockers partially displaced the leaders and increased their popularity from 11.3% in 2011-12 to 18.0% in 2013-14 (р<0.01. ACEI/diuretic combination remained on the 3rd position (16.4% and 15.3% respectively. Beta-blockers and diuretics as monotherapy shared 4th and 5th places in this rating. Calcium channel blockers popularity among Moscow prescribers remained unchanged and poor – 2.1%. The most popular medicine by trade name was Noliprel, perindopril/indapamide fixed combination, – 14.0% and 13.7% of respondents in 2011-12 and 2013-14, respectively. The share of medicine products recommended by INN went up from 11.9% to 22.8% among top-10 popular medications (р<0.01.Conclusion. Blockers of renin-angiotensin-aldosterone system remain the leading drugs for the initial treatment of uncomplicated mild to moderate HT without compelling indications

  18. EVALUATION OF TREATMENT OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION BEFORE REFERENCE EVENT AND BEFORE DISCHARGE FROM THE HOSPITAL: REGISTER DATA (KHABAROVSK CITY. PART 2

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    L. N. Malay

    2017-01-01

    Full Text Available Aim. To study a treatment of patients with acute  myocardial infarction (AMI before  and during hospitalization in a Khabarovsk  hospital, which has an opportunity of primary percutaneous coronary  intervention (PCI, as well as hospital outcomes according to the AMI Register.Material and methods. 321 patients consecutively hospitalized in the Khabarovsk  Regional Vascular Center were included into AMI Register: 177 patients with ST-segment elevation AMI (STEMI; 55.1%; 135 patients non-ST-segment elevation AMI (non-STEMI; 42.1%; 9 patients with early recurrence of AMI and early post-infarction stenocardia (2.8%.Results. Before reference AMI a frequency of administration of statins was 13.7%, angiotensin-renin blockers – 29.3%, acetylsalicylic acid – 28.7%, beta-blocker – 25%. Among patients with atrial fibrillation only 7 ones (17% were treated with oral anticoagulants.        141 patients (79.6% with STEMI underwent PCI procedure: primary PCI – 82.3% and delayed PCI – 17.7%. PCI with coronary  stenting was performed  in 86.5% of patients with STEMI. Frequency  of PCI in non-STEMI patients was 42%: primary PCI – 43.9%, delayed PCI – 56.1%, PCI with coronary stenting – 43.9%. Gender and age of the patients did not influence the choice of tactics of revascularization in STEMI and non-STEMI (PCI(+, PCI(-, PCI with coronary  stenting (p<0.05.Medication in hospital: double antithrombotic therapy (DATT was prescribed in 86.9% of patients; direct anticoagulants – in 91.2%, statins – in 97.2%, beta-blockers – in 88.5%; renin-angiotensin-aldosterone system inhibitors – in 90.6%. A total lethality in STEMI was 15.2%, and in non-STEMI – 1.5%. Lethality in PCI-negative patients with STEMI was higher than  this in patients with non-STEMI (p<0.001. In STEMI patients lethality was 3.3  times lower in PCI-positive patients in comparison with PCI-negative patients.Conclusion. AMI Register demonstrated that before

  19. Single Agent Antihypertensive Therapy and Orthostatic Blood Pressure Behaviour in Older Adults Using Beat-to-Beat Measurements: The Irish Longitudinal Study on Ageing.

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    Mark Canney

    Full Text Available Impaired blood pressure (BP stabilisation after standing, defined using beat-to-beat measurements, has been shown to predict important health outcomes. We aimed to define the relationship between individual classes of antihypertensive agent and BP stabilisation among hypertensive older adults.Cross-sectional analysis from The Irish Longitudinal Study on Ageing, a cohort study of Irish adults aged 50 years and over. Beat-to-beat BP was recorded in participants undergoing an active stand test. We defined grade 1 hypertension according to European Society of Cardiology criteria (systolic BP [SBP] 140-159 mmHg ± diastolic BP [DBP] 90-99 mmHg. Outcomes were: (i initial orthostatic hypotension (IOH (SBP drop ≥40 mmHg ± DBP drop ≥20 mmHg within 15 seconds [s] of standing accompanied by symptoms; (ii sustained OH (SBP drop ≥20 mmHg ± DBP drop ≥10 mmHg from 60 to 110 s inclusive; (iii impaired BP stabilisation (SBP drop ≥20 mmHg ± DBP drop ≥10 mmHg at any 10 s interval during the test. Outcomes were assessed using multivariable-adjusted logistic regression.A total of 536 hypertensive participants were receiving monotherapy with a renin-angiotensin-aldosterone-system inhibitor (n = 317, 59.1%, beta-blocker (n = 89, 16.6%, calcium channel blocker (n = 89, 16.6% or diuretic (n = 41, 7.6%. A further 783 untreated participants met criteria for grade 1 hypertension. Beta-blockers were associated with increased odds of initial OH (OR 2.05, 95% CI 1.31-3.21 and sustained OH (OR 3.36, 95% CI 1.87-6.03 versus untreated grade 1 hypertension. Multivariable adjustment did not attenuate the results. Impaired BP stabilisation was evident at 20 s (OR 2.59, 95% CI 1.58-4.25 and persisted at 110 s (OR 2.90, 95% CI 1.64-5.11. No association was found between the other agents and any study outcome.Beta-blocker monotherapy was associated with a >2-fold increased odds of initial OH and a >3-fold increased odds of sustained OH and impaired BP stabilisation

  20. CHOICE OF THE INITIAL TREATMENT FOR MILD TO MODERATE ARTERIAL HYPERTENSION IN MOSCOW PRIMARY PRACTICE

    Directory of Open Access Journals (Sweden)

    S. V. Gatsura

    2015-09-01

    Full Text Available Aim. To assess the choice of initial pharmacotherapy of uncomplicated mild to moderate arterial hypertension (HT in Moscow primary care as well as to clear up the influence of regulatory measures on this choice.Material and methods. Results of two similar surveys conducted in 2011-2012 (452 respondents and 2013-2014 (273 respondents were compared to estimate preferences of Moscow primary care physicians regarding initial antihypertensive agents for therapy of uncomplicated mild to moderate HT taking into consideration an influence of regulatory requirement to prescribe medicinal products by international nonproprietary name (INN since July 2012. All participants were proposed to write down their preferred antihypertensive agents for initial mono- or combined therapy of mild to moderate HT with moderate cardiovascular risk and absence of compelling indications.Results. Angiotensin converting enzyme inhibitors (ACEI remained the leading class of antihypertensive agents, though their popularity slightly but significantly declined from 44.4% in 2011-12 to 37.2% in 2013-14 (р<0.05. Angiotensin receptor blockers partially displaced the leaders and increased their popularity from 11.3% in 2011-12 to 18.0% in 2013-14 (р<0.01. ACEI/diuretic combination remained on the 3rd position (16.4% and 15.3% respectively. Beta-blockers and diuretics as monotherapy shared 4th and 5th places in this rating. Calcium channel blockers popularity among Moscow prescribers remained unchanged and poor – 2.1%. The most popular medicine by trade name was Noliprel, perindopril/indapamide fixed combination, – 14.0% and 13.7% of respondents in 2011-12 and 2013-14, respectively. The share of medicine products recommended by INN went up from 11.9% to 22.8% among top-10 popular medications (р<0.01.Conclusion. Blockers of renin-angiotensin-aldosterone system remain the leading drugs for the initial treatment of uncomplicated mild to moderate HT without compelling indications

  1. Association analysis of ADPRT1, AKR1B1, RAGE, GFPT2 and PAI-1 gene polymorphisms with chronic renal insufficiency among Asian Indians with type-2 diabetes

    Directory of Open Access Journals (Sweden)

    Gupta Arvind

    2010-03-01

    Full Text Available Abstract Background To determine association of nine single nucleotide polymorphisms (SNPs in ADP ribosyltransferase-1 (ADPRT1, aldo-keto reductase family 1 member B1 (AKR1B1, receptor for advanced glycation end-products (RAGE, glutamine:fructose-6-phosphate amidotransferase-2 (GFPT2, and plasminogen activator inhibitor-1 (PAI-1 genes with chronic renal insufficiency (CRI among Asian Indians with type 2 diabetes; and to identify epistatic interactionss between genes from the present study and those from renin-angiotensin-aldosterone system (RAAS, and chemokine-cytokine, dopaminergic and oxidative stress pathways (previously investigated using the same sample set. Methods Type 2 diabetes subjects with CRI (serum creatinine ≥3.0 mg/dl constituted the cases (n = 196, and ethnicity and age matched individuals with diabetes for a duration of ≥ 10 years, normal renal functions and normoalbuminuria recruited as controls (n = 225. Allelic and genotypic constitution of 10 polymorphisms (SNPs from five genes namely- ADPRT1, AKR1B1, RAGE, GFPT2 and PAI-1 with diabetic CRI was investigated. The genetic associations were evaluated by computation of odds ratio and 95% confidence interval. Multiple logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study epistatic interactions between SNPs in different genes. Results Single nucleotide polymorphisms -429 T>C in RAGE and rs7725 C>T SNP in 3' UTR in GFPT2 gene showed a trend towards association with diabetic CRI. Investigation using miRBase statistical tool revealed that rs7725 in GFPT2 was a perfect target for predicted miRNA (hsa miR-378 suggesting the presence of the variant 'T' allele may result in an upregulation of GFPT2 contributing to diabetic renal complication. Epistatic interaction between SNPs in transforming growth factor TGF-β1 (investigated using the same sample set and reported elsewhere and GFPT2 genotype was observed. Conclusions

  2. Natural compounds as corrosion inhibitors for highly cycled systems

    Energy Technology Data Exchange (ETDEWEB)

    Quraishi, M.A.; Farooqi, I.H.; Saini, P.A. [Corrosion Research Lab., Aligarh (India)

    1999-11-01

    Strict environmental legislations have led to the development of green inhibitors in recent years. In continuation of the authors` research work on development of green inhibitors, they have investigated the aqueous extracts of three plants namely: Azadirachta indica, Punica Granatum and Momordica charantia as corrosion inhibitors for mild steel in 3% NaCl using weight loss and electrochemical methods. All the investigated compounds exhibited excellent corrosion inhibition properties comparable to that of HEDP. Azadirachta showed better scale inhibition effect than HEDP.

  3. "Mixed inhibitor-prodrug" as a new approach toward systemically active inhibitors of enkephalin-degrading enzymes.

    Science.gov (United States)

    Fournié-Zaluski, M C; Coric, P; Turcaud, S; Lucas, E; Noble, F; Maldonado, R; Roques, B P

    1992-06-26

    In order to evaluate the possible advantages of potentiating the effects of the endogenous enkephalins, to obtain analgesia without the serious drawbacks of morphine, it was essential to design systemically active compounds which inhibit the two metabolizing enzymes, aminopeptidase N (APN) and neutral endopeptidase 24.11 (NEP). A new concept combining the idea of "prodrug" and "mixed inhibitor" was therefore developed. Given the high efficiency of beta-mercaptoalkylamines as APN inhibitors and of N-(mercaptoacyl) amino acids as NEP inhibitors, compounds associating these molecules through disulfide or thioester bonds, which are known to increase lipophilicity and to favor passage across the blood-brain barrier, have been synthesized. An HPLC study indicated that the disulfide bridge was resistant to serum enzymes but was cleaved by brain membrane homogenates, suggesting that the active inhibitors were released in the central nervous system. The validity of the approach was verified by the efficient antinociceptive responses obtained in the hot plate test in mice after iv administration of disulfide-containing inhibitors (ED50s of from 4 to 26 mg/kg on the jump latency time). The analgesic potencies of the "mixed inhibitor-prodrug" RB 101 [H2NCH(CH2CH2SCH3)CH2SSCH2CH(CH2Ph)CONHCH( CH2Ph)COOCH2Ph] after iv administration were three times greater than those of a similar combined dose of its two constitutive moieties. The separation of the two diastereoisomers constituting RB 101 showed that the analgesia has a stereochemical dependence, the (S,S,S)-isomer being more active than the (S,R,S)-isomer. Furthermore, in the tail flick test in the rat, RB 101 gave 38% analgesia at a dose of 80 mg/kg. Due to its high efficiency and its longer pharmacological effect, RB 101 was selected for a complete study of its analgesic properties.

  4. HDAC Inhibitors as Epigenetic Regulators of the Immune System: Impacts on Cancer Therapy and Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Elizabeth E. Hull

    2016-01-01

    Full Text Available Histone deacetylase (HDAC inhibitors are powerful epigenetic regulators that have enormous therapeutic potential and have pleiotropic effects at the cellular and systemic levels. To date, HDAC inhibitors are used clinically for a wide variety of disorders ranging from hematopoietic malignancies to psychiatric disorders, are known to have anti-inflammatory properties, and are in clinical trials for several other diseases. In addition to influencing gene expression, HDAC enzymes also function as part of large, multisubunit complexes which have many nonhistone targets, alter signaling at the cellular and systemic levels, and result in divergent and cell-type specific effects. Thus, the effects of HDAC inhibitor treatment are too intricate to completely understand with current knowledge but the ability of HDAC inhibitors to modulate the immune system presents intriguing therapeutic possibilities. This review will explore the complexity of HDAC inhibitor treatment at the cellular and systemic levels and suggest strategies for effective use of HDAC inhibitors in biomedical research, focusing on the ability of HDAC inhibitors to modulate the immune system. The possibility of combining the documented anticancer effects and newly emerging immunomodulatory effects of HDAC inhibitors represents a promising new combinatorial therapeutic approach for HDAC inhibitor treatments.

  5. 21 CFR 866.5890 - Inter-alpha trypsin inhibitor immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Inter-alpha trypsin inhibitor immunological test system. 866.5890 Section 866.5890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5890 Inter-alpha trypsin inhibitor...

  6. Systemic and Brain Pharmacokinetics of Perforin Inhibitor Prodrugs

    DEFF Research Database (Denmark)

    Gynther, Mikko; Pickering, Darryl S; Spicer, Julie;

    2016-01-01

    We have recently reported that by converting a perforin inhibitor into an l-type amino acid transporter 1 (LAT1)-utilizing prodrug its cellular uptake can be greatly increased. The aim of the present study was to determine the in vivo and brain pharmacokinetics of two perforin inhibitors and thei......We have recently reported that by converting a perforin inhibitor into an l-type amino acid transporter 1 (LAT1)-utilizing prodrug its cellular uptake can be greatly increased. The aim of the present study was to determine the in vivo and brain pharmacokinetics of two perforin inhibitors...... and their LAT1-utilizing prodrugs 1 and 2. In addition, the brain uptake mechanism and entry into primary mouse cortical neurons and astrocytes were evaluated. After 23 μmol/kg i.p. bolus injection, the prodrugs’ unbound area under the concentration curve in brain was 0.3 nmol/g × min, whereas the parent drugs...... transporting polypeptides, probenecid, decreased the brain concentrations to 352.4 ± 44.5 and 70.9 ± 7.0 pmol/g, respectively. In addition, in vitro uptake studies showed that at 100 μM prodrug 1 had 3.4-fold and 4.5-fold higher uptake rate into neurons and astrocytes, respectively, compared to its parent drug...

  7. Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis

    Directory of Open Access Journals (Sweden)

    Mustata Gabriela

    2011-06-01

    Full Text Available Abstract Background The present study compares antiepileptic drugs and aromatase (CYP19 inhibitors for chemical and structural similarity. Human aromatase is well known as an important pharmacological target in anti-breast cancer therapy, but recent research demonstrates its role in epileptic seizures, as well. The current antiepileptic treatment methods cause severe side effects that endanger patient health and often preclude continued use. As a result, less toxic and more tolerable antiepileptic drugs (AEDs are needed, especially since every individual responds differently to given treatment options. Methods Through a pharmacophore search, this study shows that a model previously designed to search for new classes of aromatase inhibitors is able to identify antiepileptic drugs from the set of drugs approved by the Food and Drug Administration. Chemical and structural similarity analyses were performed using five potent AIs, and these studies returned a set of AEDs that the model identifies as hits. Results The pharmacophore model returned 73% (19 out of 26 of the drugs used specifically to treat epilepsy and approximately 82% (51 out of 62 of the compounds with anticonvulsant properties. Therefore, this study supports the possibility of identifying AEDs with a pharmacophore model that had originally been designed to identify new classes of aromatase inhibitors. Potential candidates for anticonvulsant therapy identified in this manner are also reported. Additionally, the chemical and structural similarity between antiepileptic compounds and aromatase inhibitors is proved using similarity analyses. Conclusions This study demonstrates that a pharmacophore search using a model based on aromatase inhibition and the enzyme's structural features can be used to screen for new candidates for antiepileptic therapy. In fact, potent aromatase inhibitors and current antiepileptic compounds display significant - over 70% - chemical and structural similarity

  8. Management of hypertension and heart failure in patients with Addison's disease.

    Science.gov (United States)

    Inder, Warrick J; Meyer, Caroline; Hunt, Penny J

    2015-06-01

    Addison's disease may be complicated by hypertension and less commonly by heart failure. We review the pathophysiology of the renin-angiotensin-aldosterone axis in Addison's disease and how this is altered in the setting of hypertension and heart failure. An essential first step in management in both conditions is optimizing glucocorticoid replacement and considering dose reduction if excessive. Following this, if a patient with Addison's disease remains hypertensive, the fludrocortisone dose should be reviewed and reduced if there are clinical and/or biochemical signs of mineralocorticoid excess. In the absence of such signs, where the renin is towards the upper end of the normal range or elevated, an angiotensin II (AII) receptor antagonist or angiotensin converting enzyme (ACE) inhibitor is the treatment of choice, and the fludrocortisone dose should remain unchanged. Dihydropyridine calcium channel blockers are clinically useful as second line agents, but diuretics should be avoided. In the setting of heart failure, there is an increase in total body sodium and water; therefore, it is appropriate to reduce and rarely consider ceasing the fludrocortisone. Loop diuretics may be used, but not aldosterone antagonists such as spironolactone or eplerenone. Standard treatment with ACE inhibitors, or as an alternative, AII receptor antagonists, are appropriate. Measurements of renin are no longer helpful in heart failure to determine the volume status but plasma levels of brain natriuretic peptide (BNP/proBNP) may help guide therapy. © 2014 John Wiley & Sons Ltd.

  9. A modular system to evaluate the efficacy of protease inhibitors against HIV-2.

    Directory of Open Access Journals (Sweden)

    Mohamed Mahdi

    Full Text Available The human immunodeficiency virus (HIV protease is a homodimeric aspartyl protease that is crucial for the viral life-cycle, cleaving proviral polyproteins, hence creating mature protein components that are required for the formation of an infectious virus. With diagnostic measures and clinically used protease inhibitors focusing on HIV-1, due to its higher virulence and prevalence, studies of the efficacy of those inhibitors on HIV-2 protease remain widely lacking. Utilizing a wild-type HIV-2 vector backbone and cloning techniques we have developed a cassette system where the efficacy of clinically used protease inhibitors can be studied for various serotypes of HIV-2 protease both in enzymatic and cell culture assays. In our experiments, optimization of the expression protocol led to a relatively stable enzyme, for cell culture assays, the efficiency of transfection and transduction capability of the modified vector was tested and was not found to differ from that of the wild-type, moreover, a 2nd generation protease inhibitor was used to demonstrate the usefulness of the system. The combination of assays performed with our cassette system is expected to provide an accurate measure of the efficacy of currently used; as well as experimental protease inhibitors on HIV-2.

  10. Reactive oxygen species: players in the cardiovascular effects of testosterone

    Science.gov (United States)

    Carneiro, Fernando S.; Carvalho, Maria Helena C.; Reckelhoff, Jane F.

    2015-01-01

    Androgens are essential for the development and maintenance of male reproductive tissues and sexual function and for overall health and well being. Testosterone, the predominant and most important androgen, not only affects the male reproductive system, but also influences the activity of many other organs. In the cardiovascular system, the actions of testosterone are still controversial, its effects ranging from protective to deleterious. While early studies showed that testosterone replacement therapy exerted beneficial effects on cardiovascular disease, some recent safety studies point to a positive association between endogenous and supraphysiological levels of androgens/testosterone and cardiovascular disease risk. Among the possible mechanisms involved in the actions of testosterone on the cardiovascular system, indirect actions (changes in the lipid profile, insulin sensitivity, and hemostatic mechanisms, modulation of the sympathetic nervous system and renin-angiotensin-aldosterone system), as well as direct actions (modulatory effects on proinflammatory enzymes, on the generation of reactive oxygen species, nitric oxide bioavailability, and on vasoconstrictor signaling pathways) have been reported. This mini-review focuses on evidence indicating that testosterone has prooxidative actions that may contribute to its deleterious actions in the cardiovascular system. The controversial effects of testosterone on ROS generation and oxidant status, both prooxidant and antioxidant, in the cardiovascular system and in cells and tissues of other systems are reviewed. PMID:26538238

  11. Liver cirrhosis and arterial hypertension

    Institute of Scientific and Technical Information of China (English)

    Jens H Henriksen; Soren Moller

    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 vasopressin),and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin, calcitonin generelated peptide, nitric oxide, and other vasodilators,and is most pronounced in the splanchnic area.This constitutes an effective (although relative)counterbalance to increased arterial blood pressure.This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most likely includes the combination of vasodilatation and vasoconstriction in parallel.

  12. [Organ Interactions: Heart and kidney].

    Science.gov (United States)

    Salleck, Daniel; John, Stefan

    2017-09-01

    The interactions between heart and kidney are various and of clinical relevance. Worsening of one organ often influences the function of the other. With NYHA and KDIGO we have classification systems for heart and kidney failure and those should be used for cardiorenal systems as well. Furthermore there is a useful classification system for cardiorenal syndromes itself. Cardiorenal syndrome is a complex illness which should be treated by interdisciplinary medical teams. A key roll in pathophysiology is the renin-angiotensin-aldosteron-system (RAAS). It's activation is followed by an increased salt and water retention as well as increased systemic an renal vasoconstriction leading to hypervolaemia an left ventricular hyperthrophy. General recommendations for the prevention of cardiovascular disease are good for the prevention of cardiorenal syndromes as well. RAAS-blockers should be used to stop cardial remodelling. A good regulation of hypertension and diabetes is important. Most important is a balanced intravasal volume. With volume overload negative balances can improve renal perfusion and therefor renal function. The furosemide stress test is a good cinical tool to check wether there is appropriate urine excretion and if volume overload can be treated by loop diuretics. Preload reduction can reduce cardiac output ahd renal function can be worsened especially in the beginning of overload-reduction. This may be acceptable. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Pronounced hypothermic synergy between systemic baclofen and NOS inhibitor.

    Science.gov (United States)

    Rawls, Scott M; Baron, David A; Gomez, Teresa; Jacobs, Kyle; Tallarida, Ronald J

    2004-10-19

    Baclofen was administered to rats systemically (intraperitoneal, i.p.) by itself or with L-NAME. Baclofen (1-7.5 mg/kg, i.p.) evoked dose-dependent hypothermia. L-NAME (50 mg/kg, i.p.) was ineffective. For combined administration, L-NAME increased the relative potency of baclofen (F=10.77, p<0.05), indicating multiplicative interaction and synergism. The present data reveal a surprising and significant interaction between nitric oxide synthase (NOS) and baclofen-induced hypothermia.

  14. Metabolic interactions of central nervous system medications and selective serotonin reuptake inhibitors.

    Science.gov (United States)

    Naranjo, C A; Sproule, B A; Knoke, D M

    1999-05-01

    Selective serotonin reuptake inhibitors (SSRIs) are prescribed alone and in combination with other psychotropic medications in the treatment of a variety of psychiatric disorders. Such combinations create the potential for pharmacokinetic interactions by affecting the activity of the cytochromes P450 (CYP450), drug metabolizing oxidative enzymes. SSRIs are not equivalent in their potential for interactions when combined with other central nervous system (CNS) medication. Generally citalopram and sertraline are characterized by weaker inhibition of CYP450 enzymes and, therefore, hold less potential for interaction than the other SSRIs. Paroxetine potently inhibits CYP2D6, which can result in increased neuroleptic serum concentrations, accompanied by increased CNS side-effects. Similarly, as a potent inhibitor of CYP2D6, fluoxetine can increase serum concentrations of neuroleptics and antidepressants and numerous case reports have documented concomitant adverse events. Fluoxetine also inhibits CYP3A and CYP2C19, increasing serum concentrations of some benzodiazepines. Fluvoxamine is a potent inhibitor of CYP1A2, a moderate inhibitor of CYP3A and a mild inhibitor of CYP2D6. Therefore, interactions with clozapine and benzodiazepines are evident.

  15. [Neuroendocrine changes in chronic cardiac insufficiency].

    Science.gov (United States)

    Jaeger, P; Cohen-Solal, A; Dahan, M; Juliard, J M; Charlier, P; Gourgon, R

    1988-02-01

    Throughout the course of chronic congestive heart failure cardiac and peripheral compensatory mechanisms are at play, most of them under the influence of the neuroendocrine system. The reserves of heart rate and contractility are regulated essentially by the noradrenergic system (NAS), but this mechanism is partial and transient owing to the gradual decrease in the density and sensitivity of myocardial beta-adrenergic receptors induced by overstimulation. Adaptation of the heart to exercise may be reduced. This escape phenomenon is also observed with almost all cardiotonic drugs which interfere with cyclic adenosine monophosphate (cAMP), in contrast with the paradoxically favourable effects of beta-blockers in small doses or of drugs that are both agonists and antagonists of beta-adrenergic receptors. The mechanisms which contribute to the induction of left ventricular hypertrophy are imperfectly known. The noradrenergic system and the renin-angiotensin-aldosterone system (RAAS) are probably not the only ones involved. The setting in action of Frank-Sterling heterometric regulation, at first during exercise then permanently, requires an increase in filling pressure obtained by venous constriction (predominantly controlled by the NAS) and, mostly, by an increase in circulating blood volume. NAS and RAAS intervene in the kidneys to produce water-and-salt retention.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Essential hypertension in adolescents and children: Recent advances in causative mechanisms

    Directory of Open Access Journals (Sweden)

    Manu Raj

    2011-01-01

    Full Text Available Essential hypertension is the most common form of hypertension in adults, and it is recognized more often in adolescents than in younger children. It is well known that the probability of a diagnosis of essential hypertension increases with age from birth onward. The initiation of high blood pressure burden starts in childhood and continues through adolescence to persist in the remaining phases of life. The genesis of essential hypertension is likely to be multifactorial. Obesity, insulin resistance, activation of sympathetic nervous system, sodium homeostasis, renin-angiotensin system, vascular smooth muscle structure and reactivity, serum uric acid levels, genetic factors and fetal programming have been implicated in this disorder. In addition, erythrocyte sodium transport, the free calcium concentration in platelets and leukocytes, urine kallikrein excretion, and sympathetic nervous system receptors have also been investigated as other possible mechanisms. Obesity in children appears to be the lead contributor of essential hypertension prevalence in children and adolescents. Suggested mechanisms of obesity-related hypertension include insulin resistance, sodium retention, increased sympathetic nervous system activity, activation of renin-angiotensin-aldosterone, and altered vascular function. The etiopathogenesis of essential hypertension in children and adolescents appears to closely resemble that of adults. The minor variations seen could probably be due to the evolving nature of this condition. Many of the established mechanisms that are confirmed in adult population need to be replicated in the pediatric age group by means of definitive research for a better understanding of this condition in future.

  17. The roles of sensitization and neuroplasticity in the long-term regulation of blood pressure and hypertension.

    Science.gov (United States)

    Johnson, Alan Kim; Zhang, Zhongming; Clayton, Sarah C; Beltz, Terry G; Hurley, Seth W; Thunhorst, Robert L; Xue, Baojian

    2015-12-01

    After decades of investigation, the causes of essential hypertension remain obscure. The contribution of the nervous system has been excluded by some on the basis that baroreceptor mechanisms maintain blood pressure only over the short term. However, this point of view ignores one of the most powerful contributions of the brain in maintaining biological fitness-specifically, the ability to promote adaptation of behavioral and physiological responses to cope with new challenges and maintain this new capacity through processes involving neuroplasticity. We present a body of recent findings demonstrating that prior, short-term challenges can induce persistent changes in the central nervous system to result in an enhanced blood pressure response to hypertension-eliciting stimuli. This sensitized hypertensinogenic state is maintained in the absence of the inducing stimuli, and it is accompanied by sustained upregulation of components of the brain renin-angiotensin-aldosterone system and other molecular changes recognized to be associated with central nervous system neuroplasticity. Although the heritability of hypertension is high, it is becoming increasingly clear that factors beyond just genes contribute to the etiology of this disease. Life experiences and attendant changes in cellular and molecular components in the neural network controlling sympathetic tone can enhance the hypertensive response to recurrent, sustained, or new stressors. Although the epigenetic mechanisms that allow the brain to be reprogrammed in the face of challenges to cardiovascular homeostasis can be adaptive, this capacity can also be maladaptive under conditions present in different evolutionary eras or ontogenetic periods.

  18. Renal neurohormonal regulation in heart failure decompensation.

    Science.gov (United States)

    Jönsson, Sofia; Agic, Mediha Becirovic; Narfström, Fredrik; Melville, Jacqueline M; Hultström, Michael

    2014-09-01

    Decompensation in heart failure occurs when the heart fails to balance venous return with cardiac output, leading to fluid congestion and contributing to mortality. Decompensated heart failure can cause acute kidney injury (AKI), which further increases mortality. Heart failure activates signaling systems that are deleterious to kidneys such as renal sympathetic nerve activity (RSNA), renin-angiotensin-aldosterone system, and vasopressin secretion. All three reduce renal blood flow (RBF) and increase tubular sodium reabsorption, which may increase renal oxygen consumption causing AKI through renal tissue hypoxia. Vasopressin contributes to venous congestion through aquaporin-mediated water retention. Additional water retention may be mediated through vasopressin-induced medullary urea transport and hyaluronan but needs further study. In addition, there are several systems that could protect the kidneys and reduce fluid retention such as natriuretic peptides, prostaglandins, and nitric oxide. However, the effect of natriuretic peptides and nitric oxide are blunted in decompensation, partly due to oxidative stress. This review considers how neurohormonal signaling in heart failure drives fluid retention by the kidneys and thus exacerbates decompensation. It further identifies areas where there is limited data, such as signaling systems 20-HETE, purines, endothelin, the role of renal water retention mechanisms for congestion, and renal hypoxia in AKI during heart failure.

  19. OBESITY-INDUCED HYPERTENSION: INTERACTION OF NEUROHUMORAL AND RENAL MECHANISMS

    Science.gov (United States)

    Hall, John E.; do Carmo, Jussara M.; da Silva, Alexandre A.; Wang, Zhen; Hall, Michael E.

    2015-01-01

    Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65–75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include 1) physical compression of the kidneys by fat in and around the kidneys, 2) activation of the renin-angiotensin-aldosterone system (RAAS), and 3) increased sympathetic nervous system (SNS) activity. Activation of the RAAS system is likely due, in part, to renal compression as well as SNS activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for SNS activation in obesity have not been fully elucidated but appear to require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes, and inflammation. Unless effective anti-obesity drugs are developed, the impact of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase. PMID:25767285

  20. Stress, depression and cardiovascular dysregulation: a review of neurobiological mechanisms and the integration of research from preclinical disease models.

    Science.gov (United States)

    Grippo, Angela J; Johnson, Alan Kim

    2009-01-01

    Bidirectional associations between mood disorders and cardiovascular diseases are extensively documented. However, the precise physiological and biochemical mechanisms that underlie such relationships are not well understood. This review focuses on the neurobiological processes and mediators that are common to both mood and cardiovascular disorders. The discussion places an emphasis on the role of exogenous stressors in addition to: (a) neuroendocrine and neurohumoral changes involving dysfunction of the hypothalamic-pituitary-adrenal axis and the activation of the renin-angiotensin-aldosterone system, (b) immune alterations including activation of pro-inflammatory cytokines, (c) autonomic and cardiovascular dysregulation including increased sympathetic drive, withdrawal of parasympathetic tone, cardiac rate and rhythm disturbances, and altered baroreceptor reflex function, (d) central neurotransmitter system dysfunction involving the dopamine, norepinephrine and serotonin systems, and (e) behavioral changes including fatigue and physical inactivity. The review also discusses experimental investigations using preclinical disease models to elucidate the neurobiological mechanisms underlying the link between mood disorders and cardiovascular disease. These include: (a) the chronic mild stress model of depression, (b) a model of congestive heart failure, (c) a model of cardiovascular deconditioning, (d) pharmacological manipulations of body fluid and sodium balance, and (e) pharmacological manipulations of the central serotonergic system. In combination with an extensive human research literature, the investigation of mechanisms underlying mood and cardiovascular regulation using animal models will enhance understanding the association between depression and cardiovascular disease. This will ultimately promote the development of better treatments and interventions for individuals with co-morbid psychological and somatic pathologies.

  1. Exercise training in hypertension: Role of microRNAs

    Institute of Scientific and Technical Information of China (English)

    Vander; José; das; Neves; Tiago; Fernandes; Fernanda; Roberta; Roque; Ursula; Paula; Renó; Soci; Stéphano; Freitas; Soares; Melo; Edilamar; Menezes; de; Oliveira

    2014-01-01

    Hypertension is a complex disease that constitutes an important public health problem and demands many studies in order to understand the molecular mechanisms involving his pathophysiology. Therefore, an increasing number of studies have been conducted and new therapies are continually being discovered. In this context, exercise training has emerged as an important non-pharmacological therapy to treat hypertensive patients, minimizing the side effects of pharmacological therapies and frequently contributing to allow pharmacotherapy to be suspended. Several mechanisms have been associated with the pathogenesis of hypertension, such as hyperactivity of the sympathetic nervous system and renin-angiotensin aldosterone system,impaired endothelial nitric oxide production, increased oxygen-reactive species, vascular thickening and stiffening, cardiac hypertrophy, impaired angiogenesis, and sometimes genetic predisposition. With the advent of microRNAs(miRNAs), new insights have been added to the perspectives for the treatment of this disease, and exercise training has been shown to be able to modulate the miRNAs associated with it. Elucidation of the relationship between exercise training and miRNAs in the pathogenesis of hypertension is fundamental in order to understand how exercise modulates the cardiovascular system at genetic level. This can be promising even for the development of new drugs. This article is a review of how exercise training acts on hypertension by means of specific miRNAs in the heart, vascular system, and skeletal muscle.

  2. Neurohumoral stimulation in type-2-diabetes as an emerging disease concept

    Directory of Open Access Journals (Sweden)

    Blüher M

    2004-03-01

    Full Text Available Abstract Neurohumoral stimulation comprising both autonomic-nervous-system dysfunction and activation of hormonal systems including the renin-angiotensin-aldosterone system (RAAS was found to be associated with Type-2-diabetes (T2D. Therapeutic strategies such as RAAS interference proved to be beneficial in both T2D treatment and prevention. In addition to an activated RAAS, hyperleptinemia in obesity, hyperinsulinemia in conditions of peripheral insulin resistance and overall oxidative stress in T2D represent known activators of the sympathetic component of the autonomic nervous system. Here, we hypothesize that sympathetic activation may cause peripheral insulin resistance defined as partial blocking of insulin effects on glucose uptake. Resulting hyperinsulinemia or hyperglycemia-related oxidative stress may further aggravate sympatho-excitation. This notion leads to a secondary hypothesis: sympathetic activation worsens from obesity towards insulin resistance, and further towards T2D. In this review, existing evidence relating to neurohumoral stimulation in T2D and consequences thereof, such as oxidative stress and inflammation, are discussed. The aim of this review is to provide a rationale for therapies, which are able to intercept neuroendocrine pathways in T2D and precursor states such as obesity.

  3. The Promise of Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease.

    Science.gov (United States)

    Griffin, Tomás P; Martin, William Patrick; Islam, Nahidul; O'Brien, Timothy; Griffin, Matthew D

    2016-05-01

    Diabetes mellitus (DM) commonly leads to progressive chronic kidney disease despite current best medical practice. The pathogenesis of diabetic kidney disease (DKD) involves a complex network of primary and secondary mechanisms with both intra-renal and systemic components. Apart from inhibition of the renin angiotensin aldosterone system, targeting individual pathogenic mediators with drug therapy has not, thus far, been proven to have high clinical value. Stem or progenitor cell therapies offer an alternative strategy for modulating complex disease processes through suppressing multiple pathogenic pathways and promoting pro-regenerative mechanisms. Mesenchymal stem cells (MSCs) have shown particular promise based on their accessibility from adult tissues and their diverse mechanisms of action including secretion of paracrine anti-inflammatory and cyto-protective factors. In this review, the progress toward clinical translation of MSC therapy for DKD is critically evaluated. Results from animal models suggest distinct potential for systemic MSC infusion to favourably modulate DKD progression. However, only a few early phase clinical trials have been initiated and efficacy in humans remains to be proven. Key knowledge gaps and research opportunities exist in this field. These include the need to gain greater understanding of in vivo mechanism of action, to identify quantifiable biomarkers of response to therapy and to define the optimal source, dose and timing of MSC administration. Given the rising prevalence of DM and DKD worldwide, continued progress toward harnessing the inherent regenerative functions of MSCs and other progenitor cells for even a subset of those affected has potential for profound societal benefits.

  4. New Insights on the Role of Vitamin D in the Progression of Renal Damage

    Directory of Open Access Journals (Sweden)

    Silvia Lucisano

    2013-12-01

    Full Text Available Several studies indicate a relationship between hypovitaminosis D, survival, vascular calcification and inflammation. In addition to its central role in the regulation of bone mineral metabolism, vitamin D also contributes to other systems, including the immune, cardiovascular and endocrine systems. Vitamin D analogs reduces proteinuria, in particular through suppression of the renin-angiotensin-aldosterone system (RAAS and exerts anti-inflammatory and immunomodulatory effects. In particular vitamin D deficiency contribute to an inappropriately activated RAAS, as a mechanism for progression of chronic kidney disease (CKD and/or cardiovascular disease. Human and sperimental models of CKD showed that vitamin D may interact with B and T lymphocytes and influence the phenotype and function of the antigen presenting cells and dendritic cells, promoting properties that favor the induction of tolerogenic T regulators rather than T effectory. Interstitial fibrosis may be prevented through vitamin D supplementation. Renal myofibroblast, an activated fibroblast with expression of a molecular hallmark α-smooth muscle actin (α-SMA, is generally considered the principal matrix-producing effector cells that are responsible for the excess production of extracellular matrix (ECM components in the fibrotic tissues. It turns out that calcitriol effectively blocks myofibroblast activation from interstitial fibroblasts, as evidenced by suppression of TGF-β1-mediated α-SMA expression.

  5. Cardiovascular Diseases and Fat Soluble Vitamins: Vitamin D and Vitamin K.

    Science.gov (United States)

    Tsugawa, Naoko

    2015-01-01

    Recently, the associations between insufficiency of fat soluble vitamins and cardiovascular diseases (CVDs) have been reported. Vitamin D affects the cardiovascular system via several pathways, such as suppression of parathyroid hormone, the renin- angiotensin-aldosterone system and vascular endothelial growth and the immune system. Cross-sectional and longitudinal studies have shown the association between the concentration of serum 25-hydroxyvitamin D (25OHD), which is a vitamin D metabolite indicating nutritional vitamin D status, and hypertension, myocardial infarction, heart failure and CVD mortality. On the other hand, the association between vitamin K status and CVDs, especially vascular calcification, has been also reported. Cross-sectional and cohort studies show that high vitamin K status is associated with reduced coronary artery calcification, CVDs and mortality risk. Epidemiological and basic studies indicate that vitamin K possesses a benefit in the prevention of the progression of coronary artery calcification via activation of matrix-gla protein (MGP). While these data in epidemiological and basic studies suggest the protective role of vitamin D and K in CVDs, the benefits of supplementation of both vitamins have not been validated in randomized controlled trials. Further basic and interventional studies are needed to confirm the benefit of both vitamins in protection against CVDs.

  6. Renal impairment and worsening of renal function in acute heart failure: can new therapies help? The potential role of serelaxin.

    Science.gov (United States)

    Schmieder, Roland E; Mitrovic, Veselin; Hengstenberg, Christian

    2015-08-01

    Renal dysfunction is a frequent finding in patients with acute heart failure (AHF) and an important prognostic factor for adverse outcomes. Worsening of renal function occurs in 30-50% of patients hospitalised for AHF, and is associated with increased mortality, prolonged hospital stay and increased risk of readmission. Likely mechanisms involved in the decrease in renal function include impaired haemodynamics and activation of neurohormonal factors, such as the renin-angiotensin-aldosterone system, the sympathetic nervous system and the arginine-vasopressin system. Additionally, many drugs currently used to treat AHF have a detrimental effect on renal function. Therefore, pharmacotherapy for AHF should carefully take into account any potential complications related to renal function. Serelaxin, currently in clinical development for the treatment of AHF is a recombinant form of human relaxin-2, identical in structure to the naturally occurring human relaxin-2 peptide hormone that mediates cardiac and renal adaptations during pregnancy. Data from both pre-clinical and clinical studies indicate a potentially beneficial effect of serelaxin on kidney function. In this review, we discuss the mechanisms and impact of impairment of renal function in AHF, and the potential benefits of new therapies, such as serelaxin, in this context.

  7. Maladaptive immune and inflammatory pathways lead to cardiovascular insulin resistance

    Science.gov (United States)

    Aroor, Annayya R.; McKarns, Susan; DeMarco, Vincent G.; Guanghong, Jia; Sowers, James R.

    2013-01-01

    Insulin resistance is a hallmark of obesity, the cardiorenal metabolic syndrome and type 2 diabetes mellitus (T2DM). The progression of insulin resistance increases the risk for cardiovascular disease (CVD). The significance of insulin resistance is underscored by the alarming rise in the prevalence of obesity and its associated comorbidities in the Unites States and worldwide over the last 40-50 years. The incidence of obesity is also on the rise in adolescents. Furthermore, premenopausal women have lower CVD risk compared to men, but this protection is lost in the setting of obesity and insulin resistance. Although systemic and cardiovascular insulin resistance are associated with impaired insulin metabolic signaling and cardiovascular dysfunction, the mechanisms underlying insulin resistance and cardiovascular dysfunction remain poorly understood. Recent studies show that insulin resistance in obesity and diabetes is linked to a metabolic inflammatory response, a state of systemic and tissue specific chronic low grade inflammation. Evidence is also emerging that there is polarization of macrophages and lymphocytes towards a pro-inflammatory phenotype that contribute to progression of insulin resistance in obesity, cardiorenal metabolic syndrome and diabetes. In this review, we provide new insights into factors, such as, the renin-angiotensin-aldosterone system, sympathetic activation and incretin modulators (e.g., DPP-4) and immune responses that mediate this inflammatory state in obesity and other conditions characterized by insulin resistance. PMID:23932846

  8. Obesity and cardiovascular risk in children and adolescents

    Directory of Open Access Journals (Sweden)

    Manu Raj

    2012-01-01

    Full Text Available The global prevalence of overweight and obesity in children and adolescents has increased substantially over the past several decades. These trends are also visible in developing economies like India. Childhood obesity impacts all the major organ systems of the body and is well known to result in significant morbidity and mortality. Obesity in childhood and adolescence is associated with established risk factors for cardiovascular diseases and accelerated atherosclerotic processes, including elevated blood pressure (BP, atherogenic dyslipidemia, atherosclerosis, metabolic syndrome, type II diabetes mellitus, cardiac structural and functional changes and obstructive sleep apnea. Probable mechanisms of obesity-related hypertension include insulin resistance, sodium retention, increased sympathetic nervous system activity, activation of the renin-angiotensin-aldosterone system and altered vascular function. Adiposity promotes cardiovascular risk clustering during childhood and adolescence. Insulin resistance has a strong association with childhood obesity. A variety of proinflammatory mediators that are associated with cardiometabolic dysfunction are also known to be influenced by obesity levels. Obesity in early life promotes atherosclerotic disease in vascular structures such as the aorta and the coronary arteries. Childhood and adolescent adiposity has strong influences on the structure and function of the heart, predominantly of the left ventricle. Obesity compromises pulmonary function and increases the risk of sleep-disordered breathing and obstructive sleep apnea. Neglecting childhood and adolescent obesity will compromise the cardiovascular health of the pediatric population and is likely to result in a serious public health crisis in future.

  9. Neuro-hormonal effects of physical activity in the elderly

    Directory of Open Access Journals (Sweden)

    Grazia Daniela eFemminella

    2013-12-01

    Full Text Available Thanks to diagnostic and therapeutic advances, the elderly population is continuously increasing in the western countries. Accordingly, the prevalence of most chronic age-related diseases will increase considerably in the next decades, thus it will be necessary to implement effective preventive measures to face this epidemiological challenge. Among those, physical activity exerts a crucial role, since it has been proven to reduce the risk of cardiovascular diseases, diabetes, obesity, cognitive impairment and cancer. The favourable effects of exercise on cardiovascular homeostasis can be at least in part ascribed to the modulation of the neuro-hormonal systems implicated in cardiovascular pathophysiology. In the elderly, exercise has been shown to affect catecholamine secretion and biosynthesis, to positively modulate the renin-angiotensin-aldosterone system and to reduce the levels of plasma brain natriuretic peptides. Moreover, drugs modulating the neuro-hormonal systems may favourably affect physical capacity in the elderly. Thus, efforts should be made to actually make physical activity become part of the therapeutic tools in the elderly.

  10. Neuro-hormonal effects of physical activity in the elderly.

    Science.gov (United States)

    Femminella, Grazia D; de Lucia, Claudio; Iacotucci, Paola; Formisano, Roberto; Petraglia, Laura; Allocca, Elena; Ratto, Enza; D'Amico, Loreta; Rengo, Carlo; Pagano, Gennaro; Bonaduce, Domenico; Rengo, Giuseppe; Ferrara, Nicola

    2013-12-20

    Thanks to diagnostic and therapeutic advances, the elderly population is continuously increasing in the western countries. Accordingly, the prevalence of most chronic age-related diseases will increase considerably in the next decades, thus it will be necessary to implement effective preventive measures to face this epidemiological challenge. Among those, physical activity exerts a crucial role, since it has been proven to reduce the risk of cardiovascular diseases, diabetes, obesity, cognitive impairment and cancer. The favorable effects of exercise on cardiovascular homeostasis can be at least in part ascribed to the modulation of the neuro-hormonal systems implicated in cardiovascular pathophysiology. In the elderly, exercise has been shown to affect catecholamine secretion and biosynthesis, to positively modulate the renin-angiotensin-aldosterone system and to reduce the levels of plasma brain natriuretic peptides. Moreover, drugs modulating the neuro-hormonal systems may favorably affect physical capacity in the elderly. Thus, efforts should be made to actually make physical activity become part of the therapeutic tools in the elderly.

  11. The Changing Role of Sodium Management in Cirrhosis.

    Science.gov (United States)

    Lizaola, Blanca; Bonder, Alan; Tapper, Elliot B; Mendez-Bocanegra, Angela; Cardenas, Andres

    2016-06-01

    Hyponatremia may occur in patients with cirrhosis and ascites mainly due to water retention and an inability of the kidney to excrete free water. The main reason for this abnormality is related to the fact that these patients have portal hypertension and this leads to systemic vasodilation that in turn activates sodium-retaining and water-retaining systems such as the renin-angiotensin-aldosterone system and arginine vasopressin (AVP). AVP increases solute-free water retention by acting on the V2 receptors of the kidney-collecting tubes. Hyponatremia in cirrhosis is defined as a serum sodium level less than 130 meq/L. The appearance of hyponatremia in patients with advanced cirrhosis portends a poor prognosis before and after liver transplantation. Treatment of hyponatremia is difficult; fluid restriction rarely increases serum sodium levels and other therapies are associated with important drawbacks. A thorough discussion of the underlying mechanisms leading to hyponatremia and hypernatremia in cirrhosis and current treatment options including the use of vaptans (V2 receptor antagonists) are discussed in this review.

  12. Obesity and insulin resistance in resistant hypertension: implications for the kidney.

    Science.gov (United States)

    Rao, Akhilesh; Pandya, Vishwam; Whaley-Connell, Adam

    2015-05-01

    There is recognition that the obesity epidemic contributes substantially to the increasing incidence of CKD and resistant hypertension (HTN). The mechanisms by which obesity promotes resistance are an area of active interest and intense investigation. It is thought that increases in visceral adiposity lead to a proinflammatory, pro-oxidative milieu that promote resistance to the metabolic actions of insulin. This resistance to insulin at the level of skeletal muscle tissue impairs glucose disposal/utilization through actions on the endothelium that include vascular rarefaction, reductions in vascular relaxation, and vascular remodeling. Insulin resistance derived from increased adipose tissue and obesity has system-wide implications for other tissue beds such as the kidney that affects blood pressure regulation. The additional autocrine and paracrine activities of adipose tissue contribute to inappropriate activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system that promote kidney microvascular remodeling, stiffness, and sodium (Na(+)) retention that in turn promote HTN and in the CKD patient, resistance. In this review, we will summarize the important mechanisms that link obesity to CKD as they relate to resistant HTN.

  13. Role of the Kidneys in Resistant Hypertension

    Directory of Open Access Journals (Sweden)

    Z. Khawaja

    2011-01-01

    Full Text Available Resistant hypertension is a failure to achieve goal BP (<140/90 mm Hg for the overall population and <130/80 mm Hg for those with diabetes mellitus or chronic kidney disease in a patient who adheres to maximum tolerated doses of 3 antihypertensive drugs including a diuretic. The kidneys play a critical role in long-term regulation of blood pressure. Blunted pressure natriuresis, with resultant increase in extracellular fluid volume, is an important cause of resistant hypertension. Activation of the renin-angiotensin-aldosterone system, increased renal sympathetic nervous system activity and increased sodium reabsorption are important renal mechanisms. Successful treatment requires identification and reversal of lifestyle factors or drugs contributing to treatment resistance, diagnosis and appropriate treatment of secondary causes of hypertension, use of effective multidrug regimens and optimization of diuretic therapy. Since inappropriate renal salt retention underlies most cases of drug-resistant hypertension, the therapeutic focus should be on improving salt depleting therapy by assessing and, if necessary, reducing dietary salt intake, optimizing diuretic therapy, and adding a mineralocorticoid antagonist if there are no contraindications.

  14. HEMODYNAMIC AND STRUCTURAL MODIFICATIONS IN CONTINUOUS INFUSION WITH ANGIOTENSIN. II. AN EXPERIMENTAL STUDY

    Directory of Open Access Journals (Sweden)

    Minela Aida Maranduca

    2011-09-01

    Full Text Available The renin-angiotensin-aldosterone system (RAAS is a hormonal system which contributes to the regulation of both arterial pressure and extra cellular fluids volume. The increase of RAAS, especially at angiotensin II (Ang II level, affects the target organs and increases the risk of cardio-vascular issues, by increasing arterial pressure and through the direct effect of Ang II upon the vascular endothelium and the renal and cardiac tissue. Ang II reduces the renal capacity of sodium excretion and initiates a set of events which increase arterial pressure. Increase of arterial pressure is necessary for re-establishing sodium excretion, being realized by the pressure-natriuresis relationship. Arterial hypertension affects the target organs (heart, kidneys and leads to a vicious circle which contributes to maintaining a high arterial pressure. Materials and Method: Male Wistar rats subjected on a normal diet, received either a sham operation (n=9 or continuous angiotensin II (Ang II infusion (300ng/kgc/ min subcutaneously, via mini pumps. Water ingestion and systolic blood pressure were measured for 14 days, after which the animals were sacrificed under anesthesia with ketamin, and the xylasin body weight, water ingestion, heart mass, right and left ventricular mass, right and left kidney mass were measured. Results: After 14 days of Ang II infusion, bodily weight decreased, systolic blood pressure increased, heart and left ventricular mass indexed to body weight were significantly enhanced compared with the sham group, and kidneys mass indexed to body weight was similar in the two groups.

  15. The Decrement of Hemoglobin Concentration with Angiotensin II Receptor Blocker Treatment Is Correlated with the Reduction of Albuminuria in Non-Diabetic Hypertensive Patients: Post-Hoc Analysis of ESPECIAL Trial.

    Directory of Open Access Journals (Sweden)

    Jung Nam An

    Full Text Available Blockade of the renin-angiotensin-aldosterone system exhibits a renoprotective effect; however, blockade of this system may also decrease hemoglobin (Hb and erythropoietin (EPO levels. We evaluated the correlation between reduced albuminuria and decreased hemoglobin concentrations after treatment with an angiotensin II receptor blocker (ARB. Two hundred forty-five non-diabetic hypertensive participants with established albuminuria and relatively preserved renal function were treated with an ARB (40 mg/day olmesartan for eight weeks. Subsequent changes in various clinical parameters, including Hb, EPO, and albuminuria, were analyzed following treatment. After the 8-week treatment with an ARB, Hb and EPO levels significantly decreased. Patients with a greater decrease in Hb exhibited a greater reduction in 24-hour urinary albumin excretion compared with patients with less of a decrease or no decrease in Hb, whereas no associations with a decline in renal function and EPO levels were noted. Multivariate logistic regression analysis demonstrated a correlation between the reduction of urine albumin excretion and the decrease in Hb levels (after natural logarithm transformation, adjusted odds ratio 1.76, 95% confidence interval 1.21-2.56, P = 0.003. Linear regression analysis also supported this positive correlation (Pearson correlation analysis; R = 0.24, P < 0.001. Decreased Hb concentrations following ARB treatment were positively correlated with reduced albuminuria in non-diabetic hypertensive patients, regardless of decreased blood pressure and EPO levels or renal function decline.

  16. Oxidative Stress in Hypertension: Role of the Kidney

    Science.gov (United States)

    Araujo, Magali

    2014-01-01

    Abstract Significance: Renal oxidative stress can be a cause, a consequence, or more often a potentiating factor for hypertension. Increased reactive oxygen species (ROS) in the kidney have been reported in multiple models of hypertension and related to renal vasoconstriction and alterations of renal function. Nicotinamide adenine dinucleotide phosphate oxidase is the central source of ROS in the hypertensive kidney, but a defective antioxidant system also can contribute. Recent Advances: Superoxide has been identified as the principal ROS implicated for vascular and tubular dysfunction, but hydrogen peroxide (H2O2) has been implicated in diminishing preglomerular vascular reactivity, and promoting medullary blood flow and pressure natriuresis in hypertensive animals. Critical Issues and Future Directions: Increased renal ROS have been implicated in renal vasoconstriction, renin release, activation of renal afferent nerves, augmented contraction, and myogenic responses of afferent arterioles, enhanced tubuloglomerular feedback, dysfunction of glomerular cells, and proteinuria. Inhibition of ROS with antioxidants, superoxide dismutase mimetics, or blockers of the renin-angiotensin-aldosterone system or genetic deletion of one of the components of the signaling cascade often attenuates or delays the onset of hypertension and preserves the renal structure and function. Novel approaches are required to dampen the renal oxidative stress pathways to reduced O2−• rather than H2O2 selectivity and/or to enhance the endogenous antioxidant pathways to susceptible subjects to prevent the development and renal-damaging effects of hypertension. Antioxid. Redox Signal. 20, 74–101. PMID:23472618

  17. Pathophysiology, diagnosis and clinical management of hepatorenal syndrome: from classic to new drugs.

    Science.gov (United States)

    Barbano, Biagio; Sardo, Liborio; Gigante, Antonietta; Gasperini, Maria Ludovica; Liberatori, Marta; Giraldi, Gianluca Di Lazzaro; Lacanna, Antonio; Amoroso, Antonio; Cianci, Rosario

    2014-01-01

    Advanced cirrhosis is frequently associated with renal dysfunction. Hepatorenal syndrome (HRS) is characterized by the occurrence of kidney injury in cirrhotic patients in the absence of other identifiable causes. HRS is classified in 2 different types. Type 1 is characterized by acute renal failure and rapid functional deterioration of other organs, usually related to a precipitating event. Type 2 is characterized by slowly progressive renal failure and refractory ascites. Advanced liver disease induces the progression of hemodynamic alterations such as arterial vasodilation of splanchnic circulation and impairment of cardiac function. The resulting ineffective circulating blood volume promotes the activation of both the renin-angiotensin-aldosterone and sympathetic nervous system, by an increase of antidiuretic hormone activity, in an attempt to restore volemia. Despite fluid retention, ascites and dilutional hyponatremia, renal function is often initially preserved by renal production of vasodilators. However, further insults can lead to an imbalance between systemic vasoconstriction and local renal vasodilation, resulting in progressive renal failure. Over the last decade, clinical strategies to prevent HRS have been improved by a better understanding of the natural history of renal failure in cirrhosis, resulting in a reduction of HRS prevalence in cirrhotic patients. Vasoconstrictor drugs may improve renal function, but the effect on mortality has not yet been established. Vaptans, nonpeptide vasopressin receptor antagonists, may also reduce hyponatraemia and ascites, even if the clinical effects in HRS remain unknown. This review updates the pathophysiology, diagnosis and management of HRS.

  18. Hypertension: physiology and pathophysiology.

    Science.gov (United States)

    Hall, John E; Granger, Joey P; do Carmo, Jussara M; da Silva, Alexandre A; Dubinion, John; George, Eric; Hamza, Shereen; Speed, Joshua; Hall, Michael E

    2012-10-01

    Despite major advances in understanding the pathophysiology of hypertension and availability of effective and safe antihypertensive drugs, suboptimal blood pressure (BP) control is still the most important risk factor for cardiovascular mortality and is globally responsible for more than 7 million deaths annually. Short-term and long-term BP regulation involve the integrated actions of multiple cardiovascular, renal, neural, endocrine, and local tissue control systems. Clinical and experimental observations strongly support a central role for the kidneys in the long-term regulation of BP, and abnormal renal-pressure natriuresis is present in all forms of chronic hypertension. Impaired renal-pressure natriuresis and chronic hypertension can be caused by intrarenal or extrarenal factors that reduce glomerular filtration rate or increase renal tubular reabsorption of salt and water; these factors include excessive activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, increased formation of reactive oxygen species, endothelin, and inflammatory cytokines, or decreased synthesis of nitric oxide and various natriuretic factors. In human primary (essential) hypertension, the precise causes of impaired renal function are not completely understood, although excessive weight gain and dietary factors appear to play a major role since hypertension is rare in nonobese hunter-gathers living in nonindustrialized societies. Recent advances in genetics offer opportunities to discover gene-environment interactions that may also contribute to hypertension, although success thus far has been limited mainly to identification of rare monogenic forms of hypertension. © 2012 American Physiological Society

  19. Mechanistic approach to the pathophysiology of target organ damage in hypertension from studies in a human model with characteristics opposite to hypertension: Bartter's and Gitelman's syndromes.

    Science.gov (United States)

    Calò, L A; Maiolino, G

    2015-07-01

    Extensive studies using Bartter's/Gitelman's syndrome patients have provided insights into the angiotensin II (Ang II) signaling pathways involved in the regulation of vascular tone and cardiovascular-renal remodeling. The renin-angiotensin-aldosterone system is activated in these syndromes, however, patients do not develop hypertension and cardiovascular remodeling and clinically manifest conditions opposite to hypertension. The short- and the long-term signaling of Ang II remains an important matter of investigation to shed light on mechanisms responsible for the pathophysiology of hypertension and its long-term complications. The long-term signaling of Ang II is involved in the pathophysiology of cardiovascular-renal remodeling and inflammatory responses in which the balance between RhoA/Rho kinase pathway and NO system plays a crucial role. In this brief review, the results of our studies in Bartter's and Gitelman's syndromes are reported on these processes. The information obtained from these studies can clarify, confirm or be used to extend the biochemical mechanisms responsible for the pathophysiology of hypertension and its long-term complications and could offer further chances to identify additional potential significant targets of therapy.

  20. Review article: eplerenone: an underused medication?

    Science.gov (United States)

    Abuannadi, Mohammad; O'Keefe, James H

    2010-12-01

    In this article, we review the evidence supporting the use of eplerenone for improving cardiovascular prognosis. Activation of the renin-angiotensin-aldosterone system plays a major role in the pathogenesis of heart disease, and blockage of this system has been shown to improve prognosis in several cardiovascular conditions. The 2 marketed aldosterone antagonists, spironolactone and eplerenone, improve prognosis in patients with left ventricular (LV) dysfunction and are effective antihypertensive medications. In addition, a potential role for aldosterone antagonists in the treatment of patients with heart failure and preserved LV function has been suggested and is currently being evaluated in clinical trials. In patients with myocardial infarction having LV dysfunction and evidence of heart failure, eplerenone improves cardiovascular outcomes and attenuates myocardial remodeling. In addition, eplerenone is effective for the treatment of hypertension, where it regresses both LV hypertrophy and proteinuria (2 powerful markers of increased cardiovascular risk). In contrast to spironolactone, eplerenone essentially lacks the sexual side effects that sometimes limit the use of spironolactone. Hyperkalemia is the main potential side effect of eplerenone, especially when used in combination with other medications that can cause hyperkalemia. Adequate patient selection and monitoring are therefore of utmost importance when using this medication. In conclusion, eplerenone is a medication that offers the cardiovascular therapeutic and prognostic benefits of aldosterone antagonism but with fewer side effects compared to spironolactone.

  1. 脑钠肽在儿童心血管疾病诊治中的研究进展%Research advance of brain natriuretic peptide in the diagnosis and treatment of pediatric cardiovascular disease

    Institute of Scientific and Technical Information of China (English)

    吴利伟(综述); 王凤鸣(审校)

    2013-01-01

      脑钠肽(BNP)是一种主要来源于心室的心脏内分泌激素,具有很强的利钠、利尿、扩张血管、抑制肾素–血管紧张素–醛固酮系统(RAAS)和交感神经系统活性作用。研究表明,心血管疾病患儿的血浆BNP及氨基末端脑钠肽原(NT-proBNP)水平升高,可以反映心室功能变化。该文就BNP/NT-proBNP的生物学特性、检测方法、正常值范围及其在儿童心血管疾病诊治中的研究进展作一综述。%Brain natriuretic peptide(BNP) is a cardiac hormone mainly secreted by myocytes in the ventricular wall. It has strong action of natriuresis, diuresis, vasodilation, inhibition of renin-angiotensin-aldosterone system and sympathetic nervous system. The increased levels of BNP and NT-proBNP have been reported in children’s cardiovascular diseases in numerous stu-dies and can reflect cardiac function. This article simply reviews the BNP and NT-proBNP about its biology character, detection method, medical reference range and its progress in pediatric cardiovascular disease.

  2. 脑钠肽在儿科疾病的应用%The use of brain natriuretic peptide in pediatric diseases

    Institute of Scientific and Technical Information of China (English)

    章阿元

    2015-01-01

    脑钠肽(brain natriuretic peptide,BNP)是利钠肽家族中的一员,主要由心室肌细胞分泌,有利钠、利尿、扩张血管、抑制肾素-血管紧张素-醛固酮系统和交感神经系统活性作用.近年来,BNP检测多用于成人疾病领域,尤其是其在心血管疾病的临床应用已形成广泛共识.但目前BNP在儿科领域的相关研究及应用仍相对较少,本文就目前BNP在儿科领域的研究现状作一综述.%Brain natriuretic peptide (BNP) is one member of natriuretic peptide family and mainly secreted by ventricular myocardium.BNP has many functions such as natriuresis,diuresis,dilation of blood vessels,inhibition of renin-angiotensin-aldosterone system and sympathetic nervous system activity.In recent years,BNP analysis widely used in fields of adult diseases,especially in cardiovascular disease.But research and application of BNP in pediatrics diseases is still relatively small.This article reviewed biology character and the progress of BNP in pediatric diseases.

  3. MicroRNA and Heart Failure

    Directory of Open Access Journals (Sweden)

    Lee Lee Wong

    2016-04-01

    Full Text Available Heart failure (HF imposes significant economic and public health burdens upon modern society. It is known that disturbances in neurohormonal status play an important role in the pathogenesis of HF. Therapeutics that antagonize selected neurohormonal pathways, specifically the renin-angiotensin-aldosterone and sympathetic nervous systems, have significantly improved patient outcomes in HF. Nevertheless, mortality remains high with about 50% of HF patients dying within five years of diagnosis thus mandating ongoing efforts to improve HF management. The discovery of short noncoding microRNAs (miRNAs and our increasing understanding of their functions, has presented potential therapeutic applications in complex diseases, including HF. Results from several genome-wide miRNA studies have identified miRNAs differentially expressed in HF cohorts suggesting their possible involvement in the pathogenesis of HF and their potential as both biomarkers and as therapeutic targets. Unravelling the functional relevance of miRNAs within pathogenic pathways is a major challenge in cardiovascular research. In this article, we provide an overview of the role of miRNAs in the cardiovascular system. We highlight several HF-related miRNAs reported from selected cohorts and review their putative roles in neurohormonal signaling.

  4. Effects of β-adrenoceptor subtypes on cardiac function in myocardial infarction rats exposed to fine particulate matter (PM 2.5).

    Science.gov (United States)

    Gao, Yuping; Lv, Jiyuan; Lin, Yuanyuan; Li, Xuewen; Wang, Lixia; Yin, Yanping; Liu, Yan

    2014-01-01

    The pathophysiological mechanisms of heart failure (HF) stems were mainly from longstanding overactivation of the sympathetic nervous system and renin-angiotensin-aldosterone system. Recent studies highlighted the potential benefits of β1-adrenoceptor (β1-AR) blocker combined with β2-adrenergic receptor (β2-AR) agonist in patients with HF. Long-term exposure to fine particulate air pollution, such as particulate matter ≤ 2.5 μm in diameter (PM2.5), has been found associated with acute myocardial infarction (AMI) which is the most common cause of congestive HF. In this study, we have investigated the effect of combined metoprolol and terbutaline on cardiac function in a rat model of AMI exposed to PM2.5. Our results demonstrated that short-term exposure to PM2.5 contributes to aggravate cardiac function in rats with myocardial infarction. The combined use of β1-AR blocker and β2-AR agonist is superior to β1-AR blocker alone for the treatment of AMI rats exposed to PM2.5. The combination of β1-AR blocker and β2-AR agonist may decrease the mortality of patients with myocardial infarction who have been exposed to PM2.5.

  5. Effects of β-Adrenoceptor Subtypes on Cardiac Function in Myocardial Infarction Rats Exposed to Fine Particulate Matter (PM2.5

    Directory of Open Access Journals (Sweden)

    Yuping Gao

    2014-01-01

    Full Text Available The pathophysiological mechanisms of heart failure (HF stems were mainly from longstanding overactivation of the sympathetic nervous system and renin-angiotensin-aldosterone system. Recent studies highlighted the potential benefits of β1-adrenoceptor (β1-AR blocker combined with β2-adrenergic receptor (β2-AR agonist in patients with HF. Long-term exposure to fine particulate air pollution, such as particulate matter ≤ 2.5 μm in diameter (PM2.5, has been found associated with acute myocardial infarction (AMI which is the most common cause of congestive HF. In this study, we have investigated the effect of combined metoprolol and terbutaline on cardiac function in a rat model of AMI exposed to PM2.5. Our results demonstrated that short-term exposure to PM2.5 contributes to aggravate cardiac function in rats with myocardial infarction. The combined use of β1-AR blocker and β2-AR agonist is superior to β1-AR blocker alone for the treatment of AMI rats exposed to PM2.5. The combination of β1-AR blocker and β2-AR agonist may decrease the mortality of patients with myocardial infarction who have been exposed to PM2.5.

  6. Changes in peritoneal membrane permeability and proteinuria in patients on peritoneal dialysis after treatment with paricalcitol − a preliminary study.

    Science.gov (United States)

    Coronel, Francisco; Cigarran, Secundino; Gomis, Antonio; Rodríguez-Cubillo, Beatriz; Herrero, José Antonio; Delgado, Pablo; Delgado, Jesus

    2012-08-01

    Patients on peritoneal dialysis (PD) have protein loss through peritoneal membrane (PM) and experience changes in permeability of the membrane. Paricalcitol is a selective vitamin D receptor activator with an effect upon systemic inflammation and an inhibitory effect upon the renin-angiotensin-aldosterone system (RAAS). This study explores the possible effect of paricalcitol upon the PM in 23 patients on PD with high iPTH levels. Peritoneal kinetic studies were performed before and after paricalcitol, measuring also ultrafiltration/ day, peritoneal protein losses and proteinuria. Results were compared with a control group of 15 patients not receiving any form of vitamin D. With a mean dose of 1.3 μg/day, peritoneal protein loss decreased from 0.91 ± 0.35 to 0.76 ± 0.26 g/l (15.4%) (p = 0.007) and from 7.55 to 6.46 g/d (p permeability and proteinuria were found. The results of the study indicate that paricalcitol is effective in treating hyperparathyroidism in patients on PD, and suggest an effect upon proteinuria and PM permeability (not previously reported), with diminished peritoneal protein loss and increased ultrafiltration. The antiinflammatory, antifibrotic and RAAS-modulating actions described for paricalcitol may be responsible for these findings, and could be important for preserving the peritoneum as a dialyzing membrane.

  7. New therapeutic agents in diabetic nephropathy

    Science.gov (United States)

    Kim, Yaeni; Park, Cheol Whee

    2017-01-01

    Studies investigating diabetic nephropathy (DN) have mostly focused on interpreting the pathologic molecular mechanisms of DN, which may provide valuable tools for early diagnosis and prevention of disease onset and progression. Currently, there are few therapeutic drugs for DN, which mainly consist of antihypertensive and antiproteinuric measures that arise from strict renin-angiotensin-aldosterone system inactivation. However, these traditional therapies are suboptimal and there is a clear, unmet need for treatments that offer effective schemes beyond glucose control. The complexity and heterogeneity of the DN entity, along with ambiguous renal endpoints that may deter accurate appraisal of new drug potency, contribute to a worsening of the situation. To address these issues, current research into original therapies to treat DN is focusing on the intrinsic renal pathways that intervene with intracellular signaling of anti-inflammatory, antifibrotic, and metabolic pathways. Mounting evidence in support of the favorable metabolic effects of these novel agents with respect to the renal aspects of DN supports the likelihood of systemic beneficial effects as well. Thus, when translated into clinical use, these novel agents would also address the comorbid factors associated with diabetes, such as obesity and risk of cardiovascular disease. This review will provide a discussion of the promising and effective therapeutic agents for the management of DN. PMID:28049280

  8. Effect on manganese exposure on blood prolactin and plasma renin activity%锰接触对血中催乳素和血浆肾素活性的影响

    Institute of Scientific and Technical Information of China (English)

    牛侨; 何淑嫦; 陈艺兰; 代伏英; 王建英; 李怀应

    2001-01-01

    采用放射免疫的方法测定锰作业工人血中催乳素和血浆肾素活性,以探讨锰对内分泌和循环系统的影响。结果表明:锰接触组的血中催乳素浓度、肾素活性均明显高于对照组,提示锰接触可能影响结节-漏斗部位的功能,锰还可通过肾素-血管紧张素-醛固酮系统影响循环系统功能。%In order to study the adverse effects of manganese onneuro-endocrine and cardiovascular system, radioimmunoassay(RIA) was used to test the blood prolactin concentration and plasma renin activity among manganese-exposed workers The result showed that the blood prolactin concentration and Plasma renin activity in manganese exposed workers were significantly higher than those of control group.It suggested that manganese exposure might affect the function at tubero-infundibular area and renin-angiotensin aldosterone system.

  9. Reversible hyporeninemic hypoaldosteronism in a patient with tetraplegia.

    Science.gov (United States)

    Inaba, M; Katayama, S; Omoto, A; Maruno, Y; Itabashi, A; Ishii, J; Morimoto, S

    1989-02-01

    A 66-year-old man with tetraplegia developed hyperkalemia. Hyporeninemic hypoaldosteronism was disclosed on the basis of a lack of response of plasma renin activity to furosemide administration or tilting with marked hypotension and a subnormal response of aldosterone to furosemide stimulation, tilting, angiotensin II infusion and ACTH administration, as well as increased vascular responsiveness to angiotensin II infusion. Of interest was the finding that urinary excretion of epinephrine and norepinephrine was markedly reduced, indicating that hyporeninemia may possibly be due to a chronic lack of sympathetic nervous stimuli. The patient was treated with sodium polystyrene sulfonate resin and/or 9-alpha-fluorohydrocortisone, and wheelchair rehabilitation. However, even after stopping 8-month-mineralcorticoid replacement, normokalemia was maintained. Reexamination of the renin-angiotensin-aldosterone system revealed a normalized response to tilting or ACTH administration along with the normal catecholamine excretion. One more point to be noted is that ACTH administration resulted in a rise in the plasma levels of cortisol, corticosterone and 18-OH-corticosterone, but not aldosterone. This may be attributed to ACTH-stimulated 18-OH-corticosterone derived from the zona fasciculata or alternatively to a partial defect of corticosterone methyl oxidase type II (18-dehydrogenase) in the adrenal glomerulosa cells. These results suggested that hyporeninemic hypoaldosteronism may have been attributable to a decrease in systemic nervous stimuli and that such abnormalities were reversible.

  10. Novel strategies: challenge loop diuretics and sodium management in heart failure--Part I.

    Science.gov (United States)

    Pasquale, Pietro Di; Sarullo, Filippo M; Paterna, Salvatorew

    2007-01-01

    This is the first of a 2-part series. This article reviews the relationships among diuretics, neurohormonal activation, renal function, fluid and Na management, the cardiorenal syndrome, and heart failure. Part II will describe novel therapies based on these relationships, focusing particularly on vasopressin antagonists and treatment using hypertonic saline solution with high-dose loop diuretics. Heart failure (HF) is a complex hemodynamic disorder characterized by chronic and progressive pump failure and fluid accumulation. Diuretics are a vital component of symptomatic management, and enhancing diuretic response in the setting of diuretic resistance is therefore pivotal. In HF patients treated with diuretics, compensatory pathophysiologic mechanisms to maintain vascular resistance, such as nonosmotic stimulation of vasopressin secretion and activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, promote renal Na and water reabsorption. Thus, there remains a need to develop novel therapies for HF patients who are refractory to conventional medical treatment. The conflicting results of diuretic treatments in HF and the importance of Na management in the context of the cardiorenal syndrome and neurohormonal activation have suggested novel and counterintuitive strategies, focusing primarily on the use of vasopressin antagonists and hypertonic saline solution with high doses of loop diuretics and neurohormonal interference. The authors review the current evidence for these therapies and suggest hypothetical bases for their efficacy.

  11. Obesity-related hypertension: possible pathophysiological mechanisms.

    Science.gov (United States)

    Vaněčková, Ivana; Maletínská, Lenka; Behuliak, Michal; Nagelová, Veronika; Zicha, Josef; Kuneš, Jaroslav

    2014-12-01

    Hypertension is one of the major risk factors of cardiovascular diseases, but despite a century of clinical and basic research, the discrete etiology of this disease is still not fully understood. The same is true for obesity, which is recognized as a major global epidemic health problem nowadays. Obesity is associated with an increasing prevalence of the metabolic syndrome, a cluster of risk factors including hypertension, abdominal obesity, dyslipidemia, and hyperglycemia. Epidemiological studies have shown that excess weight gain predicts future development of hypertension, and the relationship between BMI and blood pressure (BP) appears to be almost linear in different populations. There is no doubt that obesity-related hypertension is a multifactorial and polygenic trait, and multiple potential pathogenetic mechanisms probably contribute to the development of higher BP in obese humans. These include hyperinsulinemia, activation of the renin-angiotensin-aldosterone system, sympathetic nervous system stimulation, abnormal levels of certain adipokines such as leptin, or cytokines acting at the vascular endothelial level. Moreover, some genetic and epigenetic mechanisms are also in play. Although the full manifestation of both hypertension and obesity occurs predominantly in adulthood, their roots can be traced back to early ontogeny. The detailed knowledge of alterations occurring in the organism of experimental animals during particular critical periods (developmental windows) could help to solve this phenomenon in humans and might facilitate the age-specific prevention of human obesity-related hypertension. In addition, better understanding of particular pathophysiological mechanisms might be useful in so-called personalized medicine.

  12. The Cysteine Protease–Cysteine Protease Inhibitor System Explored in Soybean Nodule Development

    Directory of Open Access Journals (Sweden)

    Marian Dorcas Quain

    2013-08-01

    Full Text Available Almost all protease families have been associated with plant development, particularly senescence, which is the final developmental stage of every organ before cell death. Proteolysis remobilizes and recycles nitrogen from senescent organs that is required, for example, seed development. Senescence-associated expression of proteases has recently been characterized using large-scale gene expression analysis seeking to identify and characterize senescence-related genes. Increasing activities of proteolytic enzymes, particularly cysteine proteases, are observed during the senescence of legume nodules, in which a symbiotic relationship between the host plant and bacteria (Rhizobia facilitate the fixation of atmospheric nitrogen. It is generally considered that cysteine proteases are compartmentalized to prevent uncontrolled proteolysis in nitrogen-fixing nodules. In addition, the activities of cysteine proteases are regulated by endogenous cysteine protease inhibitors called cystatins. These small proteins form reversible complexes with cysteine proteases, leading to inactivation. However, very little is currently known about how the cysteine protease-cysteine protease inhibitor (cystatin system is regulated during nodule development. Moreover, our current understanding of the expression and functions of proteases and protease inhibitors in nodules is fragmented. To address this issue, we have summarized the current knowledge and techniques used for studying proteases and their inhibitors including the application of “omics” tools, with a particular focus on changes in the cysteine protease-cystatin system during nodule development.

  13. Vitamin D3 deficiency increases DNA damage and modify the expression of genes associated with hypertension in normotensive and hypertensive rats

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    Carla Silva Machado

    2015-05-01

    Full Text Available Vitamin D3 is a lipophilic micronutrient obtained from the diet (salmon, sardines, mackerel and cod liver oil or by the conversion of 7-dehydrocholesterol on skin after exposure to UVB radiation. This vitamin participates in several cellular processes, contributes to the maintenance of calcium concentrations, acts on phosphorus absorption, and is also related to the development and progression of chronic diseases. In hypertension, it is known that vitamin D3 act on renin-angiotensin-aldosterone system, regulates the gene expression and can induce or attenuate oxidative DNA damage. Vitamin D3 deficiency is present in 30-50% of human population (Pilz et al., 2009, and has been associated with increase of chromosomal instability and DNA damage (Nair-Shalliker; Armstrong; Fenech, 2012. Since experimental and clinical studies have suggested a relationship between vitamin D3 and blood pressure, the aim of this study was to evaluate whether vitamin D3 deficiency or supplementation lead to an increase or decrease in DNA damage, regulates the expression of genes associated with hypertension and changes the systolic blood pressure. Spontaneously hypertensive rats (SHR, used as a model of human essential hypertension, and their normotensive controls (Wistar Kyoto – WKY were fed a control diet (vitamin D3 at 1.000 UI/kg, a deficient diet (vitamin D3 at 0 UI/kg or a supplemented diet (vitamin D3 at 10.000 UI/kg for 12 weeks. DNA damage was assessed by comet assay in cardiac muscle tissue and blood tissue, following the methodology proposed by Singh et al. (1988 and Tice et al. (2000; gene expression of 84 genes was assessed by RT2ProfilerTM PCR Array in cardiac muscle tissue; and systolic blood pressure was measured weekly by a noninvasive method using tail plethysmography. In SHR and WKY rats, vitamin D3 deficiency increased DNA damage in the blood tissue and did not change the DNA damage in cardiac muscle tissue; vitamin D3 supplementation maintained the

  14. Association between Angiotensin I-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of Kidney Transplantation: A Meta-Analysis.

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    Zhengkai Huang

    Full Text Available Angiotensin I-converting enzyme (ACE is crucial in the renin-angiotensin-aldosterone system. ACE insertion/deletion (I/D polymorphism is a common genetic variation of this gene and is associated with several disease phenotypes. However, the results of published studies on the influence of this polymorphism on renal transplantation are inconsistent. Therefore, a meta-analysis was performed to evaluate the association between ACE I/D polymorphism and prognosis of kidney transplantation.A meta-analysis was performed based on 21 case-control studies from 12 publications (1497 cases and 2029 controls and 10 studies with quantitative values from 5 publications (814 patients. Pooled odds ratios (ORs and weighted mean differences (WMDs with their corresponding 95% confidence intervals (CIs were used to estimate associations.ACE I/D polymorphism was found to be associated with acute rejection (AR in genotypes DD+ID versus II (OR = 1.62, 95% CI = 1.14-2.29 and with serum creatinine concentration after renal transplantation in genotypes DD versus ID (WMD = 13.12, 95% CI = 8.09-18.16. Stratified analysis revealed that recipients transplanted within a year had higher serum creatinine concentrations in the DD versus ID model. No significant association was found between hypertension and ACE I/D polymorphism.ACE I/D polymorphism is associated with AR and allograft function after kidney transplantation.

  15. Renal artery stenosis: Up-date on diagnosis and treatment.

    Science.gov (United States)

    Zeller, Thomas; Macharzina, Roland; Rastan, Aljoscha; Beschorner, Ulrich; Noory, Elias

    2014-01-01

    Significant renal artery stenosis (RAS) can cause or result in deterioration of arterial hypertension and may promote the development of renal insufficiency. The activation of the renin-angiotensin-aldosterone system results in structural heart disease and may impact patient survival. Technical improvements of diagnostic and interventional endovascular tools have led to a more widespread use of endoluminal renal artery revascularization and extension of the indications for this type of therapy during the past two decades. Whereas balloon angioplasty is still the method of choice for the treatment of fibromuscular dysplasia, stent implantation is indicated in ostial atherosclerotic RAS. However, none of the so far published or presented randomized controlled trials could prove a beneficial outcome of RAS revascularization compared to medical management. As a result of these negative trials including the largest published trial to date, the ASTRAL trial, referrals to endovascular renal artery revascularization have declined and, moreover, reimbursement of these procedures has become a matter of debate. Crucial for a clinical benefit following revascularization of RAS is proper patient selection, revascularization being only indicated after proof of hemodynamic relevance of RAS. This article summarizes the appropriate diagnostic work-up of patients with suspected RAS, discusses the limitations of the results published so far and their impact on the indication for RAS revascularization.

  16. A randomized, double-blind trial comparing the effects of amlodipine besylate/benazepril HCl vs amlodipine on endothelial function and blood pressure.

    Science.gov (United States)

    Mohler, Emile R; Herrington, David; Ouyang, Pamela; Mangano, Charles; Ritter, Susan; Davis, Pamela; Purkayastha, Das; Gatlin, Marjorie; Vogel, Robert A

    2006-10-01

    Evidence suggests that renin-angiotensin-aldosterone system inhibition ameliorates endothelial dysfunction. The authors examined the effect of amlodipine besylate/benazepril HCl combination treatment compared with amlodipine besylate monotherapy in modulating endothelial dysfunction. This multicenter, double-blind, 12-week study randomized 70 hypertensive subjects with at least one other endothelial dysfunction risk factor to amlodipine besylate/benazepril HCl (5/20 mg/d force-titrated to 5/40 mg/d) or amlodipine besylate monotherapy (5 mg/d force-titrated to 10 mg/d). Both the combination and monotherapy produced significant median increases from baseline in percentage flow-mediated vasodilation (2.0% and 1.2%, respectively) and percentage change in percent flow-mediated vasodilation (25% and 16%, respectively). These improvements were numerically larger with combination treatment, but between-group differences did not achieve statistical significance. Reductions in systolic and diastolic blood pressure were significantly greater (P=.0452/P=.0297) with combination treatment (-18.6/-12.3 mm Hg) than with monotherapy (-14.8/-9.1 mm Hg). A highly positive correlation between change in systolic blood pressure and change in percent of flow-mediated vasodilation was demonstrated only for combination treatment.

  17. Stabilization of Angiotensin-(1-7) by key substitution with a cyclic non-natural amino acid.

    Science.gov (United States)

    Wester, Anita; Devocelle, Marc; Tallant, E Ann; Chappell, Mark C; Gallagher, Patricia E; Paradisi, Francesca

    2017-07-25

    Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide hormone of the renin-angiotensin-aldosterone system, is a promising candidate as a treatment for cancer that reflects its anti-proliferative and anti-angiogenic properties. However, the peptide's therapeutic potential is limited by the short half-life and low bioavailability resulting from rapid enzymatic metabolism by peptidases including angiotensin-converting enzyme (ACE) and dipeptidyl peptidase 3 (DPP 3). We report the facile assembly of three novel Ang-(1-7) analogues by solid-phase peptide synthesis which incorporates the cyclic non-natural δ-amino acid ACCA. The analogues containing the ACCA substitution at the site of ACE cleavage exhibit complete resistance to human ACE, while substitution at the DDP 3 cleavage site provided stability against DPP 3 hydrolysis. Furthermore, the analogues retain the anti-proliferative properties of Ang-(1-7) against the 4T1 and HT-1080 cancer cell lines. These results suggest that ACCA-substituted Ang-(1-7) analogues which show resistance against proteolytic degradation by peptidases known to hydrolyze the native heptapeptide may be novel therapeutics in the treatment of cancer.

  18. The functional c.-2G>C variant of the mineralocorticoid receptor modulates blood pressure, renin, and aldosterone levels.

    Science.gov (United States)

    van Leeuwen, Nienke; Caprio, Massimiliano; Blaya, Carolina; Fumeron, Frédéric; Sartorato, Paola; Ronconi, Vanessa; Giacchetti, Gilberta; Mantero, Franco; Fernandes-Rosa, Fabio L; Simian, Christophe; Peyrard, Sévrine; Zitman, Frans G; Penninx, Brenda W J H; de Kloet, E Ron; Azizi, Michel; Jeunemaitre, Xavier; Derijk, Roel H; Zennaro, Maria-Christina

    2010-11-01

    The mineralocorticoid receptor (MR) is essential in the regulation of volemia and blood pressure. Rare mutations in the MR gene cause type 1 pseudohypoaldosteronism and hypertension. In this study we characterized the common MR polymorphism c.-2G>C (rs2070951) in vitro and tested its influence on parameters related to blood pressure regulation and the renin-angiotensin system. In vitro studies showed that the G allele was associated with decreased MR protein levels and reduced transcriptional activation compared with the C allele. Association studies were performed with several outcome variables in 3 independent cohorts: a mild hypertensive group subjected to a salt-sensitivity test, a healthy normotensive group included in a crossover study to receive both a high and low Na/K diet, and a large cohort (The Netherlands Study of Depression and Anxiety), in which blood pressure was measured. Subjects with the GG genotype had significantly higher plasma renin levels both in the mild hypertensive group and in normal volunteers compared with homozygous C carriers. The GG genotype was also correlated with higher plasma aldosterone levels in healthy subjects. In both the mild hypertensive group and The Netherlands Study of Depression and Anxiety cohort the genotype GG was associated with higher systolic blood pressure in males. In conclusion, the G allele of the common functional genetic polymorphism c.-2G>C in the MR gene associates with increased activation of the renin-angiotensin-aldosterone axis and with increased blood pressure, probably related to decreased MR expression.

  19. Exaggerated natriuresis in adult polycystic kidney disease.

    Science.gov (United States)

    Danielsen, H; Nielsen, A H; Pedersen, E B; Herlevsen, P; Kornerup, H J; Posborg, V

    1986-01-01

    Angiotensin II (AII), aldosterone (Aldo) arginine vasopressin (AVP) in plasma, serum osmolality (Sosm), and renal sodium excretion (UNaV) were studied before and after infusion of hypertonic sodium chloride solution in 20 patients with adult polycystic kidney disease (PKD) with normal or moderately reduced creatinine clearance (Ccr) and in 10 healthy control subjects. UNaV increased after sodium loading in all, significantly more in the PKD patients. AII and Aldo were normal before sodium loading and suppressed after saline in PKD patients and controls. The increase in VNaV correlated with Aldo in patients but not in controls. AVP before loading was increased in hypertensive PKD patients with reduced Ccr, but not in normotensive patients with normal Ccr. After hypertonic saline, Sosm increased to the same degree both in PKD and control subjects, but AVP increased more in those with PKD. The exaggerated natriuresis of PKD is probably not explained by a change in the activity of the renin-angiotensin-aldosterone system. The enhanced response of AVP to osmotic stimuli in PKD may be a compensatory reaction to a reduced renal tubular effect of AVP.

  20. miR-205 mediates the inhibition of cervical cancer cell proliferation using olmesartan.

    Science.gov (United States)

    Yue, Zhang; Yun-Shan, Zhang; Feng-Xia, Xue

    2016-01-01

    The renin-angiotensin-aldosterone system has become known as a prerequisite for tumor angiogenesis that is now recognized as a crucial step in the development of tumors, including cervical cancer. The Ang II-AT1R pathway is known to play an important role in tumor angiogenesis. MicroRNAs (miRNAs) are a class of small, regulating RNAs that participate in tumor genesis, differentiation and proliferation. The current study focused on the anti-tumor mechanism of olmesartan, a novel angiotensin II antagonist, on cervical cancer cells. qRT-PCR and Western blot were used to demonstrate the effect of olmesartan on miR-205 and VEGF-A expression. miR-205 mimics and VEGF-A shRNA plasmid were separately transfected into HeLa and Siha cells to further validate the function of miR-205 and VEGF-A in cervical cancer cell proliferation. It was found that olmesartan could upregulate miR-205 and inhibit VEGF-A expression in HeLa and Siha cells. In addition, VEGF-A was proven to be a target gene of miR-205. This result provides a new idea on the anti-tumor mechanism of olmesartan, which may be used as a novel therapeutic target of cervical cancer.