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Sample records for renin angiotensin aldosterone

  1. Regulation of the renin-angiotensin-aldosterone system in fibromyalgia.

    Science.gov (United States)

    Maliszewski, Anne M; Goldenberg, Don L; Hurwitz, Shelley; Adler, Gail K

    2002-07-01

    To assess the function of the renin-angiotensin-aldosterone (RAA) system in women with fibromyalgia (FM) compared to healthy women. Women with FM [n = 14, age 41.0+/-7.2 yrs, body mass index (BMI) 26.4+/-5.4 kg/m2] and healthy women (n = 13, age 40.0+/-7.7 yrs, BMI 25.0+/-5.0 kg/m2) were placed on a low sodium diet (10 mEq sodium/day) for 5 days. After being supine and fasting overnight, subjects received an intravenous infusion of angiotensin II at successive doses of 1, 3, and 10 ng/kg/min for 45 min per dose. Blood pressure (BP), plasma renin activity (PRA), aldosterone, and cortisol were measured at baseline and after each dose of angiotensin II. Prior to sodium restriction, women with FM completed the Hopkins Symptom Checklist-90, which included a question grading the extent of dizziness/faintness on a scale of 0 (none) to 4 (extremely). After dietary sodium restriction, baseline PRA, aldosterone, and supine BP were similar in healthy women and women with FM. Aldosterone and BP rose in response to infused angiotensin II; these responses did not differ significantly between healthy women and women with FM. In women with FM, symptoms of dizziness correlated inversely with BMI (r = -0.81, p < 0.001) and the systolic BP response to 10 ng/kg/min angiotensin II (r = -0.81, p < 0.001). The functioning of the RAA system, including the vascular response to angiotensin II, was intact in women with FM compared to healthy women. However, women with FM who complained of dizziness had a blunted vascular response to angiotensin II. This blunted vascular response may indicate intravascular volume depletion in women with symptoms of dizziness.

  2. Emerging drugs which target the renin-angiotensin-aldosterone system.

    Science.gov (United States)

    Steckelings, Ulrike Muscha; Paulis, Ludovit; Unger, Thomas; Bader, Michael

    2011-12-01

    The renin-angiotensin-aldosterone system (RAAS) is already the most important target for drugs in the cardiovascular system. However, still new developments are underway to interfere with the system on different levels. The novel strategies to interfere with RAAS aim to reduce the synthesis of the two major RAAS effector hormones, angiotensin (Ang) II and aldosterone, or interfere with their receptors, AT1 and mineralocorticoid receptor, respectively. Moreover, novel targets have been identified in RAAS, such as the (pro)renin receptor, and molecules, which counteract the classical actions of Ang II and are therefore beneficial in cardiovascular diseases. These include the AT2 receptor and the ACE2/Ang-(1-7)/Mas axis. The search for drugs activating these tissue-protective arms of RAAS is therefore the most innovative field in RAAS pharmacology. Most of the novel pharmacological strategies to inhibit the classical RAAS need to prove their superiority above the existing treatment in clinical trials and then have to compete against these now quite cheap drugs in a competitive market. The newly discovered targets have functions beyond the cardiovascular system opening up novel therapeutic areas for drugs interfering with RAAS components.

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

    International Nuclear Information System (INIS)

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

    1983-01-01

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

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

    African Journals Online (AJOL)

    Methods: Patients with diabetes of > 5 years duration, proteinuria at a ... nephropathy, Azotemia, Proteinuria, Aldosterone, Renin, Blood pressure ... Hypertension is a risk factor that exacerbates all ... Arterial tension values of the patients were measured with an. ERKA sleeve .... receiving treatment remained within normal.

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

    Directory of Open Access Journals (Sweden)

    Zhen-Ye Zhang

    2017-09-01

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

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

    International Nuclear Information System (INIS)

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

    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 medicaments for patients with hypertension. The radioimmunoassays can be used for checking the efficiency of medicaments and surgery. (author)

  7. Aldosterone breakthrough with benazepril in furosemide-activated renin-angiotensin-aldosterone system in normal dogs.

    Science.gov (United States)

    Lantis, A C; Ames, M K; Atkins, C E; DeFrancesco, T C; Keene, B W; Werre, S R

    2015-02-01

    Pilot studies in our laboratory revealed that furosemide-induced renin-angiotensin-aldosterone system (RAAS) activation was not attenuated by the subsequent co-administration of benazepril. This study was designed to evaluate the effect of benazepril on angiotensin-converting enzyme (ACE) activity and furosemide-induced circulating RAAS activation. Our hypothesis was that benazepril suppression of ACE activity would not suppress furosemide-induced circulating RAAS activation, indicated by urinary aldosterone concentration. Ten healthy hound dogs were used in this study. The effect of furosemide (2 mg/kg p.o., q12h; Group F; n = 5) and furosemide plus benazepril (1 mg/kg p.o., q24h; Group FB; n = 5) on circulating RAAS was determined by plasma ACE activity, 4-6 h posttreatment, and urinary aldosterone to creatinine ratio (UAldo:C) on days -1, -2, 1, 3, and 7. There was a significant increase in the average UAldo:C (μg/g) after the administration of furosemide (Group F baseline [average of days -1 and -2] UAldo:C = 0.41, SD 0.15; day 1 UAldo:C = 1.1, SD 0.56; day 3 UAldo:C = 0.85, SD 0.50; day 7 UAldo:C = 1.1, SD 0.80, P Benazepril suppressed ACE activity (U/L) in Group FB (Group FB baseline ACE = 16.4, SD 4.2; day 1 ACE = 3.5, SD 1.4; day 3 ACE = 1.6, SD 1.3; day 7 ACE = 1.4, SD 1.4, P Benazepril decreased plasma ACE activity but did not prevent furosemide-induced RAAS activation, indicating aldosterone breakthrough (escape). This is particularly noteworthy in that breakthrough is observed at the time of initiation of RAAS suppression, as opposed to developing after months of therapy. © 2014 John Wiley & Sons Ltd.

  8. 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

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

    DEFF Research Database (Denmark)

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

    2018-01-01

    The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt...... that seems to decouple the activity of the renin-angiotensin-aldosterone system from changes in renal hemodynamics. This may serve as a negative feed-back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect...... of rhEPO on renal hemodynamics and a decoupling of the renin-angiotensin-aldosterone system....

  10. 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.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  12. The renin-angiotensin-aldosterone system and calcium-regulatory hormones.

    Science.gov (United States)

    Vaidya, A; Brown, J M; Williams, J S

    2015-09-01

    There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium-regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis, while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control. Hyperaldosteronism and hyperparathyroidism represent pathophysiologic conditions that may contribute to or perpetuate each other; aldosterone regulates parathyroid hormone and associates with adverse skeletal complications, and parathyroid hormone regulates aldosterone and associates with adverse cardiovascular complications. As dysregulation in both systems is linked to poor cardiovascular and skeletal health, it is increasingly important to fully characterize how they interact to more precisely understand their impact on human health and potential therapies to modulate these interactions. This review describes the known clinical interactions between these two systems including observational and interventional studies. Specifically, we review studies describing the inhibition of renin activity by calcium and vitamin D, and a potentially bidirectional and stimulatory relationship between aldosterone and parathyroid hormone. Deciphering these relationships might clarify variability in outcomes research, inform the design of future intervention studies and provide insight into the results of prior and ongoing intervention studies. However, before these opportunities can be addressed, more effort must be placed on shifting observational data to the proof of concept phase. This will require reallocation of resources to conduct interventional studies and secure the necessary talent.

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

    Aachmann-Andersen, Niels J; Christensen, Soren J; Lisbjerg, Kristian; Oturai, Peter; Johansson, Pär I; Holstein-Rathlou, Niels-Henrik; Olsen, Niels V

    2018-03-01

    The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance). rhEPO increased arterial blood pressure, total peripheral resistance, and renal vascular resistance, and decreased renal plasma flow in the high-dose rhEPO intervention and tended to decrease GFR. In spite of the decrease in renal perfusion, rhEPO tended to decrease reabsorption of sodium and water in the proximal tubule and induced a prompt decrease in circulating levels of renin and aldosterone, independent of changes in red blood cell mass, blood volumes, and blood pressure. We also found changes in biomarkers showing evidence that rhEPO induced a prothrombotic state. Our results suggest that rhEPO causes a direct downregulation in proximal tubular reabsorption that seems to decouple the activity of the renin-angiotensin-aldosterone system from changes in renal hemodynamics. This may serve as a negative feed-back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect of rhEPO on renal hemodynamics and a decoupling of the renin-angiotensin-aldosterone system. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  15. Expressions of renin, angiotensin II and aldosterone in patients with viral hepatitis or hepatic cirrhosis

    International Nuclear Information System (INIS)

    Huo Ying; Zhu Yalin; Liu Yun

    2008-01-01

    Objective: To explore the changes of renin, angiotensin and aldosterone system in patients with hepatic disorders. Methods: Plasma renin activity (PRA), AT-II and Ald levels were measured with RIA in 31 patients with viral hepatitis, 35 patients with hepatic cirrhosis and 38 controls. Results: The levels of PRA, AT-II and Ald in patients with viral hepatitis were slightly but non-significantly higher than those in controls (P>0.05). The levels of PRA, AT-II and Ald in patients with cirrhosis were significantly higher than those in controls (P<0.01). Conclusion: RAAS was activated during progression of hepatic disorders and participated in the development of hepatic fibrosis. (authors)

  16. [The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome].

    Science.gov (United States)

    Cui, Jia; Dou, Jingtao; Yang, Guoqing; Zang, Li; Jin, Nan; Chen, Kang; Du, Jin; Gu, Weijun; Wang, Xianling; Yang, Lijuan; Lyu, Zhaohui; Ba, Jianming; Mu, Yiming; Lu, Juming; Li, Jiangyuan; Pan, Changyu

    2015-07-01

    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. 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. 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, PCushing'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 (PCushing's syndrome was similar to that in normal control. The basal PAC level and its response to upright posture are differently associated with ACTH level in Cushing's syndrome.

  17. Analysis of renin-angiotensin aldosterone system gene polymorphisms in malaysian essential hypertensive and type 2 diabetic subjects

    OpenAIRE

    Ramachandran, Vasudevan; Ismail, Patimah; Stanslas, Johnson; Shamsudin, Norashikin

    2009-01-01

    Abstract Background The renin-angiotensin aldosterone system (RAAS) plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT), MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin) of RAAS...

  18. [Differences of blood plasma renin activity, angiotensin II and aldosterone levels in essential or secondary hypertension].

    Science.gov (United States)

    Song, Ai-ling; Zeng, Zheng-pei; Tong, An-li; Lu, Lin; Chen, Shi; Li, Ming; Fu, Chun-li; Wang, Yong-hui; Sun, Mei-li

    2012-04-01

    To study on the difference of plasma renin activity (PRA), angiotensin II (Ang II), and aldosterone levels in patients with essential hypertension (EH) or primary aldosteronism (PA) or pheochromocytoma (PHEO), and to analyze the sensitivity and specificity on the diagnosis of PA among patients with hypertension with aldosterone/PRA ratio (ARR). The plasma aldosterone, Ang II and PRA concentrations in supine and upright positions were measured by radioimmunoassay from 413 patients including idiopathic hyperaldosteronism (IHA, n = 111), aldosterone-producing adenoma (APA, n = 118), PHEO (n = 98) and EH (n = 86). ARR was calculated. Plasma aldosterone concentrations in both of supine and upright positions in PHEO group [374 (294, 465) pmol/L and 629 (449, 997) pmol/L] and PA group [471 (346, 632) pmol/L and 673 (499, 825) pmol/L] were higher than those in EH group [277 (224, 332) pmol/L and 427 (341, 501) pmol/L] (P 0.05). The PRA level in both positions of each group were PHEO group [0.3 (0.2, 1.0) µg · L(-1) · h(-1) and 1.4 (0.6, 3.4) µg · L(-1) · h(-1)] > EH group [0.2 (0.1, 0.4) µg · L(-1) · h(-1) and 0.6 (0.4, 1.0) µg · L(-1) · h(-1)] (P PA group [0.1 (0.1, 0.1) µg · L(-1) · h(-1) and 0.2 (0.1, 0.3) µg · L(-1) · h(-1)] (P < 0.01), and APA group [0.1 (0.1, 0.1) µg · L(-1) · h(-1) and 0.1 (0.1, 0.3) µg · L(-1) · h(-1)] < IHA group [0.1 (0.1, 0.2) µg · L(-1) · h(-1) and 0.2 (0.1, 0.3) µg · L(-1) · h(-1)] (supine P < 0.01; upright P < 0.05). APA was divided into 2 types with renin-Ang II-responsive APA (n = 26) and unresponsive APA (n = 92). The plasma aldosterone concentration was lower in supine position but higher in upright position in renin-Ang II-responsive APA than in unresponsive APA patients. ARR in upright was higher in PA group (P < 0.01) but lower in PHEO group (P < 0.05) compared with EH. ARR was higher in APA than in IHA (P < 0.01). The sensitivity and specificity of ARR as 40 (aldosterone unit: ng/dl; PRA unit: µg · L(-1

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

    Directory of Open Access Journals (Sweden)

    Monika Chaszczewska-Markowska

    2016-09-01

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

  20. [Renin-angiotensin-aldosterone system activity during head-up tilt testing in patients with vasovagal syncope].

    Science.gov (United States)

    Gajek, Jacek; Zyśko, Dorota; Mazurek, Walentyna

    2005-08-01

    The stimulation of renin-angiotensin-aldosterone (RAA) system during tilt table test is caused by sympathetic nervous system activation by orthostatic stress and a serotonin release as well. In healthy individuals increase of plasma renin activity during test with maximal values on the peak of the test was described. The aim of the study was to assess the activation of RAAS in patients with neurally mediated syncope during the tilt table test by means of plasma renin activity and serum aldosterone levels. The study was carried out in 31 patients aged 39.4 +/- 15.0 years (18 women and 13 men) with neurally mediated syncope during tilt test. Plasma renin activity was assessed in the baseline conditions, immediately after the test and 10 minutes after the test using radioenzymatic assay. Aldosterone concentrations were measured radioimmunologically, twice: after 30 minutes supine rest and after the syncope. Plasma renin activity during supine rest was 2.2 +/- 2.4 ng/ml/h, rose after the syncope 2.5-fold to 5.2 +/- 4.5 ng/ml/h (p < 0.001 comparing to baseline) stayed on similar level approximately for the next 10 minutes--4.9 +/- 5.5 ng/ml/h (p = n.s.). In 11 patients (35%) 10 minutes after the test even further increase of PRA was observed. Serum aldosterone level increased significantly immediately after tilt test (90.0 +/- 72.9 vs 178.8 +/- 150.1 pg/ml, p < 0.01). Authors showed, that in patients with NMS plasma renin activity increases and this increase lasts for 10 minutes after the syncope and the concentration of aldosterone increases immediately after tilt test.

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

    Science.gov (United States)

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

    2015-06-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  3. MODULATION OF THE CARDIAC SODIUM/BICARBONATE COTRANSPORTER BY THE RENIN ANGIOTENSIN ALDOSTERONE SYSTEM: PATHOPHYSIOLOGICAL CONSEQUENCES.

    Directory of Open Access Journals (Sweden)

    Verónica Celeste De Giusti

    2014-01-01

    Full Text Available The sodium/bicarbonate cotransporter (NBC is one of the major alkalinizing mechanisms in the cardiomyocytes. It has been demonstrated the existence of at least two functional isoforms, one that promotes the co-influx of 1 molecule of Na+ per 1 molecule of HCO3- (electroneutral isoform; NBCn1 and the other one that generates the co-influx of 1 molecule of Na+ per 2 molecules of HCO3- (electrogenic isoform; NBCe1. Both isoforms are important to maintain intracellular pH (pHi and sodium concentration ([Na+]i. In addition, NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD. The renin-angiotensin-aldosterone system (RAAS is implicated in the modulation of almost all physiological cardiac functions and is also involved in the development and progression of cardiac diseases. It was reported that angiotensin II (Ang II exhibits an opposite effect on NBC isoforms: it activates NBCn1 and inhibits NBCe1. The activation of NBCn1 leads to an increase in pHi and [Na+]i, which indirectly, due to the stimulation of reverse mode of the Na+/Ca2+ exchanger (NCX, conduces to an increase in the intracellular Ca2+ concentration. On the other hand, the inhibition of NBCe1 generates an APD prolongation, potentially representing a risk of arrhythmias. In the last years, the potentially altered NBC function in pathological scenarios, as cardiac hypertrophy and ischemia-reperfusion, has raised increasing interest among investigators. This review attempts to draw the attention on the relevant regulation of NBC activity by RAAS, since it modulates pHi and [Na+]i, which are involved in the development of cardiac hypertrophy, the damage produced by ischemia-reperfusion and the generation of arrhythmic events, suggesting a potential role of NBC in cardiac diseases.

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

    Science.gov (United States)

    Rebrov, B A

    1996-01-01

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

  5. Living alone and activation of the renin-angiotensin-aldosterone-system: Differential effects depending on alexithymic personality features.

    Science.gov (United States)

    Terock, Jan; Hannemann, Anke; Janowitz, Deborah; Völzke, Henry; Nauck, Matthias; Freyberger, Harald-Jürgen; Wallaschofski, Henri; Grabe, Hans Jörgen

    2017-05-01

    Living alone is considered as a chronic stress factor predicting different health conditions and particularly cardiovascular disease (CVD). Alexithymia is associated with increased psychological distress, less social skills and fewer close relationships, making alexithymic subjects particularly susceptible to chronic stress imposed by "living alone". Only few studies investigated the renin-angiotensin-aldosterone-system (RAAS) activity in response to chronic stress. We aimed at evaluating the effects of "living alone" as a paradigm for chronic stress on RAAS activity and putatively differential effects depending on alexithymic personality features. Alexithymia and serum concentrations of renin and aldosterone were measured in 944 subjects from the population-based SHIP-1 study. Subgroups were formed using the median of the Toronto Alexithymia Scale-20 (TAS-20) and a cohabitation status of "living alone" or "living together". Analyses were adjusted for various psychosocial, behavioral and metabolic risk factors. "Living alone" was associated with elevated plasma renin (p<0.01, β=0.138) but not aldosterone concentrations in the total sample. On subgroup level, we found associations of "living alone" and elevated renin concentrations only in subjects low in TAS-20 scores (p<0.01, β=0.219). Interactional effects of alexithymia×cohabitation status were found for the aldosterone-to-renin ratio (p=0.02, β=-0.234). The association of chronic stress imposed by "living alone" with increased RAAS activity contributes to explain the relationship of this psychosocial stress condition and increased risk for CVD. In contrast, alexithymic subjects may be less affected by the deleterious effects of "living alone". Copyright © 2017 Elsevier Inc. All rights reserved.

  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 H

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

  7. Pharmacokinetic/Pharmacodynamic Modeling of Renin-Angiotensin Aldosterone Biomarkers Following Angiotensin-Converting Enzyme (ACE) Inhibition Therapy with Benazepril in Dogs.

    Science.gov (United States)

    Mochel, Jonathan P; Fink, Martin; Peyrou, Mathieu; Soubret, Antoine; Giraudel, Jérôme M; Danhof, Meindert

    2015-06-01

    The objective of this research was to provide a comprehensive description of the effect of benazepril on the dynamics of the renin-angiotensin aldosterone system (RAAS) in dogs. Blood specimens for renin activity (RA), angiotensin II (AII), and aldosterone (ALD) quantitation in plasma were drawn from 12 healthy adult beagle dogs randomly allocated to 2 treatment groups: (i) benazepril 5 mg PO, q24 h (n: 6) and (ii) placebo (n: 6), in a cross-over design. A mechanism-based pharmacokinetic/pharmacodynamic model, which includes the periodic nature of RA, AII, and ALD during placebo treatment and the subsequent changes in dynamics following repeated dosing with benazepril, was developed. The disposition kinetics of benazepril active metabolite, benazeprilat, was characterized using a saturable binding model to the angiotensin converting enzyme. The modulatory effect of benazeprilat on the RAAS was described using a combination of immediate response models. Our data show that benazepril noticeably influences the dynamics of the renin cascade, resulting in a substantial decrease in AII and ALD, while increasing RA throughout the observation span. The model provides a quantitative framework for better understanding the effect of ACE inhibition on the dynamics of the systemic RAAS in dogs.

  8. 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 place...... 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.......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...

  9. 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...

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  11. 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.

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

    NARCIS (Netherlands)

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

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

  13. Analysis of renin-angiotensin aldosterone system gene polymorphisms in malaysian essential hypertensive and type 2 diabetic subjects

    Directory of Open Access Journals (Sweden)

    Stanslas Johnson

    2009-02-01

    Full Text Available Abstract Background The renin-angiotensin aldosterone system (RAAS plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT, MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin of RAAS genes in Malaysian essential hypertensive and type 2 diabetic subjects. Methods RAAS gene polymorphisms were determined using mutagenically separated PCR and PCR-RFLP method in a total of 270 subjects consisting of 70 hypertensive subjects without type 2 diabetes mellitus (T2DM, 60 T2DM, 65 hypertensive subjects with T2DM and 75 control subjects. Results There was significant difference found in age, body mass index, systolic/diastolic blood pressure, fasting plasma glucose and high density lipoprotein cholesterol levels between the hypertensive subjects with or without T2DM and control subjects. No statistically significant differences between groups were found in the allele frequency and genotype distribution for A20C variant of AGT gene, MboI of renin, Gly460Trp of aldosterone and Lys173Arg of adducin (p > 0.05. However, the results for A6G of AGT gene revealed significant differences in allele and genotype frequencies in essential hypertension with or without T2DM (p Conclusion Among the five polymorphisms of RAAS genes only A6G variant of AGT gene was significantly associated in Malaysian essential hypertensive and type 2 diabetic subjects. Therefore, A6G polymorphism of the AGT gene could be a potential genetic marker for increased susceptibility to essential hypertension with or without T2DMin Malaysian subjects.

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

    International Nuclear Information System (INIS)

    Eliahou, H.E.; Iaina, A.

    1980-01-01

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

  15. 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.

  16. The influence of a tilt training programme on the renin-angiotensin-aldosterone system activity in patients with vasovagal syncope.

    Science.gov (United States)

    Gajek, Jacek; Zyśko, Dorota; Krzemińska, Sylwia; Mazurek, Walentyna

    2009-08-01

    We assessed the influence of short-term and long-term tilt training on the activity of the renin-angiotensin-aldosterone system (RAAS) in vasovagal patients. Thirty-nine patients (28 F, 11 M) aged 39.7 +/- 11.2 years with a history of vasovagal syncope and a positive head-up tilt test (HUT) were studied. Blood samples for plasma renin activity (PRA) and aldosterone (ALDO) concentration were drawn at the baseline, immediately after HUT and 10 min after HUT, during the diagnostic, the negative short-term (2-5 days) follow-up HUT and long-term (1-3 months) follow-up HUT. Tilt training was started after diagnostic HUT. In diagnostic HUT, PRA increased significantly immediately after HUT comparing to the baseline, during recovery the values did not change. ALDO concentration increased after HUT comparing to baseline and further increased during recovery. After short-term tilt training, PRA and ALDO concentrations did not significantly change compared to their corresponding values in diagnostic HUT. After long-term tilt training, PRA did not significantly change compared to the values in the diagnostic and short-term follow-up HUT. ALDO concentration also did not change significantly at the baseline and immediately after HUT, and 10 min after HUT ALDO concentration was significantly lower than after diagnostic HUT. Tilt training changes the response of RAAS to the prolonged orthostasis in vasovagal patients. The coupling between PRA and ALDO after diagnostic HUT has been found to be altered and the physiological relationship was restored after long-term tilt training. The beneficial effect of tilt training depends partially on changed RAAS activation.

  17. 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

    , 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....

  18. 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.

  19. Renoprotection by blockade of the renin-angiotensin-aldosterone system in diabetic and non-diabetic chronic kidney disease. Specific involvement of intra-renal angiotensin-converting enzyme activity in therapy resistance?

    NARCIS (Netherlands)

    Vogt, L.; Kocks, M. J. A.; Laverman, G. D.; Navis, G.

    2004-01-01

    Data of numerous clinical trials show that lowering of blood pressure is prerequisite for reducing the rate of renal function loss in chronic renal disease. There is evidence supporting that blood pressure lowering obtained by intervention in the renin-angiotensin-aldosterone system (RAAS) has an

  20. Capturing the dynamics of systemic Renin-Angiotensin-Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs.

    Science.gov (United States)

    Mochel, J P; Peyrou, M; Fink, M; Strehlau, G; Mohamed, R; Giraudel, J M; Ploeger, B; Danhof, M

    2013-04-01

    In dogs, activation of the Renin-Angiotensin-Aldosterone System (RAAS) is an important feature of congestive heart failure (CHF). Long-term increases in angiotensin II (AII) and aldosterone (ALD) lead to the progression of heart failure to its end stage. Angiotensin-converting enzyme inhibitors (ACEIs) are the foremost therapeutic option in the management of CHF. Recent literature has challenged the efficacy of ACEIs, based on modest reduction in urinary aldosterone (UALD) excretion despite marked inhibition of ACE activity. This study was designed to heighten the understanding of the effect of benazepril, a potent ACEI, on the RAAS, using a low-sodium diet as an experimental model of RAAS activation. Time course profiles of RAAS peptides and related areas under the curve (AUC) were used for comparison between benazepril and placebo groups. Results indicated substantial changes in the dynamics of these biomarkers. At presumed benazeprilat steady state, significant differences in AUC of plasma renin activity (+90%), angiotensin I (+43%), and AII (-53%) were found between benazepril and placebo-treated dogs. ALD decreased by 73% in plasma but only by 5% in urine. In conclusion, despite modest reduction in UALD excretion, benazepril markedly influences RAAS dynamics in dogs. © 2012 Blackwell Publishing Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Effect of all-trans retinoic acid treatment on prohibitin and renin-angiotensin-aldosterone system expression in hypoxia-induced renal tubular epithelial cell injury.

    Science.gov (United States)

    Zhou, Tian-Biao; Ou, Chao; Rong, Liang; Drummen, Gregor P C

    2014-09-01

    All-trans retinoic acid (ATRA) exerts various effects on physiological processes such as cell growth, differentiation, apoptosis and inflammation. Prohibitins (PHB), including prohibitin 1 (PHB1) and prohibitin 2 (PHB2), are evolutionary conserved and pleiotropic proteins implicated in various cellular functions, including proliferation, tumor suppression, apoptosis, transcription, and mitochondrial protein folding. The renin-angiotensin-aldosterone system plays a pivotal role in the regulation of blood pressure and volume homeostasis. All these factors and systems have been implicated in renal interstitial fibrosis. Therefore, the objective of this study was to investigate the effect of ATRA treatment on the renin-angiotensin-aldosterone system and expression of prohibitins to further understand its role in the processes leading to renal interstitial fibrosis. The hypoxic and oxidative stress conditions in obstructive renal disease were simulated in a hypoxia/reoxygenation model with renal tubular epithelial cells (RTEC) as a model system. Subsequently, the effect of ATRA on mRNA and protein expression levels was determined and correlations were established between factors involved in the renin-angiotensin-aldosterone system, the prohibitins, cellular redox status, renal interstitial fibrosis and ATRA treatment. Correlation analysis showed that both PHB1 and PHB2 protein levels were negatively correlated with angiotensin I, ACE1, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA (PHB1: r = -0.792, -0.834, -0.805, -0.795, -0.778, -0.798, -0.751, -0.682; PHB2: r = -0.872, -0.799, -0.838, -0.773, -0.769, -0.841, -0.794, -0.826; each p system under hypoxia/reoxygenation conditions. © The Author(s) 2014.

  3. Investigating the association of vitamin D with blood pressure and the renin-angiotensin-aldosterone system in hypertensive subjects: a cross-sectional prospective study.

    Science.gov (United States)

    Cremer, Antoine; Tambosco, Chloé; Corcuff, Jean-Benoît; Boulestreau, Romain; Gaillard, Prune; Lainé, Marion; Papaioannou, Georgios; Gosse, Philippe

    2018-02-01

    The hypothesis that vitamin D (25(OH)D) insufficiency plays a role in occurring of various disease has led to a rise in requests of dosages and to an increase of health-care costs. 25(OH)D insufficiency is associated with increased risk of cardiovascular disease and hypertension in many studies. Animal studies demonstrated that 25(OH)D insufficiency activates renin angiotensin system but corresponding humans data are limited. The aim of the study was to document relationship between 25(OH)D, blood pressure, and renin angiotensin system in hypertensive subjects. In all, 248 hypertensive individuals, 46.8 years (±14), were hospitalized for an etiological assessment of hypertension in this cross-sectional study over two calendar years. 25(OH)D, plasma renin activity, and aldosterone were determined in stringent conditions and blood pressure was measure. Statistical analyses were carried out to analyze the association between 25(OH)D, blood pressure, and renin angiotensin system using linear and logistic regressions with adjustments on relevant variables. In all, 80% of the studied population had a 25(OH)D insufficiency. There were no significant association between 25(OH)D and levels of systolic or diastolic blood pressure, plasma renin activity, and aldosterone whatever the statiscal method used after adjustment. 25(OH)D is not associated with blood pressure and renin angiontensin component in hypertensive subjects. These results corroborate the interventional studies which are for a large majority negatives. A new definition of the 25(OH)D insufficiency in general population is necessary.

  4. Renin-angiotensin-aldosterone system inhibitors improve membrane stability and change gene-expression profiles in dystrophic skeletal muscles.

    Science.gov (United States)

    Chadwick, Jessica A; Bhattacharya, Sayak; Lowe, Jeovanna; Weisleder, Noah; Rafael-Fortney, Jill A

    2017-02-01

    Angiotensin-converting enzyme inhibitors (ACEi) and mineralocorticoid receptor (MR) antagonists are FDA-approved drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) and are used to treat heart failure. Combined treatment with the ACEi lisinopril and the nonspecific MR antagonist spironolactone surprisingly improves skeletal muscle, in addition to heart function and pathology in a Duchenne muscular dystrophy (DMD) mouse model. We recently demonstrated that MR is present in all limb and respiratory muscles and functions as a steroid hormone receptor in differentiated normal human skeletal muscle fibers. The goals of the current study were to begin to define cellular and molecular mechanisms mediating the skeletal muscle efficacy of RAAS inhibitor treatment. We also compared molecular changes resulting from RAAS inhibition with those resulting from the current DMD standard-of-care glucocorticoid treatment. Direct assessment of muscle membrane integrity demonstrated improvement in dystrophic mice treated with lisinopril and spironolactone compared with untreated mice. Short-term treatments of dystrophic mice with specific and nonspecific MR antagonists combined with lisinopril led to overlapping gene-expression profiles with beneficial regulation of metabolic processes and decreased inflammatory gene expression. Glucocorticoids increased apoptotic, proteolytic, and chemokine gene expression that was not changed by RAAS inhibitors in dystrophic mice. Microarray data identified potential genes that may underlie RAAS inhibitor treatment efficacy and the side effects of glucocorticoids. Direct effects of RAAS inhibitors on membrane integrity also contribute to improved pathology of dystrophic muscles. Together, these data will inform clinical development of MR antagonists for treating skeletal muscles in DMD. Copyright © 2017 the American Physiological Society.

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

    Science.gov (United States)

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

    2015-01-01

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

  6. 8C.03: A KEY ROLE FOR ENDOTHELIN-1 IN THE PATHOGENESIS OF PREECLAMPSIA AND THE ASSOCIATED SUPPRESSION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM.

    Science.gov (United States)

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

    2015-06-01

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

  7. Renin-angiotensin II-aldosterone system blockers and time to renal replacement therapy in children with CKD.

    Science.gov (United States)

    Abraham, Alison G; Betoko, Aisha; Fadrowski, Jeffrey J; Pierce, Christopher; Furth, Susan L; Warady, Bradley A; Muñoz, Alvaro

    2017-04-01

    Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin-angiotensin II-aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD. A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m 2 , median urine protein to creatinine ratio: 0.35 mg/mg) were included. RAAS use was reported at annual study visits. Both Cox proportional hazards models with time-varying RAAS exposure and Cox marginal structural models (MSM) were used to evaluate the effect of RAAS use on time to RRT. Analyses were adjusted or weighted to control for age, male sex, glomerular diagnosis, GFR, nephrotic range proteinuria, anemia, elevated blood pressure, acidosis, elevated phosphate and elevated potassium. There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 %) were prevalent RAAS users, who were more likely to be older, have a glomerular etiology, have higher urine protein, be anemic, have elevated serum phosphate and potassium, take more medications, but less likely to have elevated blood pressure, compared with non-users. RAAS use was found to reduce the risk of RRT by 21 % (hazard ratio: 0.79) to 37 % (hazard ratio: 0.63) from standard regression adjustment and MSM models, respectively. These results support inferences from adult studies of a substantial benefit of RAAS use in pediatric CKD patients.

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Science.gov (United States)

    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.

  10. Effects of high doses of enalapril and benazepril on the pharmacologically activated renin-angiotensin-aldosterone system in clinically normal dogs.

    Science.gov (United States)

    Ames, Marisa K; Atkins, Clarke E; Lee, Seunggon; Lantis, Andrea C; zumBrunnen, James R

    2015-12-01

    To determine whether high doses of enalapril and benazepril would be more effective than standard doses of these drugs in suppressing the furosemide-activated renin-angiotensin-aldosterone system (RAAS). 6 healthy Beagles. 2 experiments were conducted; each lasted 10 days, separated by a 2-week washout period. In experiment 1, all dogs received furosemide (2 mg/kg, PO, q 12 h) and enalapril (1 mg/kg, PO, q 12 h) for 8 days (days 0 through 7). In experiment 2, dogs received furosemide (2 mg/kg, PO, q 12 h) and benazepril (1 mg/kg, PO, q 12 h) for 8 days. Effects on the RAAS were determined by assessing serum angiotensin-converting enzyme (ACE) activity on days -1, 3, and 7; serum aldosterone concentration on days -2, -1, 1, 3, and 7; and the urinary aldosterone-creatinine ratio (UAldo:C) in urine collected in the morning and evening of days -2, -1, 1, 3, and 7. High doses of enalapril and benazepril caused significant reductions in serum ACE activity on all days but were not more effective than standard doses used in other studies. Mean UAldo:C remained significantly higher on days 2 through 7, compared with baseline values. Serum aldosterone concentration also increased after drug administration, which mirrored changes in the UAldo:C. In this study, administration of high doses of enalapril and benazepril significantly inhibited ACE activity, yet did not prevent increases in mean urine and serum aldosterone concentrations resulting from furosemide activation of RAAS. This suggested that aldosterone breakthrough from ACE inhibition was a dose-independent effect of ACE inhibitors.

  11. Maternal corticosterone exposure in the mouse programs sex-specific renal adaptations in the renin-angiotensin-aldosterone system in 6-month offspring.

    Science.gov (United States)

    Cuffe, James S M; Burgess, Danielle J; O'Sullivan, Lee; Singh, Reetu R; Moritz, Karen M

    2016-04-01

    Short-term maternal corticosterone (Cort) administration at mid-gestation in the mouse reduces nephron number in both sexes while programming renal and cardiovascular dysfunction in 12-month male but not female offspring. The renal renin-angiotensin-aldosterone system (RAAS), functions in a sexually dimorphic manner to regulate both renal and cardiovascular physiology. This study aimed to identify if there are sex-specific differences in basal levels of the intrarenal RAAS and to determine the impact of maternal Cort exposure on the RAAS in male and female offspring at 6 months of age. While intrarenal renin concentrations were higher in untreated females compared to untreated males, renal angiotensin II concentrations were higher in males than females. Furthermore, basal plasma aldosterone concentrations were greater in females than males. Cort exposed male but not female offspring had reduced water intake and urine excretion. Cort exposure increased renal renin concentrations and elevated mRNA expression of Ren1, Ace2, and Mas1 in male but not female offspring. In addition, male Cort exposed offspring had increased expression of the aldosterone receptor, Nr3c2 and renal sodium transporters. In contrast, Cort exposure increased Agtr1a mRNA levels in female offspring only. This study demonstrates that maternal Cort exposure alters key regulators of renal function in a sex-specific manner at 6 months of life. These finding likely contribute to the disease outcomes in male but not female offspring in later life and highlights the importance of renal factors other than nephron number in the programming of renal and cardiovascular disease. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  12. Effect of maternal renin-angiotensin-aldosterone system activation on social coping strategies and gene expression of oxytocin and vasopressin in the brain of rat offspring in adulthood.

    Science.gov (United States)

    Senko, Tomáš; Svitok, Pavel; Kršková, Lucia

    2017-10-01

    The intrauterine condition in which the mammalian foetus develops has an important role in prenatal programming. The aim of this study was to determine the extent to which activation of the maternal renin-angiotensin-aldosterone system (RAAS) could influence social behaviour strategies in offspring via changes in social neurotransmitters in the brain. Pregnant female Wistar rats were implanted with osmotic minipumps which continually released angiotensin II for 14 days at concentration of 2 μg/kg/h. The adult offspring (angiotensin and control groups) underwent a social interaction test. The mRNA expression of vasopressin, oxytocin and the oxytocin receptor in selected brain areas was measured by in situ hybridisation. Prenatal exposure to higher levels of angiotensin II resulted in a strong trend toward decreased total social interaction time and significantly decreased time spent in close proximity and frequency of mutual sniffing. The angiotensin group showed no changes in oxytocin mRNA expression in the hypothalamic paraventricular or supraoptic nuclei, but this group had reduced vasopressin mRNA expression in the same areas. We concluded that maternal activation of RAAS (via higher levels of angiotensin II) caused inhibition of some socio-cohesive indicators and decreased vasopressinergic activity of offspring. Taken together, these results suggest a reactive rather than proactive social coping strategy.

  13. Nephroprotective action of renin-angiotensin-aldosterone system blockade in chronic kidney disease patients: the landscape after ALTITUDE and VA NEPHRON-D trails.

    Science.gov (United States)

    Rutkowski, Boleslaw; Tylicki, Leszek

    2015-03-01

    The intervention in the renin-angiotensin-aldosterone system (RAAS) is currently the most effective strategy that combines blood pressure lowering and renoprotection. Several large, randomized, controlled trials evidenced the renoprotective potential of the angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in nephropathies of almost any etiology. Mineralocorticoid receptor antagonists and direct renin inhibitor, aliskiren, as add-on treatments to standard therapy including the optimal dose of ACEIs or ARBs reduce albuminuria or proteinuria and slow development of renal dysfunction more than placebo. No clinical evidence is available however about whether these strategies may influence on long-term kidney outcome. Three recent trials suggested that aggressive RAAS blockade, that is, combination of 2 RAAS-blocking agents, does not decrease cardiovascular and renal morbidity and may carry an increased risk of serious complications. This article reviews an evidence-based approach on the use of RAAS-inhibiting agents in chronic kidney disease and considers the implementation of dual RAAS blockade with reference to the results of ALTITUDE and VA NEPHRON-D trails aiming to aid clinicians in their treatment decisions for patients with chronic kidney disease. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  14. The renin–angiotensin–aldosterone system blockade in patients with advanced diabetic kidney disease

    Directory of Open Access Journals (Sweden)

    Sheila Bermejo

    2018-03-01

    Full Text Available Background and objectives: Diabetic kidney disease is the leading cause of end-stage chronic kidney disease (CKD. The renin–angiotensin–aldosterone system (RAAS blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up. Materials and methods: Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade, patients who at some point had received RAAS blockade (inconstant-RAAS blockade and patients who received RAAS blockade (constant-RAAS blockade. Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated hemoglobin and glomerular filtration rate according to CKD-EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up in terms of treatment group, survival, risk factors and renal prognosis. Results: Non-RAAS blockade patients had worse renal function and older age (p < 0.05 at baseline compared to RAAS blockade patients. Patients who received RAAS blockade were not found to have greater toxicity or chronic kidney disease progression and no differences in renal prognosis were identified. Mortality was higher in non-RAAS blockade patients, older patients and patients with worse renal function (p < 0.05. In the multivariate analysis, older age and worse renal function were risk factors for mortality. Conclusions: Treatment with RAAS blockade is more common in diabetic kidney disease patients with eGFR ≥ 30 ml/min/1.73 m2. In our study, there were no differences in the evolution of renal function

  15. Aldosterone and Renin Test

    Science.gov (United States)

    ... 1989. Laurence M. Demers, PhD. Distinguished Professor of Pathology and Medicine, The Pennsylvania State University College of ... 74-79, 946-951. Holt, E. (Updated 2008 March 18). Aldosterone. MedlinePlus Medical Encyclopedia On-line information]. ...

  16. 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

    Directory of Open Access Journals (Sweden)

    Yuki Narita

    2016-02-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2016-05-25

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

  18. The role of renin-angiotensin-aldosterone system genes in the progression of chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.

    Science.gov (United States)

    Kelly, Tanika N; Raj, Dominic; Rahman, Mahboob; Kretzler, Matthias; Kallem, Radhakrishna R; Ricardo, Ana C; Rosas, Sylvia E; Tao, Kaixiang; Xie, Dawei; Hamm, Lotuce Lee; He, Jiang

    2015-10-01

    We conducted single-marker, gene- and pathway-based analyses to examine the association between renin-angiotensin-aldosterone system (RAAS) variants and chronic kidney disease (CKD) progression among Chronic Renal Insufficiency Cohort study participants. A total of 1523 white and 1490 black subjects were genotyped for 490 single nucleotide polymorphisms (SNPs) in 12 RAAS genes as part of the ITMAT-Broad-CARe array. CKD progression phenotypes included decline in estimated glomerular filtration rate (eGFR) over time and the occurrence of a renal disease event, defined as incident end-stage renal disease or halving of eGFR from baseline. Mixed-effects models were used to examine SNP associations with eGFR decline, while Cox proportional hazards models tested SNP associations with renal events. Gene- and pathway-based analyses were conducted using the truncated product method. All analyses were stratified by race, and a Bonferroni correction was applied to adjust for multiple testing. Among white and black participants, eGFR declined an average of 1.2 and 2.3 mL/min/1.73 m(2)/year, respectively, while renal events occurred in a respective 11.5 and 24.9% of participants. We identified strong gene- and pathway-based associations with CKD progression. The AGT and RENBP genes were consistently associated with risk of renal events in separate analyses of white and black participants (both P renal events in both groups (both P < 1.00 × 10(-6)). No single-marker associations with CKD progression were observed. The current study provides strong evidence for a role of the RAAS in CKD progression. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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

    Science.gov (United States)

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

    2016-06-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    to angiotensin receptor blockers; n=5) or NSAIDs (n=1), changing from RAASi to NSAIDs (n=2), and changing from high to low sodium intake (n=5). A two-stage meta-analysis was conducted: Deming regression was conducted in each study to assess correlations in response, and individual study results were then meta...

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

    International Nuclear Information System (INIS)

    Ceremuzynski, L.K.; Klos, J.; Barcikowski, B.; Herbaczynska-Cedro, K.

    1991-01-01

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

    DEFF Research Database (Denmark)

    Lindhardt, Morten; Persson, Frederik; Currie, Gemma

    2016-01-01

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

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

    Science.gov (United States)

    Rodriguez-Padial, Luis; Akerström, Finn; Barderas, María G; Vivanco, Fernando; Arias, Miguel A; Segura, Julian; Ruilope, Luis M

    2017-12-08

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

  4. Active renin mass concentration to determine aldosterone-to-renin ratio in screening for primary aldosteronism

    Directory of Open Access Journals (Sweden)

    Corbin F

    2011-07-01

    Full Text Available François Corbin1, Pierre Douville2, Marcel Lebel3 1Division of Biochemistry, l'Université de Sherbrooke, Sherbrooke, Quebec, Canada; 2Division of Biochemistry; 3Division of Nephrology, L'Hôtel-Dieu de Québec Hospital and l'Université Laval, Quebec, CanadaBackground: Active renin mass concentration (ARC is independent of the endogenous level of angiotensinogen, and less variable and more reproducible than plasma renin activity. Reference values for the aldosterone-to-renin ratio (ARR using ARC are still undefined. The objective of the present study was to determine the threshold of ARR using ARC measurement to screen for primary aldosteronism.Methods: A total of 211 subjects were included in the study, comprising 78 healthy normotensive controls, 95 patients with essential hypertension, and 38 patients with confirmed primary aldosteronism (20 with surgery-confirmed aldosterone-producing adenoma and 18 with idiopathic adrenal hyperplasia. Blood samples were drawn from ambulatory patients and volunteers in the mid-morning without specific dietary restriction for measuring plasma aldosterone concentration, ARC, and serum potassium.Results: Most normotensive controls and essential hypertension patients had ARR results below 100 pmol/ng, a value which corresponded to 3.3 times the median of these two groups.Conclusion: Patients with ARR values above this level should be considered for further investigation (confirmatory tests or for repeat testing should ARR values be borderline. This study indicates that ARC can be used reliably in determining ARR for primary aldosteronism screening.Keywords: primary aldosteronism, active renin mass concentration, aldosterone-to-renin ratio

  5. Associations of aldosterone and renin concentrations with inflammation-the Study of Health in Pomerania and the German Conn's Registry.

    Science.gov (United States)

    Grotevendt, A; Wallaschofski, H; Reincke, M; Adolf, C; Quinkler, M; Nauck, M; Hoffmann, W; Rettig, R; Hannemann, A

    2017-08-01

    Chronic inflammation is an age-independent and body mass index-independent contributor to the development of multi-morbidity. Alterations of the renin-angiotensin-aldosterone system are observed within the context of proinflammatory states. We assessed circulating aldosterone, renin, and inflammatory biomarker concentrations in healthy, normotensive subjects and patients with primary aldosteronism. We included 1177 normotensive individuals from the population-based Study of Health in Pomerania (first follow-up, Study of Health in Pomerania-1) and 103 primary aldosteronism patients from the German Conn's Registry. A 1:1 matching for sex, age, body mass index, smoking status, diabetes mellitus, and the estimated glomerular filtration rate was performed to determine whether primary aldosteronism patients exhibit higher inflammatory biomarker concentrations than normotensive controls. The associations of plasma aldosterone concentration or plasma renin concentration with circulating fibrinogen concentrations, white blood cell count, and high sensitive C-reactive protein concentrations in the normotensive sample were determined with multivariable linear and logistic regression analyses. 1:1 matched primary aldosteronism patients demonstrated significantly (p < 0.01) higher plasma aldosterone concentration (198 vs. 47 ng/l), lower plasma renin concentration (3.1 vs. 7.7 ng/l) and higher high sensitive C-reactive protein concentrations (1.5 vs. 1.0 mg/l) than normotensive controls. Within the normotensive cohort, plasma renin concentration but not plasma aldosterone concentration was positively associated with fibrinogen concentrations and white blood cell count. Further, a J-shaped association between plasma renin concentration and high sensitive C-reactive protein concentrations was detected. High plasma aldosterone concentration in a primary aldosteronism cohort and high plasma renin concentration in normotensive subjects are associated with increased

  6. The renin-angiotensin system in kidney development

    DEFF Research Database (Denmark)

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

    2004-01-01

    Recent data from studies in rodents with targeted gene disruption and pharmacological antagonists have shown that the renin-angiotensin-aldosterone system (RAAS) and cyclooxygenase type-2 (COX-2) are necessary for late stages of kidney development. The present review summarizes data on the develo......Recent data from studies in rodents with targeted gene disruption and pharmacological antagonists have shown that the renin-angiotensin-aldosterone system (RAAS) and cyclooxygenase type-2 (COX-2) are necessary for late stages of kidney development. The present review summarizes data...... on the developmental changes of RAAS and COX-2 and the pathways by which they are activated; their possible interplay and the mechanisms by which they affect kidney development. Intrarenal and circulating renin and angiotensin II (ANG II) are stimulated at birth in most mammals. In rats, renin and ANG II stay...... glucocorticoid concentration and by a low NaCl intake. Studies with selective inhibitors of COX-2 and COX-2 null mice show that COX-2 activity stimulates renin secretion from JG-cells during postnatal kidney development and that lack of COX-2 activity leads to pathological change in cortical architecture...

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

    Science.gov (United States)

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

    2018-04-03

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

  8. 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.

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

    NARCIS (Netherlands)

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

    2002-01-01

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

  10. Biochemical monitoring after initiation of aldosterone antagonist therapy in users of renin-angiotensin system blockers: a UK primary care cohort study.

    Science.gov (United States)

    Sinnott, Sarah-Jo; Mansfield, Kathryn E; Schmidt, Morten; Bhaskaran, Krishnan; Smeeth, Liam; Nitsch, Dorothea; Tomlinson, Laurie A

    2017-11-16

    To determine the frequency of biochemical monitoring after initiation of aldosterone antagonists(AA) in patients also using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB). UK primary care. ACEI/ARB users who initiated AA between 2004 and 2014. We calculated the proportions with: (1) biochemical monitoring ≤2 weeks post initiation of AA, (2) adverse biochemical values ≤2 months (potassium ≥6 mmol/L, creatinine ≥220 µmol/L and ≥30% increase in creatinine from baseline) and (3) discontinuers of AA in those with an adverse biochemical value. We used logistic regression to study patient characteristics associated with monitoring and adverse biochemical values. In 10 546 initiators of AA, 3291 (31.2%) had a record of biochemical monitoring ≤2 weeks post initiation. A total of 2.0% and 2.7% of those with follow-up monitoring within 2 months of initiation experienced potassium ≥6 mmol/L and creatinine ≥220 µmol/L, respectively, whereas 13.5% had a ≥30% increase in creatinine. Baseline potassium (OR 3.59, 95% CI 2.43 to 5.32 for 5.0-5.5 mmol/L compared with monitoring within 2 weeks of initiating AAs. Higher levels of monitoring may reduce adverse biochemical events. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. The Renal Renin-Angiotensin System

    Science.gov (United States)

    Harrison-Bernard, Lisa M.

    2009-01-01

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

  12. Polymorphisms of three genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system are not associated with blood pressure salt sensitivity: A systematic meta-analysis.

    Science.gov (United States)

    Sun, Jiahong; Zhao, Min; Miao, Song; Xi, Bo

    2016-01-01

    Many studies have suggested that polymorphisms of three key genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system (RAAS) play important roles in the development of blood pressure (BP) salt sensitivity, but they have revealed inconsistent results. Thus, we performed a meta-analysis to clarify the association. PubMed and Embase databases were searched for eligible published articles. Fixed- or random-effect models were used to pool odds ratios and 95% confidence intervals based on whether there was significant heterogeneity between studies. In total, seven studies [237 salt-sensitive (SS) cases and 251 salt-resistant (SR) controls] for ACE gene I/D polymorphism, three studies (130 SS cases and 221 SR controls) for AGT gene M235T polymorphism and three studies (113 SS cases and 218 SR controls) for CYP11B2 gene C344T polymorphism were included in this meta-analysis. The results showed that there was no significant association between polymorphisms of these three polymorphisms in the RAAS and BP salt sensitivity under three genetic models (all p > 0.05). The meta-analysis suggested that three polymorphisms (ACE gene I/D, AGT gene M235T, CYP11B2 gene C344T) in the RAAS have no significant effect on BP salt sensitivity.

  13. Comparative biochemistry of renins and angiotensins in the vertebrates.

    Science.gov (United States)

    Nakajima, T; Khosla, M C; Sakakibara, S

    1978-09-01

    Comparative biochemistry of renins and angiotensins was discussed. Renin extracted from hog kidney was different from that from mouse submaxillary glands in immunoreactivity and carbohydrate content. Rat kidney renin was also different from hog kidney renin in the amino acid composition. The presence of big and big-big renins was pointed out immunochemically. These big renins were considered to be precursors of kidney renin. Angiotensins in mammalian and nonmammalian species produced by renal or extrarenal renin have been differentiated by some biochemical and pharmacological criteria. Some of these angiotensins were analyzed sequentially. The replacements of amino acid residues at positions 1, 5, and/or 9 of angiotensin I have been demonstrated in nonmammalian species. Specific pressor activities have been determined using synthetic angiotensins by a 4 point assay in rat. Specific pressor activities of various angiotensins were obtained from the dose-blood pressure-response curves using a single angiotensin sample per assay rat.

  14. 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)

    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

  15. Renin-Angiotensin System in Diabetes.

    Science.gov (United States)

    Rein, Johannes; Bader, Michael

    2017-11-17

    The renin-angiotensin system (RAS) has two different axes, the classical one with the effector peptide angiotensin II and the new one with the effector peptide angiotensin (1-7). Both peptides have been shown to be involved in the pathogenesis of diabetes mellitus and its consequences, nephropathy, retinopathy and cardiomyopathy in animal models and patients. In diabetes, angiotensin II acts mostly deleterious and angiotensin (1-7) protective. In this review we summarize the knowledge about the role of the different RAS axes in diabetes mellitus and the use of drugs interfering with the RAS in the therapy of the disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    DEFF Research Database (Denmark)

    understanding of the protective side of the Renin Angiotensin System (RAS) involving angiotensin AT2 receptor, ACE2, and Ang(1-7)/Mas receptor Combines the knowledge of editors who pioneered research on the protective renin angiotensin system including; Dr. Thomas Unger, one of the founders of AT2 receptor......The Protective Arm of the Renin Angiotensin System: Functional Aspects and Therapeutic Implications is the first comprehensive publication to signal the protective role of a distinct part of the renin-angiotensin system (RAS), providing readers with early insight into a complex system which...... will become of major medical importance in the near future. Focusing on recent research, The Protective Arm of the Renin Angiotensin System presents a host of new experimental studies on specific components of the RAS, namely angiotensin AT2 receptors (AT2R), the angiotensin (1-7) peptide with its receptor...

  17. Effect of postural changes on aldosterone to plasma renin ratio in patients with suspected secondary hypertension.

    Science.gov (United States)

    Barigou, M; Ah-Kang, F; Orloff, E; Amar, J; Chamontin, B; Bouhanick, B

    2015-06-01

    To study the influence of postural changes on aldosterone to renin ratio (ARR) in patients with suspected secondary hypertension and to evaluate the sensitivity and specificity of the recommended seated ARR compared to supine and upright ARR for primary aldosteronism screening. Fifty-three hypertensive patients were prospectively hospitalized for secondary hypertension exploration (age: 51 ± 12, 66% males). After withdrawal of drugs interfering with renin angiotensin system, plasma aldosterone and direct renin concentration were measured in the morning, at bed after an overnight supine position, then out of bed after 1 hour of upright position and finally 2 hours later after 15 minutes of seating. Minimal renin value was set at 5 μUI/mL. Referring to ARR cut-off of 23 pg/μUI, the sensitivity of seated ARR was 57.1% and specificity was 92.3%. The negative and positive predictive values were 95.1% and 45.2% respectively. Compared to these results, a cut-off of 19 improved sensitivity to 85.7% with a specificity of 89.7%. Negative and positive predictive values were 98.3% and 41.1% respectively. Seated ARR mean value was lower than supine and upright ARR mean values, due to an overall increase in renin at seating compared to the supine position by factor 1.9 while aldosterone just slightly increased by factor 1.2. Seated ARR correlated to supine and upright ARR: correlation coefficients (r) 0.90 and 0.93 respectively (P<0.001). Current recommended measurement of ARR in the seating position is fairly correlated to supine and upright ARR. A suggested cut-off value of 19 instead of 23 pg/μUI increased the discriminating power of this test. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  18. Radioimmunoassay - renin - angiotensin. Principles of radioimmunoassay and their application in measuring renin and angiotensin

    Energy Technology Data Exchange (ETDEWEB)

    Krause, D K; Hummerich, W; Poulsen, K [eds.

    1978-01-01

    Typical pitfalls such as impurity of 'standard', tracer damage, crossreactivity of antiserum, unspecific binding of protecting proteins, blank effects with negative results, charcoal stripping, invisible coprecipitate or uncertainty in the analysis of the calibration curve (graph, logit-log, polynormal or spline function) can occur in any type of radioimmunoassay; they are detailed in the general part of this book. The special position occupied by radioimmunological quantification of parameters of the renin-angiotensin system creates additional, even more serious problems. While the radioimmunological determination of the decapeptide angiotensin I no longer causes major obstacles, measurement of the biologically active octapeptide angiotensin II is still only possible in a few centers. The (indirect) determination of plasma renin is characterized by a situation where the enzyme renin may be clearly defined in theory as a specific 10-11-leucine-leucine-endopeptidase cleaving only a decapeptide, but the actual renin assay, however, measures various forms of renin and other angiotensin-forming (or angiotensin-destroying) enzymes at the same time.

  19. 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.

  20. 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.

  1. Cortisol-induced inhibition of ovine renin and aldosterone responses to hypotension

    International Nuclear Information System (INIS)

    Wood, C.E.; Silbiger, J.

    1987-01-01

    Previous studies from this laboratory have demonstrated that in preterm fetal sheep increases in plasma cortisol (F) concentration equal in amplitude to fetal F stress responses suppress plasma renin activity (PRA). The purpose of this study was to investigate the possibility that this negative interaction exists in adult sheep. Cortisol was measured by radioimmunoassay. Five conscious ewes with chronically prepared carotid arterial loops were infused intravenously with F or vehicle for 5 h. One hour after the end of F or vehicle infusion, renin secretion was stimulated by hypotension produced by infusion of sodium nitroprusside. F infusion increased plasma F; during vehicle infusion plasma F did not change. F infusion decreased hematocrit from 29 +/- 2 to 26 +/- 1%. Basal PRA in vehicle- and F-infused groups were 0.4 +/- 0 and 0.2 +/- 0.1 ng angiotensin I-ml -1 -h -1 and did not change. In vehicle-infused ewes, PRA increased from 0.4 +/- 0 to 4.6 +/- 0.4 and plasma aldosterone from 26.0 +/- 1.0 to 173.1 +/- 21.8 pg/ml, while in F-infused ewes, PRA increased from 0.2 +/- 1 to 3.3 +/- 0.4 ng angiotensin I-ml -1 -h -1 and aldosterone from 25.0 +/- 0 to 48.2 +/- 23.2 pg/ml, significantly smaller responses. These results suggest that repeated stress may modulate the responses of the renin-angiotensin system in this species

  2. 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 valsartan. Baseline ln(aldosterone) correlated with 24-hour systolic and diastolic BP reductions following combination treatment only (P < .001 and P = .005). The implications of the renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. The evolution of renin-angiotensin blockade: angiotensin-converting enzyme inhibitors as the starting point.

    Science.gov (United States)

    Sica, Domenic A

    2010-04-01

    The renin-angiotensin system has been a target in the treatment of hypertension for close to three decades. Several medication classes that block specific aspects of this system have emerged as useful therapies, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and, most recently, direct renin inhibitors. There has been a natural history to the development of each of these three drug classes, starting with their use as antihypertensive agents; thereafter, in each case they have been employed as end-organ protective agents. To date, there has been scant evidence to favor angiotensin receptor blockers or direct renin inhibitors over angiotensin-converting enzyme inhibitors in treating hypertension or in affording end-organ protection; thus, angiotensin-converting enzyme inhibitors remain the standard of care when renin-angiotensin system blockade is warranted.

  4. Anthology of the renin-angiotensin system: a one hundred reference approach to angiotensin II antagonists.

    Science.gov (United States)

    Ménard, J

    1993-04-01

    To provide a historical overview of the renin-angiotensin system as a guide to the introduction of a new therapeutic pathway, non-peptide inhibition of a angiotensin II. One hundred references were selected as a personal preference, for their originality or for their potential impact on medicine. This review raises the following questions for future research. (1) Will the long-term cardiovascular effects of angiotensin converting enzyme (ACE) inhibition, angiotensin II antagonism and renin inhibition be similar or not, and dependent or independent of blood pressure levels? (2) What are the local-regional interactions between vasoconstrictor and vasodilator systems, and does the renin-angiotensin system synchronize these regional hemodynamic regulatory mechanisms? (3) If hypertension is the result of an interaction between genetic and environmental factors, do proteins secreted through constitutive pathways contribute to the genetic abnormality (prorenin, angiotensinogen, ACE) while regulated secretion (renin) and other regulatory mechanisms (angiotensin II receptors) provide biological support for the environmental effects?

  5. Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone study

    Directory of Open Access Journals (Sweden)

    McInnes Gordon T

    2007-05-01

    Full Text Available Abstract Background High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT1study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study. The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting. Methods/design The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios. Primary Objective – To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios. Secondary Objectives – To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement

  6. High maternal sodium intake alters sex-specific renal renin-angiotensin system components in newborn Wistar offspring.

    Science.gov (United States)

    Maia, D R R; Lopes, K L; Heimann, J C; Furukawa, L N S

    2016-01-28

    This study aimed to evaluate the systemic and renal renin-angiotensin-aldosterone system (RAAS) at birth in male and female offspring and in mothers fed a high sodium diet (HSD) before and during gestation. Female Wistar rats were fed a HSD (8.0% NaCl) or a normal sodium diet (1.3% NaCl) from 8 weeks of age until delivery of their first litter. Maternal body weight, tail blood pressure, and food and water intake were evaluated. The litter sizes were assessed, and the body and kidney weights of the offspring were measured. Both mothers and offspring were euthanized immediately following the birth of the pups to evaluate plasma renin activity (PRA), renal renin content (RRC), renal angiotensin-converting enzyme (ACE) activity, renal angiotensin (Ang) II content, serum aldosterone (ALDO) levels, and renal cortical and medullary renin messenger RNA expression. In mothers in the HSD group, water intake and kidney mass were higher, whereas renal ACE activity, Ang II, PRA, ALDO and RRC were decreased. In the offspring of HSD-fed dams, the body and kidney mass were lower in both genders, renal ACE activity was lower in females and renal Ang II was lower in males. PRA, RRC, renin gene expression and ALDO levels did not differ between the groups of offspring. The data presented herein showed that a maternal HSD during pregnancy induces low birth weight and a sex-specific response in the RAAS in offspring.

  7. Effects of single and repeated doses of the calcium antagonist felodipine on blood pressure, renal function, electrolytes and water balance, and renin-angiotensin-aldosterone system in hypertensive patients.

    Science.gov (United States)

    Leonetti, G; Gradnik, R; Terzoli, L; Fruscio, M; Rupoli, L; Cuspidi, C; Sampieri, L; Zanchetti, A

    1986-01-01

    Doses of 10 mg b.i.d. of the new dihydropyridine calcium antagonist, felodipine, were tested for seven consecutive days in 11 hospitalized hypertensive patients. A significant reduction of both systolic and diastolic blood pressures, with patients in both the supine and upright positions, occurred immediately after the first dose and was maintained (daily average 15%) throughout the following days. An increase in heart rate was observed after the first dose (15 and 23 beats/min, in supine and upright postures), and subsequently declined to average values of 8 and 14 beats/min on the seventh day. There was a marked natriuretic response during the first and second day, during which an average negative sodium balance of 95 mmol developed; on the following days sodium output was not significantly different from control, but a negative balance averaging 135 mmol was still present on the seventh day of felodipine administration. A moderate negative potassium balance also progressively developed and reached -48 mmol on the seventh day. Glomerular filtration rate was unchanged, but renal plasma flow increased significantly during administration of felodipine. Plasma renin activity and plasma aldosterone were also increased very moderately by felodipine. Compared with previous observations by our group with higher doses of felodipine (12.5, 25, and 50 mg t.i.d.), 10 mg b.i.d. of this new calcium antagonist appear to exert a marked and prolonged blood pressure reduction, accompanied by a definite natriuretic instead of an antinatriuretic effect.

  8. The role of renin angiotensin system in retinal inflammation

    OpenAIRE

    Zhu, Tong

    2017-01-01

    Purpose: Retinopathy of prematurity (ROP) is the main cause of vision loss and blindness in children, and is replicated and intensively studied in rodent models of oxygen-induced retinopathy (OIR). One signature feature of ROP is retinal neovascularization, which is also present in patients with proliferative diabetic retinopathy (PDR). Inflammation is another feature in ROP and PDR. In both diseases, the renin angiotensin system (RAS) is dysregulated, and blockade of RAS via angiotensin II (...

  9. Effects of gender on screening value of aldosterone-renin ratio for primary aldosteronism

    Directory of Open Access Journals (Sweden)

    Ye-qiong SONG

    2017-02-01

    Full Text Available Objective To explore the potential influence of gender on screening value of aldosterone-renin ratio (ARR for primary aldosteronism (PA. Methods The biochemical parameters were collected of 451 PA patients and 300 essential hypertension (EH patients who were diagnosed in the General Hospital of PLA from 1992 to 2014. Each group was then divided into two groups by gender. The clinical characteristics were compared and then the receiver operating characteristic curve (ROC was conducted to evaluate the best cut-off value. Results The plasma aldosterone concentration (PAC, serum sodium and ARR were much higher, but the plasma rennin activity (PRA, serum potassium and BMI were much lower in PA patients than in EH patients (P0.05. The best cut-off value of ARR in male PA patients was 19.11, the relevant area under the curve (AUC was 0.968, the sensitivity and specificity was 92.44% and 93.08%, and the Youden index (YI was 0.86. The best cut-off value of ARR in female PA patients was 27.26, with AUC 0.956, sensitivity 92.07%, specificity 90.00% and YI 0.82, respectively. If the cut-off value was set at 27.26 in males, the specificity would rise a little, but the sensitivity and YI would sharply decrease. Similarly, the sensitivity would increase a little but the specificity and YI would fall substantially if the cut-off value in females was set at 19.11. The best cut-off value of ARR in men was smaller than the official value recommended by guidelines. Conclusion Gender is an important factor should be considered while ARR is used in PA screening, and the cut-off value of ARR in screening female PA patients should be setting higher. DOI: 10.11855/j.issn.0577-7402.2017.01.10

  10. Outcome of Venom Bradykinin Potentiating Factor on Renin Angiotensin System in Irradiated Rats

    International Nuclear Information System (INIS)

    Ashry, O.; Farouk, H.; Moustafa, M.; Abu Sinn, G.; Abd ElBaset, A.

    2011-01-01

    Scorpion Venom contains a strong bradykinin potentiating factor (BPF) exhibiting angiotensin converting enzyme inhibition (ACEI). Irradiation and stimulation of renin-angiotensin system (RAS) induce oxidative stress. Interruption of the RAS by an ACEI or angiotensin II receptor blocker (ARB) losartan (LOS) and/or gamma-rays (4 Gy) were evaluated. Rats received 6 doses of BPF (1μg/g body wt) or of LOS (5 μg/g body wt). Treatment with BPF induced significant elevation in the level of potassium (K) and significant drop in the level of sodium (Na) and uric acid. Treatment with LOS significantly depressed the level of Na and uric acid compared to control. Irradiation discerned a significant elevation in malondialdehyde (MDA), advanced oxidative protein product (AOPP), aldosterone, Na, urea and creatinine, and a significant drop in the haematological values, glutathione (GSH), calcium (Ca) and uric acid. A significant decrease in MDA, aldosterone, urea, creatinine and uric acid compared to irradiated group was observed in irradiated treated groups. Irradiated animals treated with LOS showed a significant decrease in Na and chloride (Cl) compared to the irradiated group. Considerable amelioration of radiation-induced depression in haematopoiesis, improvement of oxidative stress and kidney function by BPF as ACEI or LOS as ARB are detected. Results add further identification to the properties of BPF

  11. Effect of Diuresis on Plasma Renin Activity and Aldosterone Concentration in Normal and Toxemic Pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Sung, H. K.; Lee, H. S.; Cho, S. S.; Koh, J. H.; Lee, J. K.; Kim, H. S. [Korea Atomic Emergy Research Institute, Seoul (Korea, Republic of)

    1973-03-15

    The changes of plasma renin activity, aldosterone concentration, serum sodium, and potassium levels were studied before and after the water loading followed by diuretics injection. The materials were: 13 non-, 11 normal-, and 11 toxemic pregnancy cases. The plasma renin activity and aldosterone concentration of the cord and postpartum blood were also measured. Following were the results: 1. The plasma renin activity was elevated significantly in normal pregnancy, and slightly in toxemic pregnancy. The serum sodium levels were decreased in pregnancy. 2. The plasma aldosterone concentration was slightly decreased in normal pregnancy, and slightly increased in toxemic pregnancy, however, statistically insignificant. 3. The plasma renin activity of the cord and postpartum blood were lower than those of pregnancy cases. 4. The changes of plasma renin activity after the diuretic administration showed an initial increase, which recovered within 2 hours. These changes were the least in normal pregnancy, and the most in toxemic pregnancy. 5. The changes of plasma aldosterone concentration after the diuretic administration were similar to those of plasma renin activity, although the variations were not so wide.

  12. Effect of Diuresis on Plasma Renin Activity and Aldosterone Concentration in Normal and Toxemic Pregnancy

    International Nuclear Information System (INIS)

    Sung, H. K.; Lee, H. S.; Cho, S. S.; Koh, J. H.; Lee, J. K.; Kim, H. S.

    1973-01-01

    The changes of plasma renin activity, aldosterone concentration, serum sodium, and potassium levels were studied before and after the water loading followed by diuretics injection. The materials were: 13 non-, 11 normal-, and 11 toxemic pregnancy cases. The plasma renin activity and aldosterone concentration of the cord and postpartum blood were also measured. Following were the results: 1. The plasma renin activity was elevated significantly in normal pregnancy, and slightly in toxemic pregnancy. The serum sodium levels were decreased in pregnancy. 2. The plasma aldosterone concentration was slightly decreased in normal pregnancy, and slightly increased in toxemic pregnancy, however, statistically insignificant. 3. The plasma renin activity of the cord and postpartum blood were lower than those of pregnancy cases. 4. The changes of plasma renin activity after the diuretic administration showed an initial increase, which recovered within 2 hours. These changes were the least in normal pregnancy, and the most in toxemic pregnancy. 5. The changes of plasma aldosterone concentration after the diuretic administration were similar to those of plasma renin activity, although the variations were not so wide.

  13. The renin-angiotensin system and its blockers

    Directory of Open Access Journals (Sweden)

    Igić Rajko

    2014-01-01

    Full Text Available Research on the renin-angiotensin system (RAS has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of cardiovascular diseases. This review offers a brief history of the RAS with an overview of its major components and their functions, as well as blockers of the RAS, their clinical usage and current research that targets various components of the RAS. Because angiotensin-converting enzyme (ACE metabolizes two biologically active peptides, one in the kallikrein-kinin system (KKS and one in the RAS, it is the essential connection between the two systems. ACE releases very powerful hypertensive agent, angiotensin II and also inactivates strong hypotensive peptide, bradykinin. Inhibition of ACE thus has a dual effect, resulting in decreased angiotensin II and increased bradykinin. We described the KKS as well.

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

    OpenAIRE

    Yoon, Hye Eun; Choi, Bum Soon

    2014-01-01

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

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

    Science.gov (United States)

    Haber, E.

    1975-01-01

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

  16. Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy.

    Science.gov (United States)

    Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

    1999-01-01

    We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.

  17. 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.

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  19. Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension.

    Science.gov (United States)

    Shim, Kwang Yong; Eom, Young Woo; Kim, Moon Young; Kang, Seong Hee; Baik, Soon Koo

    2018-05-01

    The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1-7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1-7)/Mas receptor and ACE2/Ang-(1-9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension. Patients with portal hypertension have been treated with RAS antagonists such as ACE inhibitors, Ang receptor blockers, and aldosterone antagonists, with very promising hemodynamic results. In this review, we examine the RAS, its roles in hepatic fibrosis and portal hypertension, and current therapeutic approaches based on the use of RAS antagonists in patients with portal hypertension.

  20. Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Yavuz Beyazit

    2011-01-01

    Full Text Available Local hematopoietic bone marrow (BM renin-angiotensin system (RAS affects the growth, production, proliferation differentiation, and function of hematopoietic cells. Angiotensin II (Ang II, the dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R, has considerable proinflammatory and proatherogenic effects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis.

  1. Graz Endocrine Causes of Hypertension (GECOH study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism

    Directory of Open Access Journals (Sweden)

    Dobnig Harald

    2009-04-01

    Full Text Available Abstract Background Primary aldosteronism (PA affects approximately 5 to 10% of all patients with arterial hypertension and is associated with an excess rate of cardiovascular complications that can be significantly reduced by a targeted treatment. There exists a general consensus that the aldosterone to renin ratio should be used as a screening tool but valid data about the accuracy of the aldosterone to renin ratio in screening for PA are sparse. In the Graz endocrine causes of hypertension (GECOH study we aim to prospectively evaluate diagnostic procedures for PA. Methods and design In this single center, diagnostic accuracy study we will enrol 400 patients that are routinely referred to our tertiary care center for screening for endocrine hypertension. We will determine the aldosterone to active renin ratio (AARR as a screening test. In addition, all study participants will have a second determination of the AARR and will undergo a saline infusion test (SIT as a confirmatory test. PA will be diagnosed in patients with at least one AARR of ≥ 5.7 ng/dL/ng/L (including an aldosterone concentration of ≥ 9 ng/dL who have an aldosterone level of ≥ 10 ng/dL after the saline infusion test. As a primary outcome we will calculate the receiver operating characteristic curve of the AARR in diagnosing PA. Secondary outcomes include the test characteristics of the saline infusion test involving a comparison with 24 hours urine aldosterone levels and the accuracy of the aldosterone to renin activity ratio in diagnosing PA. In addition we will evaluate whether the use of beta-blockers significantly alters the accuracy of the AARR and we will validate our laboratory methods for aldosterone and renin. Conclusion Screening for PA with subsequent targeted treatment is of great potential benefit for hypertensive patients. In the GECOH study we will evaluate a standardised procedure for screening and diagnosing of this disease.

  2. Renin-aldosterone-sodium profiling in hypertensive Filipinos. Pt. 2

    International Nuclear Information System (INIS)

    Guevara, R.; Torres, J. Jr; Abundo, H.P.; Perez, A.P.; Ochoa, W.K.

    1981-01-01

    Plasma renin activity determination by radioimmunoassay as profiling technique is a useful guide for more rational and precise treatment of hypertension. Statistical nomograms are developed for normals, essential hypertension, diabetic hypertension, renal diseases, renal disease and dialysis, normal pregnancy, toxemic pregnancy and contraceptive pill users with and without hypertension. (orig.) [de

  3. Renin-aldosterone-sodium profiling in hypertensive Filipinos. Pt. 2

    Energy Technology Data Exchange (ETDEWEB)

    Guevara, R.; Torres, J. Jr; Abundo, H.P.; Perez, A.P.; Ochoa, W.K.

    1981-10-01

    Plasma renin activity determination by radioimmunoassay as profiling technique is a useful guide for more rational and precise treatment of hypertension. Statistical nomograms are developed for normals, essential hypertension, diabetic hypertension, renal diseases, renal disease and dialysis, normal pregnancy, toxemic pregnancy and contraceptive pill users with and without hypertension.

  4. Renin-aldosterone-sodium profiling in normal Filipinos. Pt. 1

    International Nuclear Information System (INIS)

    Guevara, R.; Torres, J. Jr.; Abundo, H.P.; Perez, A.P.; Ochoa, W.K.

    1981-01-01

    Plasma renin activity determination by radioimmunoassay is feasible, accurate, reproducible and reliable. This profiling technic is a very useful guide for more rational and precise treatment of the hypertensive state, but even when profiling cannot be done, statistical nomograms can be useful, just as well, as a guide in the treatment of hypertewnsion. (orig.) [de

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

    Science.gov (United States)

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

    2015-08-01

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

  6. Expression of Angiotensin II and Aldosterone in Radiation-induced Lung Injury.

    Science.gov (United States)

    Cao, Shuo; Wu, Rong

    2012-12-01

    Radiation-induced lung injury (RILI) is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILI was studied. Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-β1, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI.

  7. Expression of Angiotensin II and Aldosterone in Radiation-induced Lung Injury

    International Nuclear Information System (INIS)

    Cao, Shuo; Wu, Rong

    2012-01-01

    Radiation-induced lung injury (RILI) is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILI was studied. Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-β1, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI

  8. New Frontiers in the Intrarenal Renin-Angiotensin System: A Critical Review of Classical and New Paradigms

    Science.gov (United States)

    Zhuo, Jia L.; Ferrao, Fernanda M.; Zheng, Yun; Li, Xiao C.

    2013-01-01

    The renin-angiotensin system (RAS) is well-recognized as one of the oldest and most important regulators of arterial blood pressure, cardiovascular, and renal function. New frontiers have recently emerged in the RAS research well beyond its classic paradigm as a potent vasoconstrictor, an aldosterone release stimulator, or a sodium-retaining hormone. First, two new members of the RAS have been uncovered, which include the renin/(Pro)renin receptor (PRR) and angiotensin-converting enzyme 2 (ACE2). Recent studies suggest that prorenin may act on the PRR independent of the classical ACE/ANG II/AT1 receptor axis, whereas ACE2 may degrade ANG II to generate ANG (1–7), which activates the Mas receptor. Second, there is increasing evidence that ANG II may function as an intracellular peptide to activate intracellular and/or nuclear receptors. Third, currently there is a debate on the relative contribution of systemic versus intrarenal RAS to the physiological regulation of blood pressure and the development of hypertension. The objectives of this article are to review and discuss the new insights and perspectives derived from recent studies using novel transgenic mice that either overexpress or are deficient of one key enzyme, ANG peptide, or receptor of the RAS. This information may help us better understand how ANG II acts, both independently or through interactions with other members of the system, to regulate the kidney function and blood pressure in health and disease. PMID:24273531

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

    Science.gov (United States)

    Yoon, Hye Eun; Choi, Bum Soon

    2014-05-01

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

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

    African Journals Online (AJOL)

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

  11. Brain renin angiotensin system in cardiac hypertrophy and failure

    Directory of Open Access Journals (Sweden)

    Luciana eCampos

    2012-01-01

    Full Text Available Brain renin-angiotensin system (RAS is significantly involved in the roles of the endocrine RAS in cardiovascular regulation. Our studies indicate that the brain RAS participates in the development of cardiac hypertrophy and fibrosis through sympathetic activation. Inhibition of sympathetic hyperactivity after myocardial infarction through suppression of the brain RAS appears beneficial. The brain RAS is involved in the modulation of circadian rhythms of arterial pressure, contributing to nondipping hypertension. We conclude that the brain RAS in pathophysiological states interacts synergistically with the chronically overactive RAS through a positive biofeedback in order to maintain a state of alert diseased conditions, such as cardiac hypertrophy and failure. Therefore, targeting brain RAS with drugs such as angiotensin converting inhibitors or receptor blockers having increased brain penetrability could be of advantage. These RAS-targeting drugs are first-line therapy for all heart failure patients. Since the RAS has both endocrine and local tissue components, RAS drugs are being developed to attain increased tissue penetrability and volume of distribution and consequently an efficient inhibition of both RAS components.

  12. Prevention of atrial fibrillation by Renin-Angiotensin system inhibition a meta-analysis

    DEFF Research Database (Denmark)

    Schneider, Markus; Hua, Tsushung A; Böhm, Michael

    2010-01-01

    The authors reviewed published clinical trial data on the effects of renin-angiotensin system (RAS) inhibition for the prevention of atrial fibrillation (AF), aiming to define when RAS inhibition is most effective.......The authors reviewed published clinical trial data on the effects of renin-angiotensin system (RAS) inhibition for the prevention of atrial fibrillation (AF), aiming to define when RAS inhibition is most effective....

  13. RENIN ANGIOTENSIN SYSTEM GENE POLYMORPHISMS IN CHILDREN WITH NEPHROTIC SYNDROM

    Directory of Open Access Journals (Sweden)

    Zh.P. Sharnova

    2006-01-01

    Full Text Available To investigate the role of the reninangiotensin system genes polymorphisms in develop and progression of nephrotic syndrom (NS in children we determined the genotypes of angiotensin converting enzyme (ACE, angiotensinogen (AGT and angiotensin ii receptor (ATII-R of 1 type in 80 russian children with ns including and 15 children with chronic renal failure (CRF. Genotype frequencies did not differ between patients with ns and controls (n = 165. The distribution of ace, AGT and ATII-R 1 type genotypes was similar among ns sub groups, such as focal segmental glomerulosclerosis (FSGS (n = 18, steroid-sensitive nephrotic syndrome (n = 32, nephrotic syndrome with hypertension and hemoturia (n = 22 and with control group. When ns subjects with CRF (n = 15 were compared with control, the prevalence of ace DD genotype was significantly higher (47% VS 21%; χ2 = 4,44; p < 0,05. Our results indicate that the DD genotype ace may be a factor of risk for the dеvеlopment of progressive renal impairment in the children with nephrotic syndrome. The analysis of treatment's effect with inhibitor of ace in groups patients with steroid resistant NS (SRNS demonstrated decreasing of renoprotective effect of this drugs in patients with id and dd genotypes com? Pared with ii genotype: the degree of blood pressure, proteinuria and the rate of glomerular filtration decrease was significantly lower (55,46 ± 9,25 VS 92,74 ± 25; р < 0,05 in these patients.Key words: nephrotic syndrom, chronic renal failure, polymorphism of genes, renin-angiotensin system.

  14. Renin angiotensin system and gender differences in dopaminergic degeneration

    Directory of Open Access Journals (Sweden)

    Rodriguez-Perez Ana I

    2011-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-01

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

  16. Obstructive Sleep Apnea and Aldosterone

    Science.gov (United States)

    Svatikova, Anna; Olson, Lyle J.; Wolk, Robert; Phillips, Bradley G.; Adachi, Taro; Schwartz, Gary L.; Somers, Virend K.

    2009-01-01

    Background: Obstructive sleep apnea (OSA) is a major risk factor for hypertension and has been associated with increased risk for cardiovascular morbidity. A dysregulated renin-angiotensin-aldosterone system may contribute to excess sodium retention and hypertension and may be activated in OSA. We tested the hypothesis that serum levels of aldosterone and plasma renin activity (PRA) are increased by apneic sleep in subjects without cardiovascular disease, compared to healthy control subjects. Methods and Results: Plasma aldosterone level was measured in 21 subjects with moderate to severe OSA and was compared to 19 closely matched healthy subjects. Plasma renin activity (PRA) was measured in 19 OSA patients and in 20 healthy controls. Aldosterone and PRA were measured before sleep (9pm), after 5 hrs of untreated OSA (2am) and in the morning after awakening (6am). There were no baseline (9pm) differences in serum aldosterone levels and PRA between the healthy controls and OSA patients (aldosterone: 55.2 ± 9 vs 56.0 ± 9 pg/mL; PRA: 0.99 ± 0.15 vs 1.15 ± 0.15 ng/mL/hr). Neither several hours of untreated severe OSA nor CPAP treatment affected aldosterone levels and PRA in OSA patients. Diurnal variation of both aldosterone and PRA was observed in both groups, in that morning renin and aldosterone levels were higher than those measured at night before sleep. Conclusions: Our study shows that patients with moderate to severe OSA without co-existing cardiovascular disease have plasma aldosterone and renin levels similar to healthy subjects. Neither untreated OSA nor CPAP treatment acutely affect plasma aldosterone or renin levels. Citation: Svatikova A; Olson LJ; Wolk R; Phillips BG; Adachi T; Schwartz GL; Somers VK. Obstructive sleep apnea and aldosterone. SLEEP 2009;32(12):1589-1592. PMID:20041594

  17. 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.......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....

  18. Dexamethasone-responsive hypertension in young women with suppressed renin and aldosterone

    International Nuclear Information System (INIS)

    Hoefnagels, W.H.L.; Hofman, J.A.; Smals, A.G.H.; Drayer, J.I.M.; Kloppenborg, P.W.C.; Benraad, T.J.

    1978-01-01

    Pronounced hypoaldosteronism was found in three young women with hypertension and symptoms of mineralocorticoid overproduction - i.e., hyporeninaemia, hypokalaemia, and a fall in blood-pressure after diuretic therapy. Plasma 11-deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone concentrations were normal. Treatment with dexamethasone induced a return to normal of blood-pressure and plasma-potassium and an increase in plasma-renin activity and urinary aldosterone excretion. The data suggest that hypertension in these patients is maintained by overproduction of an unknown adrenocorticotropin-dependent mineralocortocoid. (author)

  19. Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.

    Science.gov (United States)

    Kobori, H; Ichihara, A; Suzuki, H; Takenaka, T; Miyashita, Y; Hayashi, M; Saruta, T

    1997-08-01

    This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

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

    DEFF Research Database (Denmark)

    Gribouval, Olivier; Morinière, Vincent; Pawtowski, Audrey

    2012-01-01

    , pulmonary hypoplasia, and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), and AGTR1 (angiotensin II receptor type 1). Here, we review...... the series of 54 distinct mutations identified in 48 unrelated families. Most of them are novel and ACE mutations are the most frequent, observed in two-thirds of families (64.6%). The severity of the clinical course was similar whatever the mutated gene, which underlines the importance of a functional RAS...

  1. Aldosterone to Active Renin Ratio Is Associated With Nocturnal Blood Pressure in Obese and Treated Hypertensive Patients: The Styrian Hypertension Study

    NARCIS (Netherlands)

    Grubler, M.R.; Kienreich, K.; Gaksch, M.; Verheyen, N.; Fahrleitner-Pammer, A.; Schmid, J.; Grogorenz, J.; Ablasser, K.; Pieske, B.; Tomaschitz, A.; Pilz, S.

    2014-01-01

    High aldosterone levels are considered to play a key role in arterial hypertension. Data on the relationship between the aldosterone to active renin ratio (AARR), a quantity of aldosterone excess, and ambulatory blood pressure (BP) monitoring (ABPM) during the night are, however, sparse.

  2. Relationship Between Aldosterone and Parathyroid Hormone, and the Effect of Angiotensin and Aldosterone Inhibition on Bone Health

    DEFF Research Database (Denmark)

    L.S., Bislev; T., Sikjaer; L., Rolighed

    2015-01-01

    Emerging evidence suggests a stimulating effect of parathyroid hormone (PTH) on the reninnullangiotensinnullaldosterone system (RAAS). In primary hyperparathyroidism, chronic-elevated PTH levels seem to stimulate the RAAS which may explain the increased risk of cardiovascular disease (CVD......). In addition to increased PTH levels, low vitamin D levels may also directly increase risk of CVD, as vitamin D, itself, has been shown to inhibit the RAAS. Angiotensin II, aldosterone and cortisol all negatively impact bone health. Hyperaldosteronism is associated with a reversible secondary...... hyperparathyroidism due to increased renal calcium excretion. Moreover, the angiotensin II receptor is expressed by human parathyroid tissue, and angiotensin may therefore directly stimulates PTH secretion. An increased bone loss is found in patients with hyperaldosteronism. The angiotensin II receptor seems main...

  3. Plasma renin activity, aldosterone and catecholamine levels when swimming and running.

    Science.gov (United States)

    Guezennec, C Y; Defer, G; Cazorla, G; Sabathier, C; Lhoste, F

    1986-01-01

    The purpose of this study was to determine the response of plasma renin activity (PRA), plasma aldosterone concentration (PAC) and catecholamines to two graded exercises differing by posture. Seven male subjects (19-25 years) performed successively a running rest on a treadmill and a swimming test in a 50-m swimming pool. Each exercise was increased in severity in 5-min steps with intervals of 1 min. Oxygen consumption, heart rate and blood lactate, measured every 5 min, showed a similar progression in energy expenditure until exhaustion, but there was a shorter time to exhaustion in the last step of the running test. PRA, PAC and catecholamines were increased after both types of exercise. The PRA increase was higher after the running test (20.9 ng AngI X ml-1 X h-1) than after swimming (8.66 ng AngI X ml-1 X h-1). The PAC increase was slightly greater after running (123 pg X ml-1) than swimming (102 pg X ml-1), buth the difference was not significant. Plasma catecholamine was higher after the swimming test. These results suggest that the volume shift induced by the supine position and water pressure during swimming decreased the PRA response. The association after swimming compared to running of a decreased PRA and an enhanced catecholamine response rule out a strict dependence of renin release under the effect of plasma catecholamines and is evidence of the major role of neural pathways for renin secretion during physical exercise.

  4. Low plasma aldosterone despite normal plasma renin activity in uncomplicated type 1 diabetes mellitus : effects of RAAS stimulation

    NARCIS (Netherlands)

    Luik, PT; Kerstens, MN; Hoogenberg, K; Navis, GJ; Dullaart, RPF

    Background Data on levels and responsiveness of PRA and aldosterone in type 1 diabetes mellitus are conflicting. Earlier studies were not standardized with respect to the type of diabetes mellitus, the presence of diabetic complications or sodium intake. Therefore, we studied plasma renin activity

  5. Renin-angiotensin system antagonists, glomerular filtration rate and blood pressure

    Directory of Open Access Journals (Sweden)

    D.D. Ivanov

    2018-02-01

    Full Text Available The article deals with the mModern data on the influence of renin-angiotensin system blockers on the glomerular filtration rate, the level of arterial pressure and the outcome of chronic kidney disease. The strategy of  rennin-angiotensine blockade is offered to be changed depending on the criteria va­lues of glomerular filtration rate: a combination of inhibitors of angiotensin-converting enzyme + angiotensin receptors blo­ckers, monotherapy and drug withdrawal in glomerular filtration rate under 15–30 ml/min/m2. The formula BRIMONEL for treatment of chronic kidney disease is given.

  6. The effect of a heptapeptide angiotensin analogue on aldosterone secretion in the rabbit

    International Nuclear Information System (INIS)

    Neusy, A.J.; Steele, J.M. Jr.; Lowenstein, J.

    1980-01-01

    To investigate the effects of the heptapeptide analogue, 7 Ile A III on angiotensin II and angiotensin III, the mean blood pressure, the plasma reninactivity, and the plasma aldosteron concentration were measured under various circumstances (dexamethasan infusion, 7 Ile A III addition, bleeding). The measurements were carried out by means of RIA. The adrenal, renal, and vascular reactions to the competitive blockade are discussed with reference to the results obtained. (orig.) [de

  7. Radioimmunoassay for determination of blood aldosterone and renin in the diagnosis of some forms of arterial hypertension

    International Nuclear Information System (INIS)

    Khamidov, R.I.; Khalmuratova, R.A.; Sattarova, F.K.

    1987-01-01

    Aldosterone concentration and renin activity in the blood from the ulnar, inferior cava veins at the level of the 12th thoracic vertebra, the left and right renal veins were studied in 60 patients with arterial hypertension by means of a radioimmunoassay kits (France). The patients were divided into 4 groups: with primary and idiopathic hyperaldosteronism, renal-parenchymatous and essential arterial hypertension. The diagnosis of primary and idiopathic hyperaldosteronism was also confirmed by low blood renin activity. Renin activity in the peripheral venous blood was considerably elevated in renal-parenchymatous arterial hypertension and was normal in essential hypertension. Aldosterone concentration in the blood from the vena cava inferior and renal veins was 1.6-2-fold as high on the affected side as on the contralateral one

  8. Renal hemodynamics and renin-angiotensin system activity in humans with multifocal renal artery fibromuscular dysplasia.

    Science.gov (United States)

    van Twist, Daan J L; Houben, Alphons J H M; de Haan, Michiel W; de Leeuw, Peter W; Kroon, Abraham A

    2016-06-01

    Fibromuscular dysplasia (FMD) is the second most common cause of renovascular hypertension. Nonetheless, knowledge on the renal microvasculature and renin-angiotensin system (RAS) activity in kidneys with FMD is scarce. Given the fairly good results of revascularization, we hypothesized that the renal microvasculature and RAS are relatively spared in kidneys with FMD. In 58 hypertensive patients with multifocal renal artery FMD (off medication) and 116 matched controls with essential hypertension, we measured renal blood flow (Xenon washout method) per kidney and drew blood samples from the aorta and both renal veins to determine renin secretion and glomerular filtration rate per kidney. We found that renal blood flow and glomerular filtration rate in FMD were comparable to those in controls. Although systemic renin levels were somewhat higher in FMD, renal renin secretion was not elevated. Moreover, in patients with unilateral FMD, no differences between the affected and unaffected kidney were observed with regard to renal blood flow, glomerular filtration rate, or renin secretion. In men, renin levels and renin secretion were higher as compared with women. The renal blood flow response to RAS modulation (by intrarenal infusion of angiotensin II, angiotensin-(1-7), an angiotensin II type 1 receptor blocker, or a nitric oxide synthase blocker) was also comparable between FMD and controls. Renal blood flow, glomerular filtration, and the response to vasoactive substances in kidneys with multifocal FMD are comparable to patients with essential hypertension, suggesting that microvascular function is relatively spared. Renin secretion was not increased and the response to RAS modulation was not affected in kidneys with FMD.

  9. The Relevance of the Renin-Angiotensin System in the Development of Drugs to Combat Preeclampsia

    Directory of Open Access Journals (Sweden)

    Norikazu Ueki

    2015-01-01

    Full Text Available Preeclampsia is a hypertensive disorder that occurs during pregnancy. It has an unknown etiology and affects approximately 5–8% of pregnancies worldwide. The pathophysiology of preeclampsia is not yet known, and preeclampsia has been called “a disease of theories.” The central symptom of preeclampsia is hypertension. However, the etiology of the hypertension is unknown. In this review, we analyze the molecular mechanisms of preeclampsia with a particular focus on the pathogenesis of the hypertension in preeclampsia and its association with the renin-angiotensin system. In addition, we propose potential alternative strategies to target the renin-angiotensin system, which is enhanced during pregnancy.

  10. Erratum Aldosterone synthase C-344T, angiotensin II type 1 receptor ...

    Indian Academy of Sciences (India)

    Aldosterone synthase C-344T, angiotensin II type 1 receptor A1166C and 11-β hydroxysteroid dehydrogenase G534A gene polymorphisms and essential hypertension in the population of Odisha, India. Manisha Patnaik, Pallabi Pati, Surendra N. Swain, Manoj K. Mohapatra, Bhagirathi Dwibedi, Shantanu K. Kar.

  11. Aldosterone downregulates delayed rectifier potassium currents through an angiotensin type 1 receptor-dependent mechanism.

    Science.gov (United States)

    Lv, Yankun; Wang, Yanjun; Zhu, Xiaoran; Zhang, Hua

    2018-01-01

    We have previously shown that aldosterone downregulates delayed rectifier potassium currents (I Ks ) via activation of the mineralocorticoid receptor (MR) in adult guinea pig cardiomyocytes. Here, we investigate whether angiotensin II/angiotensin type 1 receptor (AngII/AT1R) and intracellular calcium also play a role in these effects. Ventricular cardiomyocytes were isolated from adult guinea pigs and incubated with aldosterone (1 μmol·L -1 ) either alone or in combination with enalapril (1 μmol·L -1 ), losartan (1 μmol·L -1 ), nimodipine (1 μmol·L -1 ), or BAPTA-AM (2.5 μmol·L -1 ) for 24 h. We used the conventional whole cell patch-clamp technique to record the I Ks component. In addition, we evaluated expression of the I Ks subunits KCNQ1 and KCNE1 using Western blotting. Our results showed that both enalapril and losartan, but not nimodipine or BAPTA-AM, completely reversed the aldosterone-induced inhibition of I Ks and its effects on KCNQ1/KCNE1 protein levels. Furthermore, we found that AngII/AT1R mediates the inhibitory effects of aldosterone on I Ks . Finally, the downregulation of I Ks induced by aldosterone did not occur secondarily to a change in intracellular calcium concentrations. Taken together, our findings demonstrate that crosstalk between MR and AT1R underlies the effects of aldosterone, and provide new insights into the mechanism underlying potassium channels.

  12. Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin-angiotensin system.

    Science.gov (United States)

    Wang, Lei; Zhu, Qing; Lu, Aihua; Liu, Xiaofen; Zhang, Linlin; Xu, Chuanming; Liu, Xiyang; Li, Haobo; Yang, Tianxin

    2017-09-01

    Butyrate, a short-chain fatty acid, is the end product of the fermentation of complex carbohydrates by the gut microbiota. Recently, sodium butyrate (NaBu) has been found to play a protective role in a number of chronic diseases. However, it is still unclear whether NaBu has a therapeutic potential in hypertension. The present study was aimed to investigate the role of NaBu in angiotensin II (Ang II)-induced hypertension and to further explore the underlying mechanism. Ang II was infused into uninephrectomized Sprague-Dawley rats with or without intramedullary infusion of NaBu for 14 days. Mean arterial blood pressure was recorded by the telemetry system. Renal tissues, serum samples, and 24-h urine samples were collected to examine renal injury and the regulation of the (pro)renin receptor (PRR) and renin. Intramedullary infusion of NaBu in Sprague-Dawley rats lowered the Ang II-induced mean arterial pressure from 129 ± 6 mmHg to 108 ± 4 mmHg (P renal injury, including urinary albumin, glomerulosclerosis, and renal fibrosis, as well as the expression of inflammatory mediators tumor necrosis factor α, interleukin 6. The renal expression of PRR, angiotensinogen, angiotensin I-converting enzyme and the urinary excretion of soluble PRR, renin, and angiotensinogen were all increased by Ang II infusion but decreased by NaBu treatment. In cultured innermedullary collecting duct cells, NaBu treatment attenuated Ang II-induced expression of PRR and renin. These results demonstrate that NaBu exerts an antihypertensive action, likely by suppressing the PRR-mediated intrarenal renin-angiotensin system.

  13. Regulation of renin secretion by renal juxtaglomerular cells

    DEFF Research Database (Denmark)

    Friis, Ulla G; Madsen, Kirsten; Stubbe, Jane

    2013-01-01

    A major rate-limiting step in the renin-angiotensin-aldosterone system is the release of active renin from endocrine cells (juxtaglomerular (JG) cells) in the media layer of the afferent glomerular arterioles. The number and distribution of JG cells vary with age and the physiological level...

  14. Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction

    DEFF Research Database (Denmark)

    Solomon, Scott D; Shin, Sung Hee; Shah, Amil

    2011-01-01

    Direct renin inhibitors provide an alternative approach to inhibiting the renin-angiotensin-aldosterone system (RAAS) at the most proximal, specific, and rate-limiting step. We tested the hypothesis that direct renin inhibition would attenuate left ventricular remodelling in patients following...

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

    Science.gov (United States)

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

    2011-08-01

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

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

    NARCIS (Netherlands)

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

    1997-01-01

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

  17. Oxygen sensitivity of potassium- and angiotensin II-stimulated aldosterone release by bovine adrenal cells.

    Science.gov (United States)

    Brickner, R C; Raff, H

    1991-04-01

    Angiotensin II (AII) and extracellular K+, acting through different intracellular mechanisms, stimulate aldosterone release in a synergistic fashion. We have previously shown that decreases in oxygen (O2) within the physiological range inhibit AII, cyclic AMP (cAMP) and ACTH-stimulated aldosterone release. The present experiment evaluated the effect of various concentrations of O2 on K+-stimulated aldosterone release in the presence and absence of AII. Dispersed bovine adrenal glomerulosa cells were incubated with different concentrations of K+ (0.9-5.4 mmol/l) without and with AII (10 nmol/l) under different concentrations of O2 (0, 5 or 50%); 21% O2 (pO2 = 19.9 +/- 0.5 kPa,n = 9) was used as reference control for comparison. In all cases, increases in K+ stimulated aldosterone release, an effect augmented by AII. Under 0% O2 (pO2 = 8.1 +/- 0.3 kPa, n = 3) and 5% O2 (pO2 = 12.8 +/- 0.5 kPa, n = 3), aldosterone release stimulated by K+ or K+/AII was significantly inhibited compared with that under 21% O2. Conversely, under 50% O2 (pO2 = 36.3 +/- 2.5 kPa, n = 3), aldosterone release stimulated by K+ or K+/AII was significantly augmented. Cortisol secretion was not significantly affected by 5% or 50% O2 but was significantly decreased under 0% O2. The effect of O2 on K+/AII stimulation of aldosterone release, as well as previous experiments with cAMP, progesterone and ACTH, suggest a final common post-receptor oxygen-sensitive component of the aldosterone synthetic pathway. It is suggested that one or more enzymes in the aldosterone synthetic pathway is/are exquisitely sensitive to small changes in O2 within the physiological range.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    . The importance of the RAS is clearly emphasised by the widespread use of drugs targeting this system in clinical practice. These include, renin inhibitors, angiotensin II receptor type I blockers, and inhibitors of the angiotensin converting enzyme. Some of the important effectors within the system are 7...... be important for receptor function, and in the development of cardiovascular diseases. This is very significant, since "dimers" may provide pharmacologists with novel targets for improved drug therapy. However, we know that 7TM receptors can mediate signals as monomeric units, and so far it has been very......The Renin-Angiotensin System (RAS) is important for the regulation of cardiovascular physiology, where it controls blood pressure, and salt- and water homeostasis. Dysregulation of RAS can lead to severe diseases including hypertension, diabetic nephropathy, and cardiac arrhythmia, and -failure...

  19. Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome

    Directory of Open Access Journals (Sweden)

    V Raghunathan

    2017-01-01

    Full Text Available Hypertension is common in hemolytic uremic syndrome (HUS and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency.

  20. 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 descri...

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

    Directory of Open Access Journals (Sweden)

    Fernanda S. Zamo

    2010-01-01

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

  2. Influence of Angiotensin-Aldosterone System on Ultrasound of Joints in Patients with Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    O.B. Komarova

    2014-02-01

    Full Text Available In patients with rheumatoid arthritis and high level of angiotensin II in the blood at ultrasound of joints there are often being detected effusion in the joint cavity, hypervascularization of synovium with 2–3 points and tenosynovitis characterizing inflammatory exudative processes. In patients with high level of aldosterone, hyperplasia of synovium, presence of pannus and bone and cartilage erosions, indicating proliferative-destructive processes, were predominated. Identified correlations show that with increasing levels of angiotensin II in the blood increases the intensity of the vascularization of the synovial membrane, joint effusion, and an increase in the concentration of aldosterone in the blood affects the synovial thickness indicators, the presence of pannus and bone erosions amount.

  3. Effect of deafferentation of the rat tongue on plasma corticosterone, aldosterone, angiotensin and ACTH levels

    International Nuclear Information System (INIS)

    Polyntsev, Yu.V.; Serova, O.N.

    1987-01-01

    The effect of deafferentation of the tongue on the plasma level of hormones involved in regulation of the sodium ion level -- aldosterone, corticosterone, ACTH, and angiotensin -- was studied. Plasma hormone levels were determined by radioimmunoassay. The results indicate the important role of orosensory and taste perception in the processes of regulation of the sodium balance in the body. The experiments in this study were conducted on rats

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    on mechanisms of postnatal development the renal medulla and putting medullary developmental lesions into perspective with regard to the programming effect. Moreover, the renin-angiotensin system is critically involved in mammalian kidney development and signaling disorders give rise to developmental renal...... disturbances reaching into adulthood. A review of current knowledge of the role of the renin-angiotensin system for renal medullary development will be given. Acta Physiologica © 2013 Scandinavian Physiological Society....... lesions that has been associated with hypertension later in life. A consistent finding in both experimental animal models and in human case reports is atrophy of the renal medulla with developmental lesions to both medullary nephron segments and vascular development with concomitant functional...

  5. Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism

    OpenAIRE

    KOBORI, HIROYUKI; ICHIHARA, ATSUHIRO; SUZUKI, HIROMICHI; TAKENAKA, TSUNEO; MIYASHITA, YUTAKA; HAYASHI, MATSUHIKO; SARUTA, TAKAO

    1997-01-01

    This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was onl...

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

    Directory of Open Access Journals (Sweden)

    Aline Cristina Piratello

    2010-01-01

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

  7. Exercise training modulates the hepatic renin-angiotensin system in fructose-fed rats.

    Science.gov (United States)

    Frantz, Eliete Dalla Corte; Medeiros, Renata Frauches; Giori, Isabele Gomes; Lima, Juliana Bittencourt Silveira; Bento-Bernardes, Thais; Gaique, Thaiane Gadioli; Fernandes-Santos, Caroline; Fernandes, Tiago; Oliveira, Edilamar Menezes; Vieira, Carla Paulo; Conte-Junior, Carlos Adam; Oliveira, Karen Jesus; Nobrega, Antonio Claudio Lucas

    2017-09-01

    What is the central question of this study? What are the effects of exercise training on the hepatic renin-angiotensin system and their contribution to damage resulting from fructose overload in rats? What is the main finding and its importance? Exercise training attenuated the deleterious actions of the angiotensin-converting enzyme/angiotensin II/angiotensin II type 1 receptor axis and increased expression of the counter-regulatory (angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor) axis in the liver. Therefore, our study provides evidence that exercise training modulates the hepatic renin-angiotensin system, which contributes to reducing the progression of metabolic dysfunction and non-alcoholic fatty liver disease in fructose-fed rats. The renin-angiotensin system (RAS) has been implicated in the development of metabolic syndrome. We investigated whether the hepatic RAS is modulated by exercise training and whether this modulation improves the deleterious effects of fructose overload in rats. Male Wistar rats were divided into (n = 8 each) control (CT), exercise control (CT-Ex), high-fructose (HFr) and exercise high-fructose (HFr-Ex) groups. Fructose-drinking rats received d-fructose (100 g l -1 ). After 2 weeks, CT-Ex and HFr-Ex rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min day -1 , 4 days per week). We assessed body mass, glucose and lipid metabolism, hepatic histopathology, angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity, the angiotensin concentration and the expression profile of proteins affecting the hepatic RAS, gluconeogenesis and inflammation. Neither fructose overload nor exercise training influenced body mass gain and serum ACE and ACE2 activity. The HFr group showed hyperinsulinaemia, but exercise training normalized this parameter. Exercise training was effective in preventing hepatic steatosis and in preventing triacylglycerol and

  8. 2C.07: INVOLVEMENT OF THE RENIN-ANGIOTENSIN SYSTEM IN A PREMATURE AGING MOUSE MODEL.

    Science.gov (United States)

    Van Thiel, B S; Ridwan, Y; Garrelds, I M; Vermeij, M; Groningen, M C Clahsen-Van; Danser, A H J; Essers, J; Van Der Pluijm, I

    2015-06-01

    Changes in the renin-angiotensin system (RAS), known for its critical role in the regulation of blood pressure and sodium homeostasis, may contribute to aging and age-related diseases. Here we characterized the RAS and kidney pathology in mice with genomic instability due to a defective nucleotide excision repair gene (Ercc1d/- mice). These mice display premature features of aging, including vascular dysfunction. Studies were performed in male and female Ercc1d/- mice and their wild type controls (Ercc1+/+) at the age of 12 or 18 weeks before and after treatment with losartan. The renin-activatable near-infrared fluorescent probe ReninSense 680™ was applied in vivo to allow non-invasive imaging of renin activity. Plasma renin concentrations (PRC) were additionally measured ex vivo by quantifying Ang I generation in the presence of excess angiotensinogen. Kidneys were harvested and examined for markers of aging, and albumin was determined in urine. Kidneys of 12-week old Ercc1d/- mice showed signs of aging, including tubular anisokaryosis, cell-senescence and increased apoptosis. This was even more pronounced at the age of 18 weeks. Yet, urinary albumin was normal at 12 weeks. The ReninSense 680™ probe showed increased intrarenal renin activity in Ercc1d/- mice versus Ercc1+/+ mice, both at 12 and 18 weeks of age, while PRC in these mice tended to be lower compared to Ercc1+/+ mice. Renin was higher in male than female mice, both in the kidney and in plasma, and losartan increased kidney and plasma renin in both Ercc1d/- and Ercc1+/+ mice. Rapidly aging Ercc1d/- mice display an activated intrarenal RAS, as evidenced by the increased fluorescence detected with the ReninSense 680™ probe. This increased RAS activity may contribute to the disturbed kidney pathology in these mice. The increased intrarenal activity detected with the ReninSense 680™ probe in male vs. female mice, as well as after losartan treatment, are in full agreement with the literature, and

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

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik

    2009-01-01

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

  10. Influence of antihypertensive therapy, sodium intake and the concentration of potassium in plasma on concentration of aldosterone and plasma renin activity

    Directory of Open Access Journals (Sweden)

    Lalić Tijana

    2013-01-01

    Full Text Available Introduction: Primary aldosteronism (PA is a group of disorders which are characterized by inadequate and non-suppressible production of aldosterone. The prevalence of PA is increasing in hypertensive population. The golden standard of screening for primary aldosteronism, determination of aldosterone/plasma renin activity (ARR, is influenced by numerous exogenous and endogenous factors. Testing cannot always be conducted under optimal conditions. Objective: To determine influence of antihypertensive drugs and concentrations of potassium and sodium in blood and urine on values of aldosterone and plasma renin activity. Methods: In this retrospective study, we analyzed medical reports of patients admitted to Department of thyroid gland disease in the period from 2009 to 2011, with increased risk for primary aldosteronism. Body weight and height, sodium and potassium in serum and urine, plasma aldosterone concentrations and plasma renin activity, data on medicines and comorbidity were analyzed in all patients. In processing data, statistical methods descriptive analysis, Student T test and univariate linear regression were applied. Result: Of 137 patients, there were more patients with resistant hypertension (53,28% than with adrenal tumors (46,72%. Most patients used calcium channel blockers. Treatment with alpha blockers and calcium channel blockers does not influence ARR. Beta blockers and ACE inhibitors can influence ARR and diuretics and vasodilatators have definite influence. Diabetes mellitus can have higher risk of false negative results. Urine sodium excretion is significantly correlated with plasma aldosteron and serum potassium. Plasma aldosteron and PRA are significantly correlated with concentrations of electrolites in urine. Conclusion: Increased prevalence of primary aldosteronism necessitates need for accurate and better diagnostics.

  11. Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

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    Indu Dhar

    Full Text Available The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs. Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs. HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH, proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.

  12. Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

    Science.gov (United States)

    Dhar, Indu; Dhar, Arti; Wu, Lingyun; Desai, Kaushik M

    2013-01-01

    The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs). Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories) for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs). HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH), proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE) and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.

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

    NARCIS (Netherlands)

    Mirkovic, K.; Frenay, A.S.; Born, J. van den; Goor, H van; Navis, G.; Borst, M.H. de; Bindels, R.J.M.; Hoenderop, J.G.J.; Hillebrands, J.L.

    2017-01-01

    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

  14. High-salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system.

    Science.gov (United States)

    Mao, Caiping; Liu, Rong; Bo, Le; Chen, Ningjing; Li, Shigang; Xia, Shuixiu; Chen, Jie; Li, Dawei; Zhang, Lubo; Xu, Zhice

    2013-07-01

    Intrauterine environments are related to fetal renal development and postnatal health. Influence of salty diets during pregnancy on renal functions and renin-angiotensin system (RAS) was determined in the ovine fetuses and offspring. Pregnant ewes were fed high-salt diet (HSD) or normal-salt diet (NSD) for 2 months during middle-to-late gestation. Fetal renal functions, plasma hormones, and mRNA and protein expressions of the key elements of renal RAS were measured in the fetuses and offspring. Fetal renal excretion of sodium was increased while urine volume decreased in the HSD group. Fetal blood urea nitrogen was increased, while kidney weight:body weight ratio decreased in the HSD group. The altered ratio was also observed in the offspring aged 15 and 90 days. Maternal and fetal plasma antidiuretic hormone was elevated without changes in plasma renin activity and Ang I levels, while plasma Ang II was decreased. The key elements of local renal RAS, including angiotensinogen, angiotensin converting enzyme (ACE), ACE2, AT1, and AT2 receptor expression in both mRNA and protein, except renin, were altered following maternal high salt intake. The results suggest that high intake of salt during pregnancy affected fetal renal development associated with an altered expression of the renal key elements of RAS, some alterations of fetal origins remained after birth as possible risks in developing renal or cardiovascular diseases.

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

    International Nuclear Information System (INIS)

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

    1976-01-01

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

  16. Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice.

    Science.gov (United States)

    Zhang, Y; Wang, L; Song, Y; Zhao, X; Wong, M S; Zhang, W

    2016-03-01

    The skeletal renin-angiotensin system contributes to the development of osteoporosis. The renin inhibitor aliskiren exhibited beneficial effects on trabecular bone of osteoporotic mice, and this action might be mediated through angiotensin and bradykinin receptor pathways. This study implies the potential application of renin inhibitor in the management for postmenopausal osteoporosis. The skeletal renin-angiotensin system plays key role in the pathological process of osteoporosis. The present study is designed to elucidate the effect of renin inhibitor aliskiren on trabecular bone and its potential action mechanism in ovariectomized (OVX) mice. The OVX mice were treated with low dose (5 mg/kg) or high dose (25 mg/kg) of aliskiren or its vehicle for 8 weeks. The bone turnover markers were measured by ELISA. The structural parameters of trabecular bone at lumbar vertebra (LV) and distal femoral metaphysis were measured by micro-CT. The expression of messenger RNA (mRNA) and protein was studied by RT-PCR and immunoblotting, respectively. Aliskiren treatment reduced urinary excretion of calcium and serum level of tartrate-resistant acid phosphatase in OVX mice. The treatment with aliskiren significantly increased bone volume (BV/TV) and connectivity density (Conn.D) of trabecular bone at LV-2 and LV-5 as well as dramatically enhanced BV/TV, Conn.D, bone mineral density (BMD/BV) and decreased bone surface (BS/BV) at the distal femoral end. Aliskiren significantly down-regulated the expression of angiotensinogen, angiotensin II (Ang II), Ang II type 1 receptor, bradykinin receptor (BR)-1, and osteocytic-specific gene sclerostin as well as the osteoclast-specific genes, including carbonic anhydrase II, matrix metalloproteinase-9, and cathepsin K. This study revealed that renin inhibitor aliskiren exhibited the beneficial effects on trabecular bone of ovariectomy-induced osteoporotic mice, and the underlying mechanism for this action might be mediated through Ang II and

  17. Some Aspects of the Renin-Angiotensin-System in Hemodialysis Patients

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    Umar Malik

    2015-11-01

    Full Text Available Understanding of the renin-angiotensin system (RAS has changed remarkably over the past decade. Renin, angiotensin converting enzyme (ACE, angiotensin II (Ang II, and Ang II receptors are the main components of the RAS. Recent studies identified the ACE2/Ang 1-7/Mas receptor axis, which counter-regulates the classical RAS. Many studies have examined the effects of the RAS on the progression of cardiovascular disease and chronic kidney disease (CKD. In addition, many studies have documented increased levels of ACE in hemodialysis (HD patients, raising concerns about the negative effects of RAS activation on the progression of renal disease. Elevated ACE increases the level of Ang II, leading to vasoconstriction and cell proliferation. Ang II stimulation of the sympathetic system leads to renal and cardiovascular complications that are secondary to uncontrolled hypertension. This review provides an overview of the RAS, evaluates new research on the role of ACE2 in dialysis, and reviews the evidence for potentially better treatments for patients undergoing HD. Further understanding of the role of ACE and ACE2 in HD patients may aid the development of targeted therapies that slow the progression of CKD and cardiovascular disease.

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

    OpenAIRE

    Renna, N. F.; Lembo, C.; Diez, E.; Miatello, R. M.

    2013-01-01

    (1) is study aims to demonstrate the causal involvement of renin angiotensin system (RAS) and oxidative stress (OS) on vascular inammation in an experimental model of metabolic syndrome (MS) achieved by fructose administration to spontaneously hypertensive rats (FFHR) during 12 weeks. (2) Chronic treatment with candesartan (C) (10 mg/kg per day for the last 6 weeks) or 4OH-Tempol (T) (10−3 mmol/L in drinking water for the last 6 weeks) reversed the increment in metabolic variables and systo...

  19. Relative Atrial Natriuretic Peptide Deficiency and Inadequate Renin and Angiotensin II Suppression in Obese Hypertensive Men

    DEFF Research Database (Denmark)

    Asferg, Camilla L; Nielsen, Søren J; Andersen, Ulrik B

    2013-01-01

    Obesity is a strong risk factor for hypertension, but the mechanisms by which obesity leads to hypertension are incompletely understood. On this background, we assessed dietary sodium intake, serum levels of natriuretic peptides (NPs), and the activity of the renin-angiotensin system in 63 obese...... hypertensive men (obeseHT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure, ≥130/80 mm Hg), in 40 obese normotensive men (obeseNT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure,...

  20. Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cochrane Review)

    DEFF Research Database (Denmark)

    Graudal, Niels A; Hubeck-Graudal, Thorbjørn; Jürgens, Gesche

    2012-01-01

    The question of whether reduced sodium intake is effective as a health prophylaxis initiative is unsolved. The purpose was to estimate the effects of low-sodium vs. high-sodium intake on blood pressure (BP), renin, aldosterone, catecholamines, and lipids....

  1. Expression of the Components of the Renin-Angiotensin System in Venous Malformation

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    Sam eSiljee

    2016-05-01

    Full Text Available Background Venous malformation (VM is the most common form of vascular malformation, consisting of a network of thin-walled ectatic venous channels with deficient or absent media. This study investigated the expression of the components of the renin-angiotensin system (RAS, namely (prorenin receptor (PRR, angiotensin converting enzyme (ACE, angiotensin II receptor 1 (ATIIR1 and angiotensin II receptor 2 (AIITR2 in subcutaneous (SC and intramuscular (IM VM. Materials and Methods SC (n=7 and IM (n=7 VM were analyzed for the expression of PRR, ACE, ATIIR1, and ATIIR2 using 3,3-diaminobenzidine (DAB and immunofluorescent (IF immunohistochemical (IHC staining and NanoString gene expression analysis. Results IHC staining showed expression of PRR, ACE, ATIIR1 and faint expression of ATIIR2 in the endothelium of SC and IM VM. Furthermore, ATIIR2 was expressed by cells away from the endothelium in both SC and IM VM lesions examined. NanoString analysis demonstrated the presence of PRR, ACE and ATIIR1 but not ATIIR2.Conclusions The presence of PRR, ACE, ATIIR1 and potentially ATIIR2, in both SC and IM VM suggests a role for the RAS in the biology of VM. This novel finding may lead to a mechanism-based therapy for VM.

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

    Science.gov (United States)

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

    2015-05-01

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

  3. The role of local renin-angiotensin system in arterial chemoreceptors in sleep-breathing disorders

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    Man Lung eFung

    2014-09-01

    Full Text Available The renin-angiotensin system (RAS plays pivotal roles in the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Experimental studies have demonstrated a locally expressed RAS in the carotid body, which is functional significant in the effect of angiotensin peptides on the regulation of the activity of peripheral chemoreceptors and the chemoreflex. The physiological and pathophysiological implications of the RAS in the carotid body have been proposed upon recent studies showing a significant upregulation of the RAS expression under hypoxic conditions relevant to altitude acclimation and sleep apnea and also in animal model of heart failure. Specifically, the increased expression of angiotensinogen, angiotensin-converting enzyme and angiotensin AT1 receptors plays significant roles in the augmented carotid chemoreceptor activity and inflammation of the carotid body. This review aims to summarize these results with highlights on the pathophysiological function of the RAS under hypoxic conditions. It is concluded that the maladaptive changes of the RAS in the carotid body plays a pathogenic role in sleep apnea and heart failure, which could potentially be a therapeutic target for the treatment of the pathophysiological consequence of sleep apnea.

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

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U.; Dhamrait, S.S.; Sethi, A.A.

    2008-01-01

    BACKGROUND: The deletion-allele of the angiotensin-converting enzyme (ACE) gene and elevated ACE activity are associated with increased risk of severe hypoglycemia in type 1 diabetes. We explored whether genetic and phenotypic variations in other components of the renin-angiotensin system...... are similarly associated. METHODS: Episodes of severe hypoglycemia were recorded in 171 consecutive type 1 diabetic outpatients during a 1-year follow-up. Participants were characterized at baseline by gene polymorphisms in angiotensinogen, ACE, angiotensin-II receptor types 1 (AT1R) and 2 (AT2R), and by plasma...... associate with high risk of severe hypoglycemia in type 1 diabetes. A potential preventive effect of renin-angiotensin system blocking drugs in patients with recurrent severe hypoglycemia merits further investigation Udgivelsesdato: 2008/3...

  5. Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog.

    Science.gov (United States)

    Anderson, W P; Johnston, C I; Korner, P I

    1979-01-01

    1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance. PMID:219182

  6. Role of proteinuria in the regulation of renal renin-angiotensin system components in unilateral proteinuric rats

    NARCIS (Netherlands)

    Deelman, LE; Navis, G; Wietses, M; de Zeeuw, D; Henning, RH

    Renin-angiotensin system (RAS) overactivity has been implied in progressive renal function loss. We investigated whether changes in the renal expression of RAS components are specifically associated with the proteinuric kidney. Unilateral adriamycin-induced proteinuria was obtained by clamping the

  7. Severe hypoglycaemia during pregnancy in women with type 1 diabetes: possible role of renin-angiotensin system activity?

    DEFF Research Database (Denmark)

    Nielsen, L Ringholm; Pedersen-Bjergaard, U; Thorsteinsson, B

    2009-01-01

    AIMS: To investigate whether increased risk of severe hypoglycaemia in early pregnancy is related to pregnancy-induced changes in renin-angiotensin system (RAS) activity in women with type 1 diabetes (T1DM). METHODS: Severe hypoglycaemic events the year preceding pregnancy were recorded...... retrospectively in 107 consecutive pregnant women with T1DM. Events during pregnancy were recorded prospectively. Measurements of ACE, renin and angiotensinogen were determined at 8, 14, 21, 27 and 33 weeks and postpartum. RESULTS: The rate of severe hypoglycaemia was 1.1 and 5.3 events/patient-year the year...... preceding pregnancy and postpartum ACE activity (relative rate of severe hypoglycaemia above versus below median ACE activity: 4.4 (CI: 1.7-11.9), p=0.003). No association was found between severe hypoglycaemia during pregnancy and renin angiotensin system activity at 8 weeks. CONCLUSIONS: In early...

  8. Brain Renin-Angiotensin System and Microglial Polarization: Implications for Aging and Neurodegeneration

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    Jose L. Labandeira-Garcia

    2017-05-01

    Full Text Available Microglia can transform into proinflammatory/classically activated (M1 or anti-inflammatory/alternatively activated (M2 phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory to M2 (immunoregulatory phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS on microglial polarization are less known. It is well known that there is a “classical” circulating RAS; however, a second RAS (local or tissue RAS has been observed in many tissues, including brain. The locally formed angiotensin is involved in local pathological changes of these tissues and modulates immune cells, which are equipped with all the components of the RAS. There are also recent data showing that brain RAS plays a major role in microglial polarization. Level of microglial NADPH-oxidase (Nox activation is a major regulator of the shift between M1/proinflammatory and M2/immunoregulatory microglial phenotypes so that Nox activation promotes the proinflammatory and inhibits the immunoregulatory phenotype. Angiotensin II (Ang II, via its type 1 receptor (AT1, is a major activator of the NADPH-oxidase complex, leading to pro-oxidative and pro-inflammatory effects. However, these effects are counteracted by a RAS opposite arm constituted by Angiotensin II/AT2 receptor signaling and Angiotensin 1–7/Mas receptor (MasR signaling. In addition, activation of prorenin-renin receptors may contribute to activation of the proinflammatory phenotype. Aged brains showed upregulation of AT1 and downregulation of AT2 receptor expression, which may contribute to a pro-oxidative pro-inflammatory state and the increase in neuron vulnerability. Several recent studies have shown interactions between the brain RAS and different factors involved in microglial polarization

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

    Directory of Open Access Journals (Sweden)

    Madhu Nath

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

  10. Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their Expression

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    Shane D. Sykes

    2015-01-01

    Full Text Available The intrauterine renin angiotensin system (RAS is implicated in placentation and labour onset. Here we investigate whether promoter methylation of RAS genes changes with gestation or labour and if it affects gene expression. Early gestation amnion and placenta were studied, as were term amnion, decidua, and placenta collected before labour (at elective caesarean section or after spontaneous labour and delivery. The expression and degree of methylation of the prorenin receptor (ATP6AP2, angiotensin converting enzyme (ACE, angiotensin II type 1 receptor (AGTR1, and two proteases that can activate prorenin (kallikrein, KLK1, and cathepsin D, CTSD were measured by qPCR and a DNA methylation array. There was no effect of gestation or labour on the methylation of RAS genes and CTSD. Amnion and decidua displayed strong correlations between the percent hypermethylation of RAS genes and CTSD, suggestive of global methylation. There were no correlations between the degree of methylation and mRNA abundance of any genes studied. KLK1 was the most methylated gene and the proportion of hypermethylated KLK1 alleles was lower in placenta than decidua. The presence of intermediate methylated alleles of KLK1 in early gestation placenta and in amnion after labour suggests that KLK1 methylation is uniquely dynamic in these tissues.

  11. Tissue Renin-Angiotensin Systems: A Unifying Hypothesis of Metabolic Disease

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    Jeppe eSkov

    2014-02-01

    Full Text Available The actions of angiotensin peptides are diverse and locally acting tissue renin-angiotensin systems (RAS are present in almost all tissues of the body. An activated RAS strongly correlates to metabolic disease (e.g. diabetes and its complications and blockers of RAS have been demonstrated to prevent diabetes in humans.Hyperglycemia, obesity, hypertension, and cortisol are well-known risk factors of metabolic disease and all stimulate tissue RAS whereas glucagon-like peptide-1, vitamin D, and aerobic exercise are inhibitors of tissue RAS and to some extent can prevent metabolic disease. Furthermore, an activated tissue RAS deteriorates the same risk factors creating a system with several positive feedback pathways. The primary effector hormone of the RAS, angiotensin II, stimulates reactive oxygen species, induces tissue damage, and can be associated to most diabetic complications. Based on these observations we hypothesize that an activated tissue RAS is the principle cause of metabolic syndrome and type 2 diabetes, and additionally is mediating the majority of the metabolic complications. The involvement of positive feedback pathways may create a self-reinforcing state and explain why metabolic disease initiate and progress. The hypothesis plausibly unify the major predictors of metabolic disease and places tissue RAS regulation in the center of metabolic control.

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

    Science.gov (United States)

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

    2017-01-01

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

  13. Renin-Angiotensin System Blockade Improves Cardiac Indices in Acromegaly Patients.

    Science.gov (United States)

    Thomas, Julia D J; Dattani, Abhishek; Zemrak, Filip; Burchell, Thomas; Akker, Scott A; Kaplan, Felicity J L; Khoo, Bernard; Aylwin, Simon; Grossman, Ashley B; Davies, L Ceri; Korbonits, Márta

    2017-06-01

    Blockade of the angiotensin-renin system, with angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), has been shown to improve cardiac outcomes following myocardial infarction and delay progression of heart failure. Acromegaly is associated with a disease-specific cardiomyopathy, the pathogenesis of which is poorly understood.The cardiac indices of patients with active acromegaly with no hypertension (Group A, n=4), established hypertension not taking ACEi/ARBs (Group B, n=4) and established hypertension taking ACEi/ARBs (Group C, n=4) were compared using cardiac magnetic imaging.Patients taking ACEi/ARBs had lower end diastolic volume index (EDVi) and end systolic volume index (ESVi) than the other 2 groups ([C] 73.24 vs. [A] 97.92 vs. [B] 101.03 ml/m 2 , ANOVA p=0.034, B vs. C pAcromegaly patients on ACEi/ARBs for hypertension demonstrate improved cardiac indices compared to acromegaly patients with hypertension not taking these medications. Further studies are needed to determine if these drugs have a beneficial cardiac effect in acromegaly in the absence of demonstrable hypertension. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Gene expression profiling following maternal deprivation: Involvement of the brain renin-angiotensin system

    Directory of Open Access Journals (Sweden)

    Claudia Liebl

    2009-05-01

    Full Text Available The postnatal development of the mouse is characterized by a stress hyporesponsive period (SHRP, where basal corticosterone levels are low and responsiveness to mild stressors is reduced. Maternal separation is able to disrupt the SHRP and is widely used to model early trauma. In this study we aimed at identifying of brain systems involved in acute and possible long-term effects of maternal separation. We conducted a microarray-based gene expression analysis in the hypothalamic paraventricular nucleus after maternal separation, which revealed 52 differentially regulated genes compared to undisturbed controls, among them are 37 up-regulated and 15 down-regulated genes. One of the prominently up-regulated genes, angiotensinogen, was validated using in-situ hybridization. Angiotensinogen is the precursor of angiotensin II, the main effector of the brain renin-angiotensin system (RAS, which is known to be involved in stress system modulation in adult animals. Using the selective angiotensin type I receptor (AT(1 antagonist candesartan we found strong effects on CRH and GR mRNA expression in the brain a nd ACTH release following maternal separation. AT(1 receptor blockade appears to enhance central effects of maternal separation in the neonate, suggesting a suppressing function of brain RAS during the SHRP. Taken together, our results illustrate the molecular adaptations that occur in the paraventricular nucleus following maternal separation and contribute to identifying signaling cascades that control stress system activity in the neonate.

  15. Autonomic, locomotor and cardiac abnormalities in a mouse model of muscular dystrophy: targeting the renin-angiotensin system.

    Science.gov (United States)

    Sabharwal, Rasna; Chapleau, Mark W

    2014-04-01

    New Findings What is the topic of this review? This symposium report summarizes autonomic, cardiac and skeletal muscle abnormalities in sarcoglycan-δ-deficient mice (Sgcd-/-), a mouse model of limb girdle muscular dystrophy, with emphasis on the roles of autonomic dysregulation and activation of the renin-angiotensin system at a young age. What advances does it highlight? The contributions of the autonomic nervous system and the renin-angiotensin system to the pathogenesis of muscular dystrophy are highlighted. Results demonstrate that autonomic dysregulation precedes and predicts later development of cardiac dysfunction in Sgcd-/- mice and that treatment of young Sgcd-/- mice with the angiotensin type 1 receptor antagonist losartan or with angiotensin-(1-7) abrogates the autonomic dysregulation, attenuates skeletal muscle pathology and increases spontaneous locomotor activity. Muscular dystrophies are a heterogeneous group of genetic muscle diseases characterized by muscle weakness and atrophy. Mutations in sarcoglycans and other subunits of the dystrophin-glycoprotein complex cause muscular dystrophy and dilated cardiomyopathy in animals and humans. Aberrant autonomic signalling is recognized in a variety of neuromuscular disorders. We hypothesized that activation of the renin-angiotensin system contributes to skeletal muscle and autonomic dysfunction in mice deficient in the sarcoglycan-δ (Sgcd) gene at a young age and that this early autonomic dysfunction contributes to the later development of left ventricular (LV) dysfunction and increased mortality. We demonstrated that young Sgcd-/- mice exhibit histopathological features of skeletal muscle dystrophy, decreased locomotor activity and severe autonomic dysregulation, but normal LV function. Autonomic regulation continued to deteriorate in Sgcd-/- mice with age and was accompanied by LV dysfunction and dilated cardiomyopathy at older ages. Autonomic dysregulation at a young age predicted later development of

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

    Science.gov (United States)

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

    2017-12-27

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

  17. Association between polymorphisms in renin-angiotensin system genes and primary ovarian insufficiency in Korean women.

    Science.gov (United States)

    Jung, Yong Wook; Jeon, Young Joo; Park, Hye Mi; Lee, Bo Eun; Rah, Hyungchul; Lee, Woo Sik; Yoon, Tae Ki; Kim, Nam Keun

    2013-05-01

    The purpose of this study was to evaluate the relationship between angiotensin-converting enzyme (ACE; insertion/deletion), angiotensinogen (AGT M235T), and angiotensin II type 1 receptor (AT1R 1166A>C) and the prevalence of primary ovarian insufficiency (POI) in Korean women. A total of 133 women with POI and 238 controls were genotyped for polymorphic sites in each gene using polymerase chain reaction-restriction fragment length polymorphism analysis. ACE ID and ID + II variants occurred more frequently in women with POI than in controls (odds ratio [OR], 1.830; 95% CI, 1.040-3.221; P = 0.040; and OR, 1.797; 95% CI, 1.055-3.060; P = 0.031, respectively). The AT1R 1166AC genotype occurred more frequently in participants with POI than in controls (OR, 3.171; 95% CI, 1.562-6.436; P = 0.002). Comparing the combined genotype frequencies of ACE/AT1R revealed that the frequencies of ID/AA, ID/AC, and II/AC were higher in participants than in controls (OR, 1.916; 95% CI, 1.053-3.485; P = 0.043; OR, 3.544; 95% CI, 1.207-10.407; P = 0.036; and OR, 7.875; 95% CI, 2.224-27.881; P = 0.001, respectively). The TT/AC genotype for combined genotyping of AGT/AT1R was more frequently observed in the POI group than in the control group (OR, 3.472; 95% CI, 1.450-8.313; P = 0.006). In multifactor dimensionality reduction-based haplotype analysis, the I-T-C genotype of ACE/AGT/AT1R was a possible predisposing factor for POI (OR, 4.678; 95% CI, 1.721-12.717; P = 0.002). This study demonstrates that polymorphisms in the renin-angiotensin system are related to the prevalence of POI. Thus, these renin-angiotensin system genes may serve as a novel marker for predicting the development of POI.

  18. Plasma aldosterone concentrations and plasma renin activity in healthy dogs and dogs with hyperadrenocorticism

    NARCIS (Netherlands)

    Javadi, S; Mol, JA; Boer, P; Boer, WH; Runberk, A

    2003-01-01

    The mean (se) basal plasma aldosterone concentrations were significantly lower in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH) (75 [9] pmol/litre) than in 12 healthy dogs (118 [14] pmol/litre), whereas in five dogs with hyperadrenocorticism due to an adrenocortical tumour they were

  19. A potential pathophysiological role for galectins and the renin-angiotensin system in preeclampsia.

    Science.gov (United States)

    Blois, Sandra M; Dechend, Ralf; Barrientos, Gabriela; Staff, Anne Cathrine

    2015-01-01

    This review discusses a potential role of galectins and the renin-angiotensin system (RAS) in the pathophysiology of preeclampsia (PE). Preeclampsia affects between 3 and 5 % of all pregnancies and is a heterogeneous disease, which may be caused by multiple factors. The only cure is the delivery of the placenta, which may result in a premature delivery and baby. Probably due to its heterogeneity, PE studies in human have hitherto only led to the identification of a limited number of factors involved in the pathogenesis of the disease. Animal models, particularly in mice and rats, have been used to gain further insight into the molecular pathology behind PE. In this review, we discuss the picture emerging from human and animal studies pointing to galectins and the RAS being associated with the PE syndrome and affecting a broad range of cellular signaling components. Moreover, we review the epidemiological evidence for PE increasing the risk of future cardiovascular disease later in life.

  20. Role of the inhibitors of angiotensin renin system on the DNA integrity of irradiated spermatozoids

    International Nuclear Information System (INIS)

    Spadella, Maria A.; Mansano, Naira S.; Schwarz, Franciele C.; Viani, Gustavo A.; Chies, Agnaldo B.

    2016-01-01

    Radiation action in the testes can significantly affect the reproductive capacity due to oxidative stress generated; phenomenon in which there is evidence of involvement of the Renin Angiotensin System (RAS). This study evaluated the role of AT1 receptor inhibitors, in mitigating the radioinduced DNA damage sperm from semen samples left vas deferens. Male Wistar rats were divided into six experimental groups: Control, 5Gy, Telmisartan (12mg/kg/day) and Losartan (34mg/kg/2x/day), 5 Gy + Telmisartan and 5 Gy + Losartan. The results showed increase in the percentage of sperm with fragmented DNA in irradiated groups when compared to controls, which was not reversed in the irradiated and treated groups. The radiation of 5Gy (single dose) affected the DNA-protein complex of the sperm and the treatments did not influence in reversing this damage, considering the experimental protocol used. (author)

  1. Dysregulation of Aldosterone Secretion in Mast Cell-Deficient Mice.

    Science.gov (United States)

    Boyer, Hadrien-Gaël; Wils, Julien; Renouf, Sylvie; Arabo, Arnaud; Duparc, Céline; Boutelet, Isabelle; Lefebvre, Hervé; Louiset, Estelle

    2017-12-01

    Resident adrenal mast cells have been shown to activate aldosterone secretion in rat and man. Especially, mast cell proliferation has been observed in adrenal tissues from patients with aldosterone-producing adrenocortical adenoma. In the present study, we show that the activity of adrenal mast cells is stimulated by low-sodium diet and correlates with aldosterone synthesis in C57BL/6 and BALB/c mice. We have also investigated the regulation of aldosterone secretion in mast cell-deficient C57BL/6 Kit W-sh/W-sh mice in comparison with wild-type C57BL/6 mice. Kit W-sh/W-sh mice submitted to normal sodium diet had basal plasma aldosterone levels similar to those observed in wild-type animals. Conversely, low-sodium diet unexpectedly induced an exaggerated aldosterone response, which seemed to result from an increase in adrenal renin and angiotensin type 1 receptor expression. Severe hyperaldosteronism was associated with an increase in systolic blood pressure and marked hypokalemia, which favored polyuria. Adrenal renin and angiotensin type 1 receptor overexpression may represent a compensatory mechanism aimed at activating aldosterone production in the absence of mast cells. Finally, C57BL/6 Kit W-sh/W-sh mice represent an unexpected animal model of primary aldosteronism, which has the particularity to be triggered by sodium restriction. © 2017 American Heart Association, Inc.

  2. Renin angiotensin system blockage associates with insertion/deletion polymorphism of angiotensin-converting enzyme in patients with hypertensive emergency.

    Science.gov (United States)

    Vilela-Martin, José F; Vaz-de-Melo, Renan O; Cosenso-Martin, Luciana N; Kuniyoshi, Cristina H; Yugar-Toledo, Juan C; Pinhel, Marcela A S; de Souza, Gisele F; Souza, Dorotéia R S; Pimenta, Eduardo; Moreno, Heitor; Cipullo, José P

    2013-09-01

    Hypertensive crisis (HC) stands out as a form of acute elevation of blood pressure (BP). It can manifest itself as hypertensive emergency (HE) or hypertensive urgency (HU), which is usually accompanied with levels of diastolic BP ≥120 mmHg. Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism may influence manifestations of HC. Thus, this study evaluated the influence of ACE I/D polymorphism in individuals with HC. A total of 187 patients admitted with HC (HU [n=69] and HE [n=118]) and 75 normotensive individuals were included in the study. Peripheral blood was drawn for a biochemical and genetic analysis of the ACE I/D polymorphism by Polymerase Chain Reaction. HC group showed higher systolic BP, body mass index (BMI), glycemia, creatinine, and lower high-density lipoprotein (HDL) cholesterol compared with normotensive individuals. The use of renin-angiotensin system (RAS) blockers was more frequent in the HU group than in the HE group (p=0.020). The II genotype was more predominant in normotensive and HU individuals than among HE individuals (18.7%, 11.6%, and 2.5%, respectively; p=0.004). Higher BMI and glycemia were associated with HC in the logistic regression model. ACE II genotype (odds ratio [OR] 0.14; 95% confidence interval [CI] 0.04-0.51) and HDL cholesterol were protective for the development of HE. ACE II genotype was present in the HU group, compared with the HE group (OR 0.18; 95% CI 0.04-0.88). This study shows an association between the low prevalence of ACE I/D polymorphism II genotype and a greater occurrence of HE in Brazilian individuals. The lower blockage of RAS, which was detected in the HE group, may interact with the low frequency of II genotype, conferring an increased risk for HE.

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

    Czech Academy of Sciences Publication Activity Database

    Kurtz, T. W.; Pravenec, Michal

    2004-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    This study investigated renin-angiotensin system (RAS)-induced cardiac remodeling and its reversibility in the presence and absence of high blood pressure (BP) in Cyp1a1-Ren2 transgenic inducible hypertensive rats (IHR). In IHR (pro)renin levels and BP can be dose-dependently titrated by oral...... administration of indole-3-carbinol (I3C). Young (four-weeks old) and adult (30-weeks old) IHR were fed I3C for four weeks (leading to systolic BP >200 mmHg). RAS-stimulation was stopped and animals were followed-up for a consecutive period. Cardiac function and geometry was determined echocardiographically...

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

    Science.gov (United States)

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

    2015-06-11

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

  6. Role of the intrarenal renin-angiotensin system in the progression of renal disease.

    Science.gov (United States)

    Urushihara, Maki; Kagami, Shoji

    2017-09-01

    The intrarenal renin-angiotensin system (RAS) has many well-documented pathophysiologic functions in both blood pressure regulation and renal disease development. Angiotensin II (Ang II) is the major bioactive product of the RAS. It induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation. In addition, Ang II regulates the gene expression of bioactive substances and activates multiple intracellular signaling pathways that are involved in renal damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, intracellular formation of reactive oxygen species, cell proliferation, and extracellular matrix synthesis, which in turn facilities renal injury. Involvement of angiotensinogen (AGT) in intrarenal RAS activation and development of renal disease has previously been reported. Moreover, studies have demonstrated that the urinary excretion rates of AGT provide a specific index of the intrarenal RAS status. Enhanced intrarenal AGT levels have been observed in experimental models of renal disease, supporting the concept that AGT plays an important role in the development and progression of renal disease. In this review, we focus on the role of intrarenal RAS activation in the pathophysiology of renal disease. Additionally, we explored the potential of urinary AGT as a novel biomarker of intrarenal RAS status in renal disease.

  7. Oxidative Stress/Angiotensinogen/Renin-Angiotensin System Axis in Patients with Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Masumi Kamiyama

    2013-11-01

    Full Text Available Although recent studies have proven that renin-angiotensin system (RAS blockades retard the progression of diabetic nephropathy, the detailed mechanisms of their reno-protective effects on the development of diabetic nephropathy remain uncertain. In rodent models, it has been reported that reactive oxygen species (ROS are important for intrarenal angiotensinogen (AGT augmentation in the progression of diabetic nephropathy. However, no direct evidence is available to demonstrate that AGT expression is enhanced in the kidneys of patients with diabetes. To examine whether the expression levels of ROS- and RAS-related factors in kidneys are increased with the progression of diabetic nephropathy, biopsied samples from 8 controls and 27 patients with type 2 diabetes were used. After the biopsy, these patients were diagnosed with minor glomerular abnormality or diabetes mellitus by clinical and pathological findings. The intensities of AGT, angiotensin II (Ang II, 4-hydroxy-2-nonenal (4-HNE, and heme oxygenase-1 (HO-1 were examined by fluorescence in situ hybridization and/or immunohistochemistry. Expression levels were greater in patients with diabetes than in control subjects. Moreover, the augmented intrarenal AGT mRNA expression paralleled renal dysfunction in patients with diabetes. These data suggest the importance of the activated oxidative stress/AGT/RAS axis in the pathogenesis of diabetic nephropathy.

  8. Skeletal muscle wasting: new role of nonclassical renin-angiotensin system.

    Science.gov (United States)

    Cabello-Verrugio, Claudio; Rivera, Juan C; Garcia, Dominga

    2017-05-01

    Skeletal muscle can be affected by many physiological and pathological conditions that contribute to the development of muscle weakness, including skeletal muscle loss, inflammatory processes, or fibrosis. Therefore, research into therapeutic treatment alternatives or alleviation of these effects on skeletal muscle is of great importance. Recent studies have shown that angiotensin (1-7) [Ang-(1-7)] - a vasoactive peptide of the nonclassical axis in the renin-angiotensin system (RAS) - and its Mas receptor are expressed in skeletal muscle. Ang-(1-7), through its Mas receptor, prevents or diminishes deleterious effects induced by skeletal muscle disease or injury. Specifically, the Ang-(1-7)-Mas receptor axis modulates molecular mechanisms involved in muscle mass regulation, such as the ubiquitin proteasome pathway, the insulin-like growth factor type 1/Akt (protein kinase B) pathway, or myonuclear apoptosis, and also inflammation and fibrosis pathways. Although further research into this topic and the possible side effects of Ang-(1-7) is necessary, these findings are promising, and suggest that the Ang-(1-7)-Mas axis can be considered a possible therapeutic target for treating patients with muscular disorders.

  9. Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer.

    Science.gov (United States)

    Blute, Michael L; Rushmer, Timothy J; Shi, Fangfang; Fuller, Benjamin J; Abel, E Jason; Jarrard, David F; Downs, Tracy M

    2015-11-01

    Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer. Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival. Median patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in

  10. Hypertrophic response to hemodynamic overload: role of load vs. renin-angiotensin system activation

    Science.gov (United States)

    Koide, M.; Carabello, B. A.; Conrad, C. C.; Buckley, J. M.; DeFreyte, G.; Barnes, M.; Tomanek, R. J.; Wei, C. C.; Dell'Italia, L. J.; Cooper, G. 4th; hide

    1999-01-01

    Myocardial hypertrophy is one of the basic mechanisms by which the heart compensates for hemodynamic overload. The mechanisms by which hemodynamic overload is transduced by the cardiac muscle cell and translated into cardiac hypertrophy are not completely understood. Candidates include activation of the renin-angiotensin system (RAS) and angiotensin II receptor (AT1) stimulation. In this study, we tested the hypothesis that load, independent of the RAS, is sufficient to stimulate cardiac growth. Four groups of cats were studied: 14 normal controls, 20 pulmonary artery-banded (PAB) cats, 7 PAB cats in whom the AT1 was concomitantly and continuously blocked with losartan, and 8 PAB cats in whom the angiotensin-converting enzyme (ACE) was concomitantly and continuously blocked with captopril. Losartan cats had at least a one-log order increase in the ED50 of the blood pressure response to angiotensin II infusion. Right ventricular (RV) hypertrophy was assessed using the RV mass-to-body weight ratio and ventricular cardiocyte size. RV hemodynamic overload was assessed by measuring RV systolic and diastolic pressures. Neither the extent of RV pressure overload nor RV hypertrophy that resulted from PAB was affected by AT1 blockade with losartan or ACE inhibition with captopril. RV systolic pressure was increased from 21 +/- 3 mmHg in normals to 68 +/- 4 mmHg in PAB, 65 +/- 5 mmHg in PAB plus losartan and 62 +/- 3 mmHg in PAB plus captopril. RV-to-body weight ratio increased from 0.52 +/- 0.04 g/kg in normals to 1.11 +/- 0.06 g/kg in PAB, 1.06 +/- 0.06 g/kg in PAB plus losartan and 1.06 +/- 0.06 g/kg in PAB plus captopril. Thus 1) pharmacological modulation of the RAS with losartan and captopril did not change the extent of the hemodynamic overload or the hypertrophic response induced by PAB; 2) neither RAS activation nor angiotensin II receptor stimulation is an obligatory and necessary component of the signaling pathway that acts as an intermediary coupling load to the

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

    Science.gov (United States)

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

    2018-04-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

  13. Changes in the renin angiotensin system during the development of colorectal cancer liver metastases

    International Nuclear Information System (INIS)

    Neo, Jaclyn H; Ager, Eleanor I; Angus, Peter W; Zhu, Jin; Herath, Chandana B; Christophi, Christopher

    2010-01-01

    Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease. Immunohistochemistry and quantitative RT-PCR was used to examine RAS expression in a mouse CRC liver metastases model. CRC metastases and liver tissue was assessed separately at key stages of CRC liver metastases development in untreated (control) mice and in mice treated with the ACE inhibitor captopril (750 mg/kg/day). Non-tumor induced (sham) mice indicated the effect of tumors on normal liver RAS. The statistical significance of multiple comparisons was determined using one-way analysis of variance followed by Bonferroni adjustment with SAS/STAT software. Reduced volume of CRC liver metastases with captopril treatment was evident. Local RAS of CRC metastases differed from the surrounding liver, with lower angiotensin II type 1 receptor (AT1R) expression but increased ANG-(1-7) receptor (MasR) compared to the liver. The AT1R localised to cancer and stromal infiltrating cells, while other RAS receptors were detected in cancer cells only. Tumor induction led to an initial increase in AT1R and ACE expression while captopril treatment significantly increased ACE expression in the final stages of tumor growth. Conversely, captopril treatment decreased expression of AT1R and angiotensinogen. These results demonstrate significant changes in RAS expression in the tumor-bearing captopril treated liver and in CRC metastases. The data suggests the existence of a tumor-specific RAS that can be independently targeted by RAS blockade

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

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

    2010-03-01

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

  16. 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......S for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma...... levels of BNP. Methods Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril...

  17. Remodelação miocárdica após infarto agudo do miocárdio experimental em ratos: efeito do bloqueio do sistema renina angiotensina aldosterona Myocardial remodeling after experimental acute myocardial infarction in rats: effect of renin-angiotensin-aldosterone system blockade

    Directory of Open Access Journals (Sweden)

    Hindalis Ballesteros Epifanio

    2005-01-01

    greater in the left ventricle of the infarcted group, and its increase was prevented with treatment (LOS=1.16±0.4%, LIS=1.27±0.5%, NT=1.8± 0.4%, CONT=0.7±0.5%. Myocardial hydroxyproline was greater in the infarcted group (NT=6.91±2.98mg/g vs. CONT=2.81± 1.21mg/g and did not change with treatment. CONCLUSION: Myocardial remodeling after infarction is characterized by an increase in the remaining ventricular mass and in interstitial collagen. The angiotensin-converting-enzyme blockers and the selective angiotensin II AT1 antagonist prevent hypertrophy of the myocyte and interstitial fibrosis.

  18. Intramuscular renin-angiotensin system is activated in human muscular dystrophy.

    Science.gov (United States)

    Sun, Guilian; Haginoya, Kazuhiro; Dai, Hongmei; Chiba, Yoko; Uematsu, Mitsugu; Hino-Fukuyo, Naomi; Onuma, Akira; Iinuma, Kazuie; Tsuchiya, Shigeru

    2009-05-15

    To investigate the role of the muscular renin-angiotensin system (RAS) in human muscular dystrophy, we used immunohistochemistry and Western blotting to examine the cellular localization of angiotensin-converting enzyme (ACE), the angiotensin II type 1 receptor (AT1) and the angiotensin II type 2 receptor (AT2) in muscle biopsies from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and congenital muscular dystrophy (CMD). In normal muscle, ACE was expressed in vascular endothelial cells and neuromuscular junctions (NMJs), whereas AT1 was immunolocalized to the smooth muscle cells of blood vessels and intramuscular nerve twigs. AT2 was immunolocalized in the smooth muscle cells of blood vessels. These findings suggest that the RAS has a functional role in peripheral nerves and NMJs. ACE and AT1, but AT2 immunoreactivity were increased markedly in dystrophic muscle as compared to controls. ACE and the AT1 were strongly expressed in the cytoplasm and nuclei of regenerating muscle fibers, fibroblasts, and in macrophages infiltrating necrotic fibers. Double immunolabeling revealed that activated fibroblasts in the endomysium and perimysium of DMD and CMD muscle were positive for ACE and AT1. Triple immunolabeling demonstrated that transforming growth factor-beta1 (TGF-beta1) and ACE were colocalized on the cytoplasm of activated fibroblasts in dystrophic muscle. Furthermore, Western blotting showed increases in the expression of AT1 and TGF-beta1 protein in dystrophic muscle, which coincided with our immunohistochemical results. The overexpression of ACE and AT1 in dystrophic muscle would likely result in the increased production of Ang II, which may act on these cells in an autocrine manner via AT1. The activation of AT1 may induce fibrous tissue formation through overexpression of TGF-beta1, which potently activates fibrogenesis and suppresses regeneration. In conclusion, our results imply that the intramuscular RAS-TGF-beta1 pathway

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

    NARCIS (Netherlands)

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

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

  20. Renin-angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer: The Rotterdam study

    NARCIS (Netherlands)

    R. van der Knaap (Ronald); C. Siemes (Claire); J.W.W. Coebergh (Jan Willem); P. Tikka-Kleemola (Päivi); A. Hofman (Albert); B.H.Ch. Stricker (Bruno)

    2008-01-01

    textabstractBACKGROUND. Angiotensin I-converting enzyme (ACE) inhibitors, angiotensin II antagonists, and the ACE insertion/deletion (I/D) gene polymorphism all influence serum angiotensin II action. Because angiotensin II levels have been associated with cancer, the objective of the current

  1. ALDOSTERONE ANTAGONISTS. MODERN VIEWS ON THE MECHANISM OF ACTION AND EFFECTS OF SPIRONOLACTONE

    Directory of Open Access Journals (Sweden)

    V. I. Podzolkov

    2017-01-01

    Full Text Available The importance of renin-angiotensin-aldosterone system in pathogenesis of different clinical conditions is studied well. The key role of aldosterone receptor blockers, particularly spironolactone, in treatment of such conditions as primary hyperaldosteronism, resistant hypertension, edematous syndrome in congestive heart failure, nephrotic syndrome, and portal cirrhosis is considered in the article. Development of ideas about cardio-, vaso- and nephroprotective effects of these drugs is highlighted as well as their influence on patient prognosis.

  2. Circadian rhythm of blood pressure and the renin-angiotensin system in the kidney.

    Science.gov (United States)

    Ohashi, Naro; Isobe, Shinsuke; Ishigaki, Sayaka; Yasuda, Hideo

    2017-05-01

    Activation of the intrarenal renin-angiotensin system (RAS) has a critical role in the pathophysiology of the circadian rhythm of blood pressure (BP) and renal injury, independent of circulating RAS. Although it is clear that the circulating RAS has a circadian rhythm, reports of a circadian rhythm in tissue-specific RAS are limited. Clinical studies evaluating intrarenal RAS activity by urinary angiotensinogen (AGT) levels have indicated that urinary AGT levels were equally low during both the daytime and nighttime in individuals without chronic kidney disease (CKD) and that urinary AGT levels were higher during the daytime than at nighttime in patients with CKD. Moreover, urinary AGT levels of the night-to-day (N/D) ratio of urinary AGT were positively correlated with the levels of N/D of urinary protein, albumin excretion and BP. In addition, animal studies have demonstrated that the expression of intrarenal RAS components, such as AGT, angiotensin II (AngII) and AngII type 1 receptor proteins, increased and peaked at the same time as BP and urinary protein excretion during the resting phase, and the amplitude of the oscillations of these proteins was augmented in a chronic progressive nephritis animal compared with a control. Thus, the circadian rhythm of intrarenal RAS activation may lead to renal damage and hypertension, which both are associated with diurnal variations in BP. It is possible that augmented glomerular permeability increases AGT excretion levels into the tubular lumen and that circadian fluctuation of glomerular permeability influences the circadian rhythm of the intrarenal RAS.

  3. Renin-Angiotensin Activation and Oxidative Stress in Early Heart Failure with Preserved Ejection Fraction

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    Smita I. Negi

    2015-01-01

    Full Text Available Animal models have suggested a role of renin-angiotensin system (RAS activation and subsequent cardiac oxidation in heart failure with preserved ejection fraction (HFpEF. Nevertheless, RAS blockade has failed to show efficacy in treatment of HFpEF. We evaluated the role of RAS activation and subsequent systemic oxidation in HFpEF. Oxidative stress markers were compared in 50 subjects with and without early HFpEF. Derivatives of reactive oxidative metabolites (DROMs, F2-isoprostanes (IsoPs, and ratios of oxidized to reduced glutathione (Eh GSH and cysteine (Eh CyS were measured. Angiotensin converting enzyme (ACE levels and activity were measured. On univariate analysis, HFpEF was associated with male sex (p=0.04, higher body mass index (BMI (p=0.003, less oxidized Eh CyS (p=0.001, lower DROMs (p=0.02, and lower IsoP (p=0.03. Higher BMI (OR: 1.3; 95% CI: 1.1–1.6 and less oxidized Eh CyS (OR: 1.2; 95% CI: 1.1–1.4 maintained associations with HFpEF on multivariate analysis. Though ACE levels were higher in early HFpEF (OR: 1.09; 95% CI: 1.01–1.05, ACE activity was similar to that in controls. HFpEF is not associated with significant systemic RAS activation or oxidative stress. This may explain the failure of RAS inhibitors to alter outcomes in HFpEF.

  4. Role of Renin-Angiotensin system and oxidative stress on vascular inflammation in insulin resistence model.

    Science.gov (United States)

    Renna, N F; Lembo, C; Diez, E; Miatello, R M

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    N. F. Renna

    2013-01-01

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

  6. Effect of Renin-Angiotensin Blockers on Left Ventricular Remodeling in Severe Aortic Stenosis.

    Science.gov (United States)

    Goh, Serene Si-Ning; Sia, Ching-Hui; Ngiam, Nicholas Jinghao; Tan, Benjamin Yong-Qiang; Lee, Poay Sian; Tay, Edgar Lik-Wui; Kong, William Kok-Fai; Yeo, Tiong Cheng; Poh, Kian-Keong

    2017-06-01

    Studies have shown that medical therapy with renin-angiotensin blockers (RABs) may benefit patients with aortic stenosis (AS). However, its use and efficacy remains controversial, including in patients with low flow (LF) with preserved left ventricular ejection fraction (LVEF). We examined the effects of RAB use on LV remodeling in patients with severe AS with preserved LVEF, analyzing the differential effects in patients with LF compared with normal flow (NF). This is a retrospective study of 428 consecutive subjects from 2005 to 2014 with echocardiographic diagnosis of severe AS and preserved LVEF. Clinical and echocardiographic parameters were systematically collected and analyzed. Two hundred forty-two (57%) patients had LF. Sixty-four LF patients (26%) were treated with RAB. Patients on RAB treatment had a higher incidence of hyperlipidemia (69% vs 44%) and diabetes mellitus (53% vs 34%). Severity of AS in terms of valve area, transvalvular mean pressure gradient, and aortic valve resistance were similar between both groups as was the degree of LV diastolic function. The RAB group demonstrated significantly lower LV mass index with a correspondingly lower incidence of concentric LV hypertrophy. Regardless of the duration of RAB therapy, patients had increased odds of having a preserved LV mass index compared with those without RAB therapy. In conclusion, RAB therapy may be associated with less LV pathological remodeling and have a role in delaying patients from developing cardiovascular complications of AS. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The physiology of a local renin-angiotensin system in the pancreas.

    Science.gov (United States)

    Leung, Po Sing

    2007-04-01

    The systemic renin-angiotensin system (RAS) plays an important role in regulating blood pressure, electrolyte and fluid homeostasis. However, local RASs also exist in diverse tissues and organs, where they play a multitude of autocrine, paracrine and intracrine physiological roles. The existence of a local RAS is now recognized in pancreatic acinar, islet, duct, endothelial and stellate cells, the expression of which is modulated in response to physiological and pathophysiological stimuli such as hypoxia, pancreatitis, islet transplantation, hyperglycaemia, and diabetes mellitus. This pancreatic RAS has been proposed to have important endocrine and exocrine roles in the pancreas, regulating local blood flow, duct cell sodium bicarbonate secretion, acinar cell digestive enzyme secretion, islet beta-cell (pro)insulin biosynthesis, and thus, glucose-stimulated insulin release, delta-cell somatostatin secretion, and pancreatic cell proliferation and differentiation. It may further mediate oxidative stress-induced cell inflammation, apoptosis and fibrosis. Further exploration of this system would probably offer new insights into the pathogenesis of pancreatitis, diabetes, cystic fibrosis and pancreatic cancer formation. New therapeutic targets and strategies might thus be suggested.

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

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    Daméhan Tchelougou

    2015-01-01

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

  9. 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

  10. Interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats.

    Science.gov (United States)

    Yang, Ke-Ke; Sui, Yi; Zhou, Hui-Rong; Zhao, Hai-Lu

    2017-05-01

    Renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin-angiotensin system and adenosine monophosphate-activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Renal adenosine monophosphate-activated protein kinase and its downstream molecule acetyl coenzyme A carboxylase were detected by immunohistochemistry and western blot at 10 months after uninephrectomy. Meanwhile, we examined renal carcinogenesis by histological transformation and expressions of Ki67 and mutant p53. During the study, fasting lipid profiles were detected dynamically at 3, 6, 8, and 10 months. The results indicated that adenosine monophosphate-activated protein kinase expression in uninephrectomized rats showed 36.8% reduction by immunohistochemistry and 89.73% reduction by western blot. Inversely, acetyl coenzyme A carboxylase expression increased 83.3% and 19.07% in parallel to hyperlipidemia at 6, 8, and 10 months. The histopathology of carcinogenesis in remnant kidneys was manifested by atypical proliferation and carcinoma in situ, as well as increased expressions of Ki67 and mutant p53. Intervention with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker significantly prevented the inhibition of adenosine monophosphate-activated protein kinase signaling pathway and renal carcinogenesis in uninephrectomized rats. In conclusion, the novel findings suggest that uninephrectomy-induced disturbance in adenosine monophosphate-activated protein kinase signaling pathway resulted in hyperlipidemia and

  11. Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride.

    Science.gov (United States)

    Graudal, Niels Albert; Hubeck-Graudal, Thorbjorn; Jurgens, Gesche

    2017-04-09

    In spite of more than 100 years of investigations the question of whether a reduced sodium intake improves health is still unsolved. To estimate the effects of low sodium intake versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides. The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to March 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the reference lists of relevant articles. Studies randomising persons to low-sodium and high-sodium diets were included if they evaluated at least one of the above outcome parameters. Two review authors independently collected data, which were analysed with Review Manager 5.3. A total of 185 studies were included. The average sodium intake was reduced from 201 mmol/day (corresponding to high usual level) to 66 mmol/day (corresponding to the recommended level).The effect of sodium reduction on blood pressure (BP) was as follows: white people with normotension: SBP: mean difference (MD) -1.09 mmHg (95% confidence interval (CI): -1.63 to -0.56; P = 0.0001); 89 studies, 8569 participants; DBP: + 0.03 mmHg (MD 95% CI: -0.37 to 0.43; P = 0.89); 90 studies, 8833 participants. High-quality evidence. Black people with normotension: SBP: MD -4.02 mmHg (95% CI:-7.37 to -0.68; P = 0.002); seven studies, 506 participants; DBP: MD -2.01 mmHg (95% CI:-4.37 to 0.35; P = 0.09); seven studies, 506 participants. Moderate-quality evidence. Asian people with normotension: SBP: MD -0.72 mmHg (95% CI: -3.86 to 2.41; P = 0.65); DBP: MD -1.63 mmHg (95% CI:-3.35 to 0

  12. Prospective validation of an automated chemiluminescence-based assay of renin and aldosterone for the work-up of arterial hypertension.

    Science.gov (United States)

    Rossi, Gian Paolo; Ceolotto, Giulio; Rossitto, Giacomo; Seccia, Teresa Maria; Maiolino, Giuseppe; Berton, Chiara; Basso, Daniela; Plebani, Mario

    2016-09-01

    The availability of simple and accurate assays of plasma active renin (DRC) and aldosterone concentration (PAC) can improve the detection of secondary forms of arterial hypertension. Thus, we investigated the performance of an automated chemiluminescent assay for DRC and PAC in referred hypertensive patients. We prospectively recruited 260 consecutive hypertensive patients referred to an ESH Center for Hypertension. After exclusion of six protocol violations, 254 patients were analyzed: 67.3% had primary hypertension, 17.3% an aldosterone producing adenoma (APA), 11.4% idiopathic hyperaldosteronism (IHA), 2.4% renovascular hypertension (RVH), 0.8% familial hyperaldosteronism type 1 (FH-1), 0.4% apparent mineralocorticoid excess (AME), 0.4% a renin-producing tumor, and 3.9% were adrenalectomized APA patients. Bland-Altman plots and Deming regression were used to analyze results. The diagnostic accuracy (area under the curve, AUC of the ROC) of the DRC-based aldosterone-renin ratio (ARRCL) was compared with that of the PRA-based ARR (ARRRIA) using as reference the conclusive diagnosis of APA. At Bland-Altman plot, the DRC and PAC assay showed no bias as compared to the PRA and PAC assay. A tight relation was found between the DRC and the PRA values (concordance correlation coefficient=0.92, pAPA identification the AUC of the ARRCL was higher than that of the ARRRIA [0.974 (95% CI 0.940-0.991) vs. 0.894 (95% CI 0.841-0.933), p=0.02]. This rapid automated chemiluminescent DRC/PAC assay performed better than validated PRA/PAC radioimmunoassays for the identification of APA in referred hypertensive patients.

  13. A case of low renin hyperaldosteronism considered to be aldosterone-producing adrenocortical adenoma by CT image of adrenal gland

    International Nuclear Information System (INIS)

    Hayashi, Kozo; Tsuchihashi, Yoshihiro; Ito, Kazuro; Ozono, Noboru

    1983-01-01

    A case was reported in which hypertension, hypopotassemia, low plasma renin activity and hyperaldosteronemia were observed. Imaging suggested adrenocortical adenoma, leading to the diagnosis of low renin hyperaldosteronism. (Chiba, N.)

  14. Inhibition of the Renin-Angiotensin-Aldosterone System for Cerebrorenal Protection

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo; Toyoda, K

    2013-01-01

    Blood pressure is a strong risk factor for ischemic and atherosclerotic events such as stroke. Blood pressure is often elevated in patients with chronic kidney disease. Consequently, chronic kidney disease patients are at high risk of developing cardiovascular and cerebrovascular damage. Blood

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  16. A case of posterior reversible encephalopathy syndrome in the setting of post-partum preeclampsia with suppressed plasma aldosterone levels and plasma renin activity

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    Aurelio Negro

    2013-12-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is characterized by headache, altered mental status, visual loss, and seizures. PRES is associated with neuroradiological findings: white matter abnormalities, predominantly in the parieto-occipital regions of the brain. PRES has been described in association with hypertensive encephalopathy, eclampsia, renal failure, or following immunosuppressive or anticancer therapy. We report a case of PRES in a severe preeclampsia occurring in the late postpartum period, with suppressed plasma aldosterone levels and plasma renin activity. These laboratory abnormalities may be due to an apparent mineralocorticoid excess syndrome.

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

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    Giuseppina Mattace Raso

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

  18. Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

    Directory of Open Access Journals (Sweden)

    E.P. Velloso

    2007-04-01

    Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

  19. Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

    Directory of Open Access Journals (Sweden)

    E.P. Velloso

    Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

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

    Science.gov (United States)

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

    2011-05-15

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

  1. The role of the renin-angiotensin system in the development of insulin resistance in skeletal muscle.

    Science.gov (United States)

    Henriksen, Erik J; Prasannarong, Mujalin

    2013-09-25

    The canonical renin-angiotensin system (RAS) involves the initial action of renin to cleave angiotensinogen to angiotensin I (ANG I), which is then converted to ANG II by the angiotensin converting enzyme (ACE). ANG II plays a critical role in numerous physiological functions, and RAS overactivity underlies many conditions of cardiovascular dysregulation. In addition, ANG II, by acting on both endothelial and myocellular AT1 receptors, can induce insulin resistance by increasing cellular oxidative stress, leading to impaired insulin signaling and insulin-stimulated glucose transport activity. This insulin resistance associated with RAS overactivity, when coupled with progressive ß-cell dysfunction, eventually leads to the development of type 2 diabetes. Interventions that target RAS overactivity, including ACE inhibitors, ANG II receptor blockers, and, most recently, renin inhibitors, are effective both in reducing hypertension and in improving whole-body and skeletal muscle insulin action, due at least in part to enhanced Akt-dependent insulin signaling and insulin-dependent glucose transport activity. ANG-(1-7), which is produced from ANG II by the action of ACE2 and acts via Mas receptors, can counterbalance the deleterious actions of the ACE/ANG II/AT1 receptor axis on the insulin-dependent glucose transport system in skeletal muscle. This beneficial effect of the ACE2/ANG-(1-7)/Mas receptor axis appears to depend on the activation of Akt. Collectively, these findings underscore the importance of RAS overactivity in the multifactorial etiology of insulin resistance in skeletal muscle, and provide support for interventions that target the RAS to ameliorate both cardiovascular dysfunctions and insulin resistance in skeletal muscle tissue. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Active immunization against renin in normotensive marmoset

    International Nuclear Information System (INIS)

    Michel, J.B.; Guettier, C.; Philippe, M.; Galen, F.X.; Corvol, P.; Menard, J.

    1987-01-01

    Primate renins (human and monkey) are very similar. We used pure human renin to immunize marmosets (Callithrix jacchus) and thereby produce a chronic blockade of the renin-angiotensinogen reaction. After a control period of 2 months, five male marmosets, on their usual sodium-poor diet, were immunized against pure human renin by three subcutneous injections of 30 μg each, with complete and then incomplete Freund's adjuvant. Three marmosets were injected with adjuvant only and served as controls. Blood sampling and blood pressure measurements were performed weekly. After the third injection, the five marmosets immunized against renin developed a high titer of renin antibodies (50% binding of 125 I-labeled human renin at a dilution of ≥ 1:10,000). The antibodies inhibited the enzymatic activity of both marmoset and human renins. At the same time, systolic blood pressure decreased significantly. Plasma renin enzyme activity was undetectable in the animals. Plasma aldosterone decreased significantly. After 1-4 months with low blood pressure, a normal urinary output, and a normal plasma creatinine, the five marmosets became sick and died within one month. At autopsy an immunological renal disease, characterize by the presence of immunoglobulin and macrophage infiltration colocalized with renin, was found. No immunoglobulin was detectable in extrarenal vessels or in other organs. These experiments demonstrate that, in this primate, a chronic blockade of the renin-angiotensin system can be achieved by active immunization against homologous renin, but this blockade is associated with the development of an autoimmune disease localized in the kidney

  3. Study on plasma levels of brain natriuretic peptide, angiotensin and aldosterone in patients with congestive heart failure

    International Nuclear Information System (INIS)

    Cheng Yu; Hong Liquan; Chen Zhaojun

    2009-01-01

    Objective: To investigate the relationship between brain natriuretic peptide (BNP), angiotensin (AT-II), and aldosterone (ALD) levels in patients with congestive heart failure (CHF). Methods: Plasma levels of BNP (with CLIA) and Angiotensin II (AT-II), aldosterone (ALD) (with RIA) were measured in 98 patients with CHF, 76 cardiac patients without heart faclure, and 86 controls. Results: The plasma levels of BNP, AT-II and ALD in patients (with RIA) CHF were significantly higher than those in the controls. The levels of BNP, AT-II and ALD, CHF patients after therapy were markedly dropped and were significantly lower than those patients before therapy (P<0.01). BNP levels were positively correlated with AT-II and ALD in levels CHF (P<0.05). Conclusion: The over activity of RAA systems may be one of the mechanisms of heart failure. Dynamic observation of changes of BNP, AT-II and ALD may be very useful in assessment of severity and prognosis of patients with CHF. (authors)

  4. CHANGES IN THE LEVELS OF ANGIOTENSIN II, ALDOSTERONE, AND FIBROBLAST GROWTH FACTOR IN PATIENTS WITH RHEUMATOID ARTHRITIS IN RELATION TO CLINICAL FEATURES

    Directory of Open Access Journals (Sweden)

    E. B. Komarova

    2016-01-01

    Full Text Available Angiotensin II, aldosterone, and fibroblast growth factor (FGF stimulate neoangiogenesis, fibroblast proliferation, and elaboration of proinflammatory cytokines, which in turn contributes to increased pannus mass and the development of joint tissue destruction in rheumatoid arthritis (RA.Objective: to establish the specific features of changes in the blood levels of angiotensin II, aldosterone, and FGF in patients with RA in relation to the duration and severity of the disease.Subjects and methods. Examinations were made in 194 patients diagnosed with RA without comorbidity; the patients’ mean age was 47.7±10.2 years; the disease duration was 3.82±3.43 years. DAS28 scores for RA were calculated based on C-reactive protein levels. An enzyme immunoassay was used to determine the serum levels of anti-cyclic citrullinated peptide antibodies (ACCPA, angiotensin II, aldosterone, and FGF.Results and discussion. All the examinees were ascertained to have increases in the concentration of angiotensin II and aldosterone in blood by twice and in that of FGF by 2.5 times compared to the controls (p < 0.05. In patients with a RA duration of < 2 years, the blood level of angiotensin II was 25% higher than in those with a RA duration of > 5 years and the concentrations of aldosterone and FGF in patients with long-term RA were twice as high as in those with early RA. In patients with high RA activity, the blood level of angiotensin II was 1.5-fold higher than in those with low and moderate disease activity (p < 0.05. In patients with a high blood ACCPA level, the concentrations of angiotensin II, aldosterone, and FGF were 20, 30, and 25%, respectively, higher than in those with low ACCPA levels. The correlation of DAS28 with blood angiotensin II levels increased with enhanced RA activity. The high aldosterone and FGF values in RA patients are associated with the progression of joint radiographic changes.

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

    DEFF Research Database (Denmark)

    Persson, Frederik; Lindhardt, Morten; Rossing, Peter

    2016-01-01

    Hypothesis/objectives: Early prevention of diabetic nephropathy by way of blocking the renin-angiotensin system (RAS) in patients with normoalbuminuria seems rational, but trials have so far shown conflicting results. The present meta-analysis was undertaken to investigate if such treatment can...... prevent development of microalbuminuria. Materials and methods: We searched MEDLINE, EMBASE and the Cochrane Library (2 June 2014) for randomised controlled trials, with a population of patients with type 2 diabetes and normoalbuminuria, comparing angiotensin-converting enzyme inhibitors (ACEis......-cause mortality(p=0.07). Conclusions: We conclude that in patients with type 2 diabetes and normoalbuminuria, early intervention with ACEis or ARBs reduces the risk for development of microalbuminuria....

  6. THE RENIN-ANGIOTENSIN SYSTEM AND THE BIOLOGY OF SKELETAL MUSCLE: MECHANISMS OF MUSCLE WASTING IN CHRONIC DISEASE STATES.

    Science.gov (United States)

    Delafontaine, Patrice; Yoshida, Tadashi

    2016-01-01

    Sarcopenia and cachexia are muscle-wasting syndromes associated with aging and with many chronic diseases such as congestive heart failure, diabetes, cancer, chronic obstructive pulmonary disease, and renal failure. While mechanisms are complex, these conditions are often accompanied by elevated angiotensin II (Ang II). We found that Ang II infusion in rodents leads to skeletal muscle wasting via alterations in insulin-like growth factor-1 signaling, increased apoptosis, enhanced muscle protein breakdown via the ubiquitin-proteasome system, and decreased appetite resulting from downregulation of hypothalamic orexigenic neuropeptides orexin and neuropeptide Y. Furthermore, Ang II inhibits skeletal muscle stem cell proliferation, leading to lowered muscle regenerative capacity. Distinct stem cell Ang II receptor subtypes are critical for regulation of muscle regeneration. In ischemic mouse congestive heart failure model skeletal muscle wasting and attenuated muscle regeneration are Ang II dependent. These data suggest that the renin-angiotensin system plays a critical role in mechanisms underlying cachexia in chronic disease states.

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

    International Nuclear Information System (INIS)

    Abreu Fagundes, V.G. de.

    1984-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Therese Featherston

    2016-09-01

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

  9. Renin-angiotensin system (RAS) blockade attenuates growth and metastatic potential of renal cell carcinoma in mice.

    Science.gov (United States)

    Araújo, Wedson F; Naves, Marcelo A; Ravanini, Juliana N; Schor, Nestor; Teixeira, Vicente P C

    2015-09-01

    Renal cell carcinoma (RCC) is the most frequent type of cancer among renal neoplasms in adults and responds poorly to radiotherapy and chemotherapy. There is evidence that blockade of the renin-angiotensin system (RAS) might have antineoplastic effects. The aim of this study was to investigate the effects of RAS blockade on RCC in a murine model. Murine renal cancer cells (Renca) were injected (1 × 10(5)) into the subcapsular space of the left kidney of BALB/c mice (8 wk of age). The animals were divided into 4 groups: a control group (no treatment), angiotensin-receptor blockers group (losartan 100mg/kg/d), angiotensin-converting enzyme inhibitor group (captopril 10mg/kg/d), and angiotensin-receptor blockers +angiotensin-converting enzyme inhibitor group (losartan 100mg/kg/d +captopril 10mg/kg/d). The animals received the drugs by gavage for 21 days after inoculation, beginning 2 days before tumor induction, and were then euthanized. After killing the animals, the kidneys and lungs were removed, weighed, and processed for histopathological and immunohistochemical analyses. Angiogenesis and vascular microvessels were assessed with the antibodies anti-vascular endothelial growth factor and anti-CD34. Angiotensin II-inoculated animals developed renal tumors. Treated animals presented smaller tumors, regardless of the therapeutic regimen, and far fewer lung metastases in both quantity and dimension compared with the controls. The expression of vascular endothelial growth factor and CD34 were significantly decreased in renal tumors of treated animals compared with the controls. Our findings suggest that blockade of RAS decreases tumor proliferation and metastatic capacity of RCC in this experimental model. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik

    2009-01-01

    Hypoglycaemia is an unavoidable side effect to insulin therapy of diabetes. In daily life some hypoglycaemic episodes are recognised by the patients and corrected by ingestion of glucose, but occasionally unrecognised episodes progress into severe hypoglycaemia with cognitive impairment and the n......Hypoglycaemia is an unavoidable side effect to insulin therapy of diabetes. In daily life some hypoglycaemic episodes are recognised by the patients and corrected by ingestion of glucose, but occasionally unrecognised episodes progress into severe hypoglycaemia with cognitive impairment...... both subjects at low and at high risk within a one-year period were identified. Preliminary data suggest that this is explained by impaired capability of subjects with high renin-angiotensin system activity to maintain cognitive function during hypoglycaemia. The clinical implications of this finding...... which, however, must await additional independent confirmation, include prediction and possibly some prevention of severe hypoglycaemia. An evaluation of renin-angiotensin system activity may - together with assessment of other risk factors - contribute to rational individualized setting of glycaemic...

  11. Expression of genes of the cardiac and renal renin-angiotensin systems in preterm piglets: is this system a suitable target for therapeutic intervention?

    Science.gov (United States)

    Kim, Eleanor; Eiby, Yvonne; Lumbers, Eugenie; Boyce, Amanda; Gibson, Karen; Lingwood, Barbara

    2015-10-01

    The newborn circulating, cardiac and renal renin-angiotensin systems (RASs) are essential for blood pressure control, and for cardiac and renal development. If cardiac and renal RASs are immature this may contribute to cardiovascular compromise in preterm infants. This study measured mRNA expression of cardiac and renal RAS components in preterm, glucocorticoid (GC) exposed preterm, and term piglets. Renal and cardiac RAS mRNA levels were measured using real-time polymerase chain reaction (PCR). Genes studied were: (pro)renin receptor, renin, angiotensinogen, angiotensin converting enzyme (ACE), ACE2, angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R). All the genes studied were expressed in the kidney; neither renin nor AT2R mRNA were detected in the heart. There were no gestational changes in (pro)renin receptor, renin, ACE or AT1R mRNA levels. Right ventricular angiotensinogen mRNA levels in females were lower in preterm animals than at term, and GC exposure increased levels in male piglets. Renal angiotensinogen mRNA levels in female term piglets were lower than females from both preterm groups, and lower than male term piglets. Left ventricular ACE2 mRNA expression was lower in GC treated preterm piglets. Renal AT2R mRNA abundance was highest in GC treated preterm piglets, and the AT1R/AT2R ratio was increased at term. Preterm cardiac and renal RAS mRNA levels were similar to term piglets, suggesting that immaturity of these RASs does not contribute to preterm cardiovascular compromise. Since preterm expression of both renal and cardiac angiotensin II-AT1R is similar to term animals, cardiovascular dysfunction in the sick preterm human neonate might be effectively treated by agents acting on their RASs. © The Author(s), 2015.

  12. The protective arm of the renin-angiotensin system may counteract the intense inflammatory process in fetuses with posterior urethral valves.

    Science.gov (United States)

    Rocha, Natalia P; Bastos, Fernando M; Vieira, Érica L M; Prestes, Thiago R R; Silveira, Katia D da; Teixeira, Mauro M; Simões E Silva, Ana Cristina

    2018-03-11

    Posterior urethral valve is the most common lower urinary tract obstruction in male children. A high percentage of patients with posterior urethral valve evolve to end-stage renal disease. Previous studies showed that cytokines, chemokines, and components of the renin-angiotensin system contribute to the renal damage in obstructive uropathies. The authors recently found that urine samples from fetuses with posterior urethral valve have increased levels of inflammatory molecules. The aim of this study was to measure renin-angiotensin system molecules and to investigate their correlation with previously detected inflammatory markers in the same urine samples of fetuses with posterior urethral valve. Urine samples from 24 fetuses with posterior urethral valve were collected and compared to those from 22 healthy male newborns at the same gestational age (controls). Renin-angiotensin system components levels were measured by enzyme-linked immunosorbent assay. Fetuses with posterior urethral valve presented increased urinary levels of angiotensin (Ang) I, Ang-(1-7) and angiotensin-converting enzyme 2 in comparison with controls. ACE levels were significantly reduced and Ang II levels were similar in fetuses with posterior urethral valve in comparison with controls. Increased urinary levels of angiotensin-converting enzyme 2 and of Ang-(1-7) in fetuses with posterior urethral valve could represent a regulatory response to the intense inflammatory process triggered by posterior urethral valve. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  13. Study on the dynamic changes of the renin angiotensin system (RAS) in patients with acute pancreatitis

    International Nuclear Information System (INIS)

    An Yuliang; Zhou Li

    2002-01-01

    Objective: To assess the severity of acute pancreatitis (AP) by observing the changes of the plasma renin activity (PRA) and plasma angiotensin-II levels in those patients. Methods: Plasma concentrations of the PRA and AGT-II were determined with RIA in patients with severe acute pancreatitis (SAP), mild acute pancreatitis (MAP), acute cholecystitis (AC), acute appendicitis (AA), acute phase of peptic ulcer (PU, only AGT-II was measured) and in healthy controls (HC). In SAP and MAP patients, a second determination was done. Results: The plasma levels of the PRA and AGT-II within 24 hours after admission were 3.84 ±1.92 ng/ml·h, 386.68 ±178.53 pg/ml in SAP. A group; 1.88 ± 0.93 ng/ml·h, 142.68 ± 83.57 pg/ml in MAP. A group; 0.68 ±0.45 ng/ml·h, 43.51 ± 31.04 pg/ml in HC group. These variables are significantly higher in SAP. A and MAP. A groups than those in other groups. During the recovery period, they were 1.34 ± 0.76 ng/ml·h, 44.71 ± 27.93 pg/ml in SAP. R group, and 1.18 ± 0.69 ng/ml·h, 41.82 ± 17.88 pg/ml in MAP. R group. There were significant differences (p < 0.05) when comparing the SAP. A group with MAP. A group, and comparing HC group with SAP. A group and with MAP. A group respectively. The paired compartment of the AP (SAP. R/SAP. A and MAP. R/MAP. A) are also significantly differences (p < 0.05). For the same group of AP patients at different stage (SAP. R/SAP. A and MAP. R/MAP. A) those were also significant difference (p < 0.05 ). There are also significant (p < 0.05) difference comparing those values in SAP. A and MAP. A group with the AC, AA and PU group respectively. Conclusion: 1. RAAS are activated in patients with AP on account of the circulatory hypovolemia with various causes. The degree of activation is positively correlated to the seriousness of the disease process. Increase of the plasma level of AGT-II in patients with AP is a compensatory mechanism but it exacerbates the microcirculation impediment of the pancreas

  14. 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....... In addition, combination treatment seemed safe and effective also in patients with impaired kidney function. These initial findings formed the basis for the design of a large morbidity and mortality trial investigating aliskiren as add-on to standard treatment. The study has just concluded, but was terminated...... 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...

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

    DEFF Research Database (Denmark)

    Schievink, B; Kröpelin, T; Mulder, S

    2016-01-01

    AIMS: To develop and validate a model to simulate progression of diabetic kidney disease (DKD) from early onset until end-stage renal disease (ESRD), and to assess the effect of renin-angiotensin system (RAS) intervention in early, intermediate and advanced stages of DKD. METHODS: We used data from...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    INTRODUCTION: High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patient...

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

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

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

  19. A local renal renin-angiotensin system activation via renal uptake of prorenin and angiotensinogen in diabetic rats.

    Science.gov (United States)

    Tojo, Akihiro; Kinugasa, Satoshi; Fujita, Toshiro; Wilcox, Christopher S

    2016-01-01

    The mechanism of activation of local renal renin-angiotensin system (RAS) has not been clarified in diabetes mellitus (DM). We hypothesized that the local renal RAS will be activated via increased glomerular filtration and tubular uptake of prorenin and angiotensinogen in diabetic kidney with microalbuminuria. Streptozotocin (STZ)-induced DM and control rats were injected with human prorenin and subsequently with human angiotensinogen. Human prorenin uptake was increased in podocytes, proximal tubules, macula densa, and cortical collecting ducts of DM rats where prorenin receptor (PRR) was expressed. Co-immunoprecipitation of kidney homogenates in DM rats revealed binding of human prorenin to the PRR and to megalin. The renal uptake of human angiotensinogen was increased in DM rats at the same nephron sites as prorenin. Angiotensin-converting enzyme was increased in podocytes, but decreased in the proximal tubules in DM rats, which may have contributed to unchanged renal levels of angiotensin despite increased angiotensinogen. The systolic blood pressure increased more after the injection of 20 μg of angiotensinogen in DM rats than in controls, accompanied by an increased uptake of human angiotensinogen in the vascular endothelium. In conclusion, endocytic uptake of prorenin and angiotensinogen in the kidney and vasculature in DM rats was contributed to increased tissue RAS and their pressor response to angiotensinogen.

  20. Central role for sodium in the pathogenesis of blood pressure changes independent of angiotensin, aldosterone and catecholamines in type 1 (insulin-dependent) diabetes mellitus

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B; Mathiesen, E R; Deckert, T

    1987-01-01

    .41, p less than 0.01). Extracellular volume was increased in patients (p less than 0.05), whereas plasma volume was normal. Supine serum angiotensin II was suppressed in the patients (p less than 0.001). A negative correlation was found between mean blood pressure and supine serum aldosterone (n = 68, r...... = -0.24, p less than 0.05), and exchangeable sodium and aldosterone (n = 66, r = -0.36, p less than 0.002) in all patients. The catecholamine levels were also suppressed or normal in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)...

  1. Preadmission use of renin-angiotensin blockers and rupture of abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Wemmelund, Holger; Høgh, Annette; Hundborg, Heidi H.

    2016-01-01

    PURPOSE: Rupture of abdominal aortic aneurysms (rAAA) is associated with high mortality. Use of angiotensin converting enzyme inhibitors (ACE-inhibitors) and angiotensin receptor blockers (ARBs) has been suggested to reduce the risk of rAAA. This nationwide, combined case-control and follow-up st...

  2. Embryonic Stem Cell-Like Population in Dupuytren’s Disease Expresses Components of the Renin-Angiotensin System

    Directory of Open Access Journals (Sweden)

    Nicholas On

    2017-07-01

    Full Text Available Background:. The renin-angiotensin system (RAS mediates cardiac and renal fibrosis. Dupuytren’s disease (DD is a proliferative fibromatosis affecting the hands. This study investigated the expression of the RAS in DD. Methods:. 3,3-Diaminobenzidine (DAB and immunofluorescent immunohistochemical (IHC staining for (prorenin receptor (PRR, angiotensin-converting enzyme (ACE, angiotensin II receptor 1 (ATIIR1, and angiotensin II receptor 2 (ATIIR2 was performed on 4-μm thick formalin-fixed paraffin-embedded sections of DD cords and nodules from 6 patients. Western blotting (WB and NanoString mRNA analysis were performed to confirm RAS protein expression and transcriptional activation, respectively. Results:. IHC staining demonstrated the expression of PRR, ACE, ATIIR1, and ATIIR2 on the ERG+ and CD34+ endothelium of the micro vessels surrounding the DD cords and nodules. PRR was also expressed on the pericyte layer of these microvessels. WB confirmed protein expression of PRR, ACE, and ATIIR2 but not ATIIR1. NanoString analysis confirmed transcriptional activation of PRR, ACE, ATIIR1, but ATIIR2 was below detectable levels. Conclusions:. We demonstrated expression of PRR, ATIIR1, ATIIR2, and ACE on the embryonic stem cell–like cell population on the microvessels surrounding DD nodules and cords by IHC staining, although the expression of ATIIR1 was not confirmed by WB and that of ATIIR2 was below detectable levels on NanoString analysis. These findings suggest the embryonic stem cell–like cell population as a potential therapeutic target for DD, by using RAS modulators.

  3. [Aldosterone response to various stimuli in hyperthyroidism: in vivo and in vitro studies].

    Science.gov (United States)

    Kigoshi, T; Kaneko, M; Nakano, S; Azukizawa, S; Uchida, K; Morimoto, S

    1993-06-20

    Responses of plasma aldosterone (PA) to alpha-ACTH-(1-24) (250 micrograms, im) injection and graded angiotensin II (AII) infusions (2, 4 and 8ng/kg/min for 30 min at each dose) on a constant sodium intake (170mEq daily) were assessed in 17 patients with Basedow's disease and 13 age-matched normal subjects. Aldosterone production in response to ACTH, AII and potassium in adrenal zona glomerulosa cells from L-thyroxine-induced hyperthyroid rats (H-rats) were also examined. Basal levels of plasma renin activity (PRA) and urinary aldosterone excretion were significantly higher (p metabolic clearance rate of aldosterone, may be involved in the abnormal aldosterone metabolism in hyperthyroidism.

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

    Science.gov (United States)

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

    2016-01-01

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

  5. Angiotensin AT1-receptor blockers and cerebrovascular protection: do they actually have a cutting edge over angiotensin-converting enzyme inhibitors?

    DEFF Research Database (Denmark)

    Oprisiu-Fournier, Roxana; Faure, Sébastien; Mazouz, Hakim

    2009-01-01

    First, an update of the vascular systemic and tissue renin-angiotensin-aldosterone system is provided to explain how it is regulated at the systemic and tissue levels, and how many angiotensin peptides and receptors can be modulated by the various antihypertensive drugs. Second, experimental data...... stroke prevention trial PRoFESS, most trials support the hypothesis that angiotensin II-increasing drugs confer specific blood pressure-independent brain ischemia protection when compared with angiotensin II-decreasing drugs or placebo. A careful analysis of the PRoFESS trial, however, reveals study...

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

    Directory of Open Access Journals (Sweden)

    Divya Bhadoo

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-05-20

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

  8. Resveratrol promotes regression of renal carcinoma cells via a renin-angiotensin system suppression-dependent mechanism.

    Science.gov (United States)

    Li, Jianchang; Qiu, Mingning; Chen, Lieqian; Liu, Lei; Tan, Guobin; Liu, Jianjun

    2017-02-01

    The aim of the present study was to investigate the effect of resveratrol on renal carcinoma cells and explore possible renin-angiotensin system-associated mechanisms. Subsequent to resveratrol treatment, the cell viability, apoptosis rate, cytotoxicity levels, caspase 3/7 activity and the levels of angiotensin II (AngII), AngII type 1 receptor (AT1R), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) were evaluated in renal carcinoma cells. The effects of AngII, AT1R, VEGF and COX-2 on resveratrol-induced cell growth inhibition and apoptosis were also examined. The results indicated that resveratrol treatment may suppress growth, induce apoptosis, and decrease AngII, AT1R, VEGF and COX-2 levels in renal carcinoma ACHN and A498 cells. In addition, resveratrol-induced cell growth suppression and apoptosis were reversed when co-culturing with AT1R or VEGF. Thus, resveratrol may suppress renal carcinoma cell proliferation and induce apoptosis via an AT1R/VEGF pathway.

  9. What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders?

    Institute of Scientific and Technical Information of China (English)

    Maria; da; Graa; Naffah-Mazzacoratti; Telma; Luciana; Furtado; Gouveia; Priscila; Santos; Rodrigues; Simōes; Sandra; Regina; Perosa

    2014-01-01

    The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors(B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system(RAS) is an important blood pressure regulator and controls both sodium and water intake. AngⅡ is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngⅡ acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.

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

    Directory of Open Access Journals (Sweden)

    Rondineli Mendes da Silva

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

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

    Directory of Open Access Journals (Sweden)

    Manisha Nautiyal

    2013-01-01

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

  12. Maternal hyperthyroidism alters the pattern of expression of cardiac renin-angiotensin system components in rat offspring.

    Science.gov (United States)

    Lino, Caroline A; Shibata, Caroline E R; Barreto-Chaves, Maria Luiza M

    2014-03-01

    Changes in perinatal environment can lead to physiological, morphological, or metabolic alterations in adult life. It is well known that thyroid hormones (TH) are critical for the development, growth, and maturation of organs and systems. In addition, TH interact with the renin-angiotensin system (RAS), and both play a critical role in adult cardiovascular function. The objective of this study was to evaluate the effect of maternal hyperthyroidism on cardiac RAS components in pups during development. From gestational day nine (GD9), pregnant Wistar rats received thyroxine (T4, 12 mg/l in tap water; Hyper group) or vehicle (control group). Dams and pups were killed on GD18 and GD20. Serum concentrations of triiodothyronine (T3) and T4 were higher in the Hyper group than in the control group dams. Cardiac hypertrophy was observed in Hyper pups on GD20. Cardiac angiotensin-converting enzyme (ACE) activity was significantly lower in Hyper pups on both GD18 and GD20, but there was no difference in Ang I/Ang II levels. Ang II receptors expression was higher in the Hyper pup heart on GD18. Maternal hyperthyroidism is associated with alterations in fetal development and altered pattern of expression in RAS components, which in addition to cardiac hypertrophy observed on GD20 may represent an important predisposing factor to cardiovascular diseases in adult life.

  13. Rapid Induction of Aldosterone Synthesis in Cultured Neonatal Rat Cardiomyocytes under High Glucose Conditions

    Directory of Open Access Journals (Sweden)

    Masami Fujisaki

    2013-01-01

    Full Text Available In addition to classical adrenal cortical biosynthetic pathway, there is increasing evidence that aldosterone is produced in extra-adrenal tissues. Although we previously reported aldosterone production in the heart, the concept of cardiac aldosterone synthesis remains controversial. This is partly due to lack of established experimental models representing aldosterone synthase (CYP11B2 expression in robustly reproducible fashion. We herein investigated suitable conditions in neonatal rat cardiomyocytes (NRCMs culture system producing CYP11B2 with considerable efficacy. NRCMs were cultured with various glucose doses for 2–24 hours. CYP11B2 mRNA expression and aldosterone concentrations secreted from NRCMs were determined using real-time PCR and enzyme immunoassay, respectively. We found that suitable conditions for CYP11B2 induction included four-hour incubation with high glucose conditions. Under these particular conditions, CYP11B2 expression, in accordance with aldosterone secretion, was significantly increased compared to those observed in the cells cultured under standard-glucose condition. Angiotensin II receptor blocker partially inhibited this CYP11B2 induction, suggesting that there is local renin-angiotensin-aldosterone system activation under high glucose conditions. The suitable conditions for CYP11B2 induction in NRCMs culture system are now clarified: high-glucose conditions with relatively brief period of culture promote CYP11B2 expression in cardiomyocytes. The current system will help to accelerate further progress in research on cardiac tissue aldosterone synthesis.

  14. Protection against death and renal failure by renin-angiotensin system blockers in patients with diabetes and kidney disease.

    Science.gov (United States)

    Shen, Jian; Huang, Yan-Mei; Song, Xin-Nan; Hong, Xue-Zhi; Wang, Min; Ling, Wei; Zhang, Xiao-Xi; Zhao, Hai-Lu

    2016-07-01

    Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used to block the renin-angiotensin system (RAS). Yet it remains uncertain whether these drugs are equally effective and safe. Systematic reviews and meta-analyses of ACEis/ARBs in diabetes and kidney disease published in PubMed, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for clinical outcomes including all-cause mortality, end-stage renal disease (ESRD), hyperkalemia and cough. Eight meta-analyses included 2177-61,264 patients with follow-up of 6-108 months. RAS blockers reduced mortality (relative risk ratio (RR), 0.90, 95% confidence interval (CI), 0.86-0.95) without heterogeneity. The death protection was significant specifically with ACEis (RR, 0.85, 95% CI, 0.79-0.91), but not with ARBs. Protection against ESRD was homogenously evident by ARBs (RR, 0.79, 95% CI, 0.73-0.87), ACEis (RR, 0.79, 95% , 0.64-0.94), and both (RR, 0.79, 95% CI, 0.73-0.87). Significant side effects were hyperkalemia by ARBs (RR, 2.44, 95% CI, 1.13-5.26), and cough by ACEis (RR, 2.38, 95% CI, 1.75-3.22) CONCLUSIONS: In patients with diabetes and kidney disease, ACEis and ARBs are consistently protective for the development of ESRD. Use of ACEis alone additionally reduces deaths and increases the risk for cough. Use of ARBs alone increases the risk for hyperkalemia without additional benefit of death protection. © The Author(s) 2016.

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

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    Ilić Vesna

    2014-01-01

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

  16. The secretory phospholipase A2 group IIA: a missing link between inflammation, activated renin-angiotensin system, and atherogenesis?

    Directory of Open Access Journals (Sweden)

    Dimitar Divchev

    2008-06-01

    Full Text Available Dimitar Divchev, Bernhard SchiefferDepartment of Cardiology and Angiology, Medizinische Hochschule Hannover, GermanyAbstract: Inflammation, lipid peroxidation and chronic activation of the renin–angiotensin system (RAS are hallmarks of the development of atherosclerosis. Recent studies have suggested the involvement of the pro-inflammatory secretory phospholipase A2 (sPLA2-IIA in atherogenesis. This enzyme is produced by different cell types through stimulation by proinflammatory cytokines. It is detectable in the intima and in media smooth muscle cells, not only in atherosclerotic lesions but also in the very early stages of atherogenesis. sPLA2-IIA can hydrolyse the phospholipid monolayers of low density lipoproteins (LDL. Such modified LDL show increased affinity to proteoglycans. The modified particles have a greater tendency to aggregate and an enhanced ability to insert cholesterol into cells. This modification may promote macrophage LDL uptake leading to the formation of foam cells. Furthermore, sPLA2-IIA is not only a mediator for localized inflammation but may be also used as an independent predictor of adverse outcomes in patients with stable coronary artery disease or acute coronary syndromes. An interaction between activated RAS and phospholipases has been indicated by observations showing that inhibitors of sPLA2 decrease angiotensin (Ang II-induced macrophage lipid peroxidation. Meanwhile, various interactions between Ang II and oxLDL have been demonstrated suggesting a central role of sPLA2-IIA in these processes and offering a possible target for treatment. The role of sPLA2-IIA in the perpetuation of atherosclerosis appears to be the missing link between inflammation, activated RAS and lipidperoxidation.Keywords: secretory phospholipase A2, lipoproteins, renin-angiotensin system, inflammation, atherosclerosis

  17. Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling.

    Science.gov (United States)

    Hu, L W; Benvenuti, L A; Liberti, E A; Carneiro-Ramos, M S; Barreto-Chaves, M L M

    2003-12-01

    The present study assessed the possible involvement of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) in thyroxine (T4)-induced cardiac hypertrophy. Hemodynamic parameters, heart weight (HW), ratio of HW to body weight (HW/BW), and myocyte width were evaluated in absence of thyroid hormone (hypothyroidism) and after T4 administration. Male Wistar rats were used. Some were subjected to thyroidectomies, whereas hyperthyroidism was induced in others via daily intraperitoneal injection of T4 (25 or 100 microg x 100 g BW(-1) x day(-1)) for 7 days. In some cases, T4 administration was combined with the angiotensin I-converting enzyme inhibitor enalapril (Ena), with the angiotensin type 1 (AT1) receptor blocker losartan (Los) or with the beta-adrenergic blocker propanolol (Prop). Hemodynamics and morphology were then evaluated. Systolic blood pressure (SBP) was not altered by administration of either T4 alone or T4 in combination with the specific inhibitors. However, SBP decreased significantly in hypothyroid rats. An increased heart rate was seen after administration of either T4 alone or T4 in combination with either Los or Ena. Although the higher dose of T4 significantly increased HW, HW/BW increased in both T4-treated groups. Ena and Prop inhibited the increase in HW or HW/BW in hyperthyroid rats. Morphologically, both T4 dose levels significantly increased myocyte width, an occurrence prevented by RAS or SNS blockers. There was a good correlation between changes in HW/BW and myocyte width. These results indicate that T4-induced cardiac hypertrophy is associated with both the SNS and the RAS.

  18. High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion.

    Science.gov (United States)

    Li, Caixia; Culver, Silas A; Quadri, Syed; Ledford, Kelly L; Al-Share, Qusai Y; Ghadieh, Hilda E; Najjar, Sonia M; Siragy, Helmy M

    2015-11-01

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene (Cc1(-/-)) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type (Cc1(+/+)) and Cc1(-/-) mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1(-/-) mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr(508)) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1(+/+) mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1(-/-) mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr(508)) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1(-/-) mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis. Copyright © 2015 the American Physiological Society.

  19. Reduction of regurgitation in aortic insufficiency by inhibition of the renin/angiotensin conversion enzyme

    Energy Technology Data Exchange (ETDEWEB)

    Reske, S.N.; Heck, I.; Mattern, H.

    1984-10-01

    The effect of captopril-mediated afterload reduction on regurgitation was investigated in 10 patients with aortic insufficiency. Regurgitation was quantitated by the regurgitation fraction and the relation of regurgitant volume to end-diastolic volume, which were derived from gated radionuclide ventriculography. 19 patients with coronary artery disease and no evidence of valvular heart disease served as controls. In patients with coronary artery disease no significant reguration was found. In patients with aortic regurgitation the blood concentration of angiotensin I increased whereas that of angiotensin II decreased significantly after captopril-medication; thus, the conversion of angiotensin I to II was reduced to about 50% of the control value. Whereas blood pressure and heart rate did not change significantly, the regurgitation fraction and the normalized regurgitant volume were significantly reduced. The ejection fraction remained essentially unchanged. These findings suggest a favorable influence of captopril-induced afterload reduction on hemodynamics in aortic regurgitation.

  20. Radioimmunoassay for plasma renin activity

    International Nuclear Information System (INIS)

    1975-01-01

    A radioimmunoassay for the determination of renin activity in blood plasma is described. The plasma sample is mixed with a generator buffer solution also containing an inhibitor for enzymes which convert angiotensin I into other substances. The renin in the plasma sample converts angiotensinogen into angiotensin I. The amount of angiotensin I is then measured with a competitive binding method using 125 I-labelled angiotensin I and antibodies to angiotensin I

  1. Vascular endothelial growth factor during hypoglycemia in patients with type 1 diabetes mellitus: relation to cognitive function and renin-angiotensin system activity

    DEFF Research Database (Denmark)

    Kristensen, Peter Lommer; Høi-Hansen, Thomas; Boomsma, Frans

    2009-01-01

    hypoglycemia. High activity in the renin-angiotensin system (RAS) is associated with an increased risk of severe hypoglycemia in patients with type 1 diabetes mellitus. Renin-angiotensin system possibly exerts its mechanism in hypoglycemia via VEGF. We studied the impact of mild hypoglycemia on plasma VEGF...... in patients with type 1 diabetes mellitus and high or low RAS activity and analyzed associations between VEGF levels and cognitive function during hypoglycemia. Eighteen patients with type 1 diabetes mellitus-9 with high and 9 with low RAS activity-underwent a single-blinded, placebo-controlled, crossover...... study with either mild hypoglycemia or stable glycemia. Cognitive function was assessed by the California Cognitive Assessment Package and the Alzheimer Quick Test. Nadir plasma glucose was 2.2 (0.3) mmol/L. During the control study, plasma VEGF did not change. During hypoglycemia, plasma VEGF increased...

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

    Czech Academy of Sciences Publication Activity Database

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  5. Renin release

    DEFF Research Database (Denmark)

    Schweda, Frank; Friis, Ulla; Wagner, Charlotte

    2007-01-01

    in the walls of renal afferent arterioles at the entrance of the glomerular capillary network. It has been known for a long time that renin synthesis and secretion are stimulated by the sympathetic nerves and the prostaglandins and are inhibited in negative feedback loops by angiotensin II, high blood pressure...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  7. Reno-Cerebral Reflex Activates the Renin-Angiotensin System, Promoting Oxidative Stress and Renal Damage After Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Cao, Wei; Li, Aiqing; Li, Jiawen; Wu, Chunyi; Cui, Shuang; Zhou, Zhanmei; Liu, Youhua; Wilcox, Christopher S; Hou, Fan Fan

    2017-09-01

    A kidney-brain interaction has been described in acute kidney injury, but the mechanisms are uncertain. Since we recently described a reno-cerebral reflex, we tested the hypothesis that renal ischemia-reperfusion injury (IRI) activates a sympathetic reflex that interlinks the renal and cerebral renin-angiotensin axis to promote oxidative stress and progression of the injury. Bilateral ischemia-reperfusion activated the intrarenal and cerebral, but not the circulating, renin-angiotensin system (RAS), increased sympathetic activity in the kidney and the cerebral sympathetic regulatory regions, and induced brain inflammation and kidney injury. Selective renal afferent denervation with capsaicin or renal denervation significantly attenuated IRI-induced activation of central RAS and brain inflammation. Central blockade of RAS or oxidative stress by intracerebroventricular (ICV) losartan or tempol reduced the renal ischemic injury score by 65% or 58%, respectively, and selective renal afferent denervation or reduction of sympathetic tone by ICV clonidine decreased the score by 42% or 52%, respectively (all p renal damage and dysfunction persisted after controlling blood pressure with hydralazine. This study uncovered a novel reflex pathway between ischemic kidney and the brain that sustains renal oxidative stress and local RAS activation to promote ongoing renal damage. These data suggest that the renal and cerebral renin-angiotensin axes are interlinked by a reno-cerebral sympathetic reflex that is activated by ischemia-reperfusion, which contributes to ischemia-reperfusion-induced brain inflammation and worsening of the acute renal injury. Antioxid. Redox Signal. 27, 415-432.

  8. New sensitive direct radioimmunoassay for human plasma renin and its clinical application

    International Nuclear Information System (INIS)

    Higaki, J.; Ogihara, T.; Imai, N.; Kumahara, Y.; Hontani, S.; Nishiura, M.; Ogawa, H.; Hirose, S.; Murakami, K.

    1984-01-01

    A new sensitive direct radioimmunoassay for human plasma renin has been developed. Renin was purified from Haas' preparation utilizing a pepstatin-C 6 -Sepharose affinity chromatography. Antiserum, prepared by immunizing rabbits with the purified renin, was used for the direct radioimmunoassay at a final dilution of 1:30,000. The antibody was specific for human renal and plasma renin, but did not cross-react with cathepsin D, trypsin, or renins of mouse, dog, and rat. Radioimmunoassay was performed by the double antibody technique using the delayed tracer addition method. In this method, a standard curve was obtained over a range from 0.2 to 8.0 ng/ml. The values from this assay correlated well with total renin activity measured as the generation rate of angiotensin I after trypsin activation, but correlated weakly with active renin activity. This finding disclosed that both active and inactive renin were detected by this method. In normal participants, plasma renin concentration determined by direct radioimmunoassay was increased by standing and furosemide injection. The plasma renin concentration determined by direct radioimmunoassay of patients with essential hypertension was not significantly different from values in normal controls. The values were higher in patients with renovascular hypertension, malignant hypertension and Bartter's syndrome, but lower in patients with primary aldosteronism than in normal controls. 20 references, 7 figures

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

    Science.gov (United States)

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

    2017-05-08

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

  10. The Role of Vasodilator Receptors of Renin-angiotensin System on Nitric Oxide Formation and Kidney Circulation after Angiotensin II Infusion in Renal Ischemia/Reperfusion Rats.

    Science.gov (United States)

    Maleki, Maryam; Hasanshahi, Jalal; Moslemi, Fatemeh

    2018-01-01

    Nitric oxide (NO) as a vasodilator factor has renoprotective effect against renal ischemia. The balance between angiotensin II (Ang II) and NO can affect kidney homeostasis. The aim of this study was to determine NO alteration in response to renin-Ang system vasodilator receptors antagonists (PD123319; Ang II type 2 receptor antagonist and A779; Mas receptor antagonist) in renal ischemia/reperfusion injury (IRI) in rats. Sixty-three Wistar male and female rats were used. Animals from each gender were divided into four groups received saline, Ang II, PD123319 + Ang II, and A779 + Ang II after renal IRI. Renal IRI induced with an adjustable hook. Blood pressure and renal blood flow (RBF) measured continuously. The nitrite levels were measured in serum, kidney, and urine samples. In female rats, the serum and kidney nitrite levels increased significantly by Ang II ( P < 0.05) and decreased significantly ( P < 0.05) when PD123319 was accompanied with Ang II. Such observation was not seen in male. Ang II decreased RBF significantly in all groups ( P < 0.05), while PD + Ang II group showed significant decrease in RBF in comparison with the other groups in female rats ( P < 0.05). Males show more sensibility to Ang II infusion; in fact, it is suggested that there is gender dimorphism in the Ang II and NO production associated with vasodilator receptors.

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

    Science.gov (United States)

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

    2017-03-09

    Objective  To examine long term cardiorenal outcomes associated with increased concentrations of creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment. Design  Population based cohort study using electronic health records from the Clinical Practice Research Datalink and Hospital Episode Statistics. Setting  UK primary care, 1997-2014. Participants  Patients starting treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers (n=122 363). Main outcome measures  Poisson regression was used to compare rates of end stage renal disease, myocardial infarction, heart failure, and death among patients with creatinine increases of 30% or more after starting treatment against those without such increases, and for each 10% increase in creatinine. Analyses were adjusted for age, sex, calendar period, socioeconomic status, lifestyle factors, chronic kidney disease, diabetes, cardiovascular comorbidities, and use of other antihypertensive drugs and non-steroidal anti-inflammatory drugs. Results  Among the 2078 (1.7%) patients with creatinine increases of 30% or more, a higher proportion were female, were elderly, had cardiorenal comorbidity, and used non-steroidal anti-inflammatory drugs, loop diuretics, or potassium sparing diuretics. Creatinine increases of 30% or more were associated with an increased adjusted incidence rate ratio for all outcomes, compared with increases of less than 30%: 3.43 (95% confidence interval 2.40 to 4.91) for end stage renal disease, 1.46 (1.16 to 1.84) for myocardial infarction, 1.37 (1.14 to 1.65) for heart failure, and 1.84 (1.65 to 2.05) for death. The detailed categorisation of increases in creatinine concentrations (creatinine increases of less than 30% were also associated with increased incidence rate ratios for all outcomes, including death (1.15 (1.09 to 1.22) for increases of 10-19% and 1.35 (1.23 to 1.49) for increases of 20-29%, using creatinine

  12. Overexpressed cyclophilin B suppresses aldosterone-induced proximal tubular cell injury both in vitro and in vivo.

    Science.gov (United States)

    Wang, Bin; Lin, Lilu; Wang, Haidong; Guo, Honglei; Gu, Yong; Ding, Wei

    2016-10-25

    The renin-angiotensin-aldosterone system (RAAS) is overactivated in patients with chronic kidney disease. Oxidative stress and endoplasmic reticulum stress (ERS) are two major mechanisms responsible for aldosterone-induced kidney injury. Cyclophilin (CYP) B is a chaperone protein that accelerates the rate of protein folding through its peptidyl-prolyl cis-trans isomerase (PPIase) activity. We report that overexpression of wild-type CYPB attenuated aldosterone-induced oxidative stress (evidenced by reduced production of reactive oxygen species and improved mitochondrial dysfunction), ERS (indicated by reduced expression of the ERS markers glucose-regulated protein 78 [GRP78] and C/-EBP homologous protein [CHOP]), and tubular cell apoptosis in comparison with aldosterone-induced human kidney-2 (HK-2) cells. The in vivo study also yielded similar results. Hence, CYPB performs a crucial function in protecting cells against aldosterone-induced oxidative stress, ERS, and tubular cell injury via its PPIase activity.

  13. Free Fatty Acids Activate Renin-Angiotensin System in 3T3-L1 Adipocytes through Nuclear Factor-kappa B Pathway

    Directory of Open Access Journals (Sweden)

    Jia Sun

    2016-01-01

    Full Text Available The activity of a local renin-angiotensin system (RAS in the adipose tissue is closely associated with obesity-related diseases. However, the mechanism of RAS activation in adipose tissue is still unknown. In the current study, we found that palmitic acid (PA, one kind of free fatty acid, induced the activity of RAS in 3T3-L1 adipocytes. In the presence of fetuin A (Fet A, PA upregulated the expression of angiotensinogen (AGT and angiotensin type 1 receptor (AT1R and stimulated the secretion of angiotensin II (ANG II in 3T3-L1 adipocytes. Moreover, the activation of RAS in 3T3-L1 adipocytes was blocked when we blocked Toll-like receptor 4 (TLR4 signaling pathway using TAK242 or NF-κB signaling pathway using BAY117082. Together, our results have identified critical molecular mechanisms linking PA/TLR4/NF-κB signaling pathway to the activity of the local renin-angiotensin system in adipose tissue.

  14. Aldosterone breakthrough during aliskiren, valsartan, and combination (aliskiren + valsartan) therapy.

    Science.gov (United States)

    Bomback, Andrew S; Rekhtman, Yelena; Klemmer, Philip J; Canetta, Pietro A; Radhakrishnan, Jai; Appel, Gerald B

    2012-01-01

    Aldosterone levels increase in 30%-40% of patients on angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers over the long term. This "aldosterone breakthrough" may carry important clinical consequences given aldosterone's nonepithelial, pro-fibrotic actions. The renin inhibitor, aliskiren, by suppressing the renin-angiotensin-aldosterone system (RAAS) proximally, may limit breakthrough compared to conventional RAAS blockade. This open-label study (NCT01129557) randomized subjects to aliskiren 300 mg daily (A), valsartan 320 mg daily (V), or aliskiren 150 mg + valsartan 160 mg daily (A+V) for 9 months. Eligible subjects had proteinuria >300 mg/day, estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m(2), and systolic blood pressure (BP) >130 or diastolic BP >80 mm Hg. Serum and 24-hour urine aldosterone (indexed to 24-hour urine Na) were checked before initiation of therapy and at 3, 6, and 9 months. Aldosterone breakthrough was defined as a sustained increase from baseline aldosterone by study end. The study was intended to enroll 120 subjects but was terminated early by the sponsor. We present here the results of 33 subjects who completed the protocol, of which 12 were randomized to A, 11 were randomized to V, and 10 were randomized to A+V. Mean baseline eGFR was 75.5 (±23.3) mL/min/1.73 m(2); baseline proteinuria was 3104 (±2943) mg/day; and baseline BP was 134.7 (±10.5)/84.8 (±8.4) mm Hg. Three (27%) subjects on V, three (25%) subjects on A, and three (30%) subjects on A+V had aldosterone breakthrough. Mean proteinuria reduction was 31% from baseline in all subjects: 30% in subjects with breakthrough vs. 32% in subjects without breakthrough. Mean BP reduction was 11.0/8.8 mm Hg in all subjects: 8.4/6.1 mm Hg in subjects with breakthrough vs. 12.0/9.8 mm Hg in subjects without breakthrough. Aliskiren, alone or in combination with valsartan, did not reduce the incidence of aldosterone breakthrough in subjects with hypertension

  15. The effect of renin-angiotensin system blockade on renal protection in chronic kidney disease patients with hyperkalemia.

    Science.gov (United States)

    Lee, Ju-Hyun; Kwon, Young Eun; Park, Jung Tak; Lee, Mi Jung; Oh, Hyung Jung; Han, Seung Hyeok; Kang, Shin-Wook; Choi, Kyu Hun; Yoo, Tae-Hyun

    2014-12-01

    The aim of this study was to determine the effects of renin-angiotensin system (RAS) blockade maintenance on renal protection in chronic kidney disease (CKD) patients with hyperkalemia occurring during treatment with RAS blockade. CKD III or IV patients, who were prescribed with RAS blockers and also had hyperkalemia, were included. The study population was divided into two groups based on maintenance or withdrawal of RAS blocker. Renal outcomes (doubling of creatinine or end-stage renal disease) and incidence of hyperkalemia were compared between the two groups. Out of 258 subjects who developed hyperkalemia during treatment with RAS blockers, 150 (58.1%) patients continued on RAS blockades, while RAS blockades were discontinued for more than 3 months in the remaining 108 patients. Renal event-free survival was significantly higher in the maintenance group compared with the withdrawal group. Cox proportional hazard ratio for renal outcomes was 1.35 (95% CI: 1.08-1.92, p=0.04) in the withdrawal group compared with the maintenance group. However, the incidence of hyperkalemia and hyperkalemia-related hospitalization or mortality did not differ between the two groups. This study demonstrated that the maintenance of RAS blockade is beneficial for the preservation of renal function and relatively tolerable in patients with CKD and hyperkalemia occurring during treatment with RAS blockade. © The Author(s) 2014.

  16. High fat diet exacerbates neuroinflammation in an animal model of multiple sclerosis by activation of the Renin Angiotensin system.

    Science.gov (United States)

    Timmermans, Silke; Bogie, Jeroen F J; Vanmierlo, Tim; Lütjohann, Dieter; Stinissen, Piet; Hellings, Niels; Hendriks, Jerome J A

    2014-03-01

    Epidemiological studies suggest a positive correlation between the incidence and severity of multiple sclerosis (MS) and the intake of fatty acids. It remains to be clarified whether high fat diet (HFD) indeed can exacerbate the disease pathology associated with MS and what the underlying mechanisms are. In this study, we determined the influence of HFD on the severity and pathology of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Mice were fed either normal diet (ND) or HFD and subsequently induced with EAE. Immunohistochemical staining and real-time PCR were used to determine immune cell infiltration and inflammatory mediators in the central nervous system (CNS). Our data show that HFD increases immune cell infiltration and inflammatory mediator production in the CNS and thereby aggravates EAE. Moreover, our data demonstrate that activation of the renin angiotensin system (RAS) is associated with the HFD-mediated effects on EAE severity. These results show that HFD exacerbates an autoreactive immune response within the CNS. This indicates that diets containing excess fat have a significant influence on neuroinflammation in EAE, which may have important implications for the treatment and prevention of neuroinflammatory disorders.

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

    Directory of Open Access Journals (Sweden)

    Xia Zou

    2015-01-01

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

  18. Role of the renin-angiotensin system, renal sympathetic nerve system, and oxidative stress in chronic foot shock-induced hypertension in rats.

    Science.gov (United States)

    Dong, Tao; Chen, Jing-Wei; Tian, Li-Li; Wang, Lin-Hui; Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Zhao, Xiao-Dong; Zhu, Wei; Wang, Guo-Qing; Sun, Wan-Ping; Zhang, Guo-Xing

    2015-01-01

    The renin-angiotensin system (RAS) and renal sympathetic nerve system (RSNS) are involved in the development of hypertension. The present study is designed to explore the possible roles of the RAS and the RSNS in foot shock-induced hypertension. Male Sprague-Dawley rats were divided into six groups: control, foot shock, RSNS denervation, denervation plus foot shock, Captopril (angiotensin I converting enzyme inhibitor, ACE inhibitor) plus foot shock, and Tempol (superoxide dismutase mimetic) plus foot shock. Rats received foot shock for 14 days. We measured the quantity of thiobarbituric acid reactive substances (TBARS), corticosterone, renin, and angiotensin II (Ang II) in plasma, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and renal noradrenaline content. RAS component mRNA and protein levels were quantified in the cerebral cortex and hypothalamus. The two week foot shock treatment significantly increased systolic blood pressure, which was accompanied by an increase in angiotensinogen, renin, ACE1, and AT1a mRNA and protein expression in the cerebral cortex and hypothalamus, an increase of the plasma concentrations of renin, Ang II, corticosterone, and TBARS, as well as a decrease in plasma SOD and GSH-Px activities. Systolic blood pressure increase was suppressed by denervation of the RSNS or treatment with Captopril or Tempol. Interestingly, denervation or Tempol treatment both decreased main RAS components not only in the circulatory system, but also in the central nervous system. In addition, decreased antioxidant levels and increased TBARS and corticosterone levels were also partially restored by denervation or treatment with Tempol or Captopril. RAS, RSNS and oxidative stress reciprocally potentiate to play important roles in the development of foot shock-induced hypertension.

  19. Effects of exercise training on circulating and skeletal muscle renin-angiotensin system in chronic heart failure rats.

    Science.gov (United States)

    Gomes-Santos, Igor Lucas; Fernandes, Tiago; Couto, Gisele Kruger; Ferreira-Filho, Julio César Ayres; Salemi, Vera Maria Cury; Fernandes, Fernanda Barrinha; Casarini, Dulce Elena; Brum, Patricia Chakur; Rossoni, Luciana Venturini; de Oliveira, Edilamar Menezes; Negrao, Carlos Eduardo

    2014-01-01

    Accumulated evidence shows that the ACE-AngII-AT1 axis of the renin-angiotensin system (RAS) is markedly activated in chronic heart failure (CHF). Recent studies provide information that Angiotensin (Ang)-(1-7), a metabolite of AngII, counteracts the effects of AngII. However, this balance between AngII and Ang-(1-7) is still little understood in CHF. We investigated the effects of exercise training on circulating and skeletal muscle RAS in the ischemic model of CHF. Male Wistar rats underwent left coronary artery ligation or a Sham operation. They were divided into four groups: 1) Sedentary Sham (Sham-S), 2) exercise-trained Sham (Sham-Ex), sedentary CHF (CHF-S), and exercise-trained CHF (CHF-Ex). Angiotensin concentrations and ACE and ACE2 activity in the circulation and skeletal muscle (soleus and plantaris) were quantified. Skeletal muscle ACE and ACE2 protein expression, and AT1, AT2, and Mas receptor gene expression were also evaluated. CHF reduced ACE2 serum activity. Exercise training restored ACE2 and reduced ACE activity in CHF. Exercise training reduced plasma AngII concentration in both Sham and CHF rats and increased the Ang-(1-7)/AngII ratio in CHF rats. CHF and exercise training did not change skeletal muscle ACE and ACE2 activity and protein expression. CHF increased AngII levels in both soleus and plantaris muscle, and exercise training normalized them. Exercise training increased Ang-(1-7) in the plantaris muscle of CHF rats. The AT1 receptor was only increased in the soleus muscle of CHF rats, and exercise training normalized it. Exercise training increased the expression of the Mas receptor in the soleus muscle of both exercise-trained groups, and normalized it in plantaris muscle. Exercise training causes a shift in RAS towards the Ang-(1-7)-Mas axis in skeletal muscle, which can be influenced by skeletal muscle metabolic characteristics. The changes in RAS circulation do not necessarily reflect the changes occurring in the RAS of skeletal

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

    Directory of Open Access Journals (Sweden)

    Diego Lopes Mendes Barretti

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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    The role for ANG II in renal blood flow (RBF) autoregulation is unsettled. The present study was designed to test the effect of clamping plasma ANG II concentrations ([ANG II]) by simultaneous infusion of the angiotensin-converting enzyme inhibitor captopril and ANG II on RBF autoregulation...... in halothane-anesthetized Sprague-Dawley rats. Autoregulation was defined as the RBF response to acute changes in renal perfusion pressure (RPP). Regulation was defined as changes in RBF during long-lasting changes in RPP. The results showed that a prolonged reduction of RPP reset the lower limit...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Graziela S Ceravolo

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

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

    Science.gov (United States)

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

    2014-07-01

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

  5. Elevated N-terminal pro-brain natriuretic peptide levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of dietary sodium restriction and diuretics, but not angiotensin receptor blockade, in proteinuric renal patients

    NARCIS (Netherlands)

    Slagman, Maartje C. J.; Waanders, Femke; Vogt, Liffert; Damman, Kevin; Hemmelder, Marc; Navis, Gerjan; Laverman, Gozewijn D.

    Background. Renin angiotensin aldosterone system (RAAS) blockade only partly reduces blood pressure, proteinuria and renal and cardiovascular risk in chronic kidney disease (CKD) but often requires sodium targeting [i.e. low sodium diet (LS) and/or diuretics] for optimal efficacy. However, both

  6. Elevated N-terminal pro-brain natriuretic peptide levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of dietary sodium restriction and diuretics, but not angiotensin receptor blockade, in proteinuric renal patients

    NARCIS (Netherlands)

    Slagman, Maartje C. J.; Waanders, Femke; Vogt, Liffert; Damman, Kevin; Hemmelder, Marc; Navis, Gerjan; Laverman, Gozewijn D.

    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

  7. Living high training low induces physiological cardiac hypertrophy accompanied by down-regulation and redistribution of the renin-angiotensin system

    Science.gov (United States)

    Shi, Wei; Meszaros, J Gary; Zeng, Shao-ju; Sun, Ying-yu; Zuo, Ming-xue

    2013-01-01

    Aim: Living high training low” (LHTL) is an exercise-training protocol that refers living in hypoxia stress and training at normal level of O2. In this study, we investigated whether LHTL caused physiological heart hypertrophy accompanied by changes of biomarkers in renin-angiotensin system in rats. Methods: Adult male SD rats were randomly assigned into 4 groups, and trained on living low-sedentary (LLS, control), living low-training low (LLTL), living high-sedentary (LHS) and living high-training low (LHTL) protocols, respectively, for 4 weeks. Hematological parameters, hemodynamic measurement, heart hypertrophy and plasma angiotensin II (Ang II) level of the rats were measured. The gene and protein expression of angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II receptor I (AT1) in heart tissue was assessed using RT-PCR and immunohistochemistry, respectively. Results: LLTL, LHS and LHTL significantly improved cardiac function, increased hemoglobin concentration and RBC. At the molecular level, LLTL, LHS and LHTL significantly decreased the expression of ACE, AGT and AT1 genes, but increased the expression of ACE and AT1 proteins in heart tissue. Moreover, ACE and AT1 protein expression was significantly increased in the endocardium, but unchanged in the epicardium. Conclusion: LHTL training protocol suppresses ACE, AGT and AT1 gene expression in heart tissue, but increases ACE and AT1 protein expression specifically in the endocardium, suggesting that the physiological heart hypertrophy induced by LHTL is regulated by region-specific expression of renin-angiotensin system components. PMID:23377552

  8. Effector peptides of the renin-angiotensin system in the central mechanisms of acquired and innate behavior in thirst in rats.

    Science.gov (United States)

    Vlasenko, R Ya; Kotov, A V

    2007-03-01

    We report here a comparative analysis of the involvement of a number of components of the renin-angiotensin system in the performance of simple and complex forms of drinking behavior and thirst-associated non-drinking types of behavior. On central (intracerebroventricular) microinjection, [des-Asp1]-angiotensin I at doses equieffective to those of angiotensins II and III was found to be involved only in the performance of simple (taking water from the bowl) and linked forms of activity (comfort behavior, stress grooming, orientational-investigative, and feeding behavior). Angiotensin II was involved in the central mechanisms of complex acquired drinking behavior, selectively modulating its key stages (initial, final), while angiotensin III was involved only in the mechanisms of reproduction of the complex skill. All three substances induced "innate patterns of behavior" specific for each compound, these occurring at fixed periods of time after intracerebral microinjection. The effects of these substances were selectively suppressed by the AT1 receptor blocker losartan potassium.

  9. Increased Aldosterone Release During Head-Up Tilt in Early Primary Hypertension.

    Science.gov (United States)

    Reinold, Annemarie; Schneider, Andreas; Kalizki, Tatjana; Raff, Ulrike; Schneider, Markus P; Schmieder, Roland E; Schmidt, Bernhard M W

    2017-05-01

    Hyperaldosteronism is well known cause of secondary hypertension. However, the importance of aldosterone for the much larger group of patients with primary hypertension is less clear. We hypothesized that in young subjects with primary hypertension, the rise of plasma aldosterone levels in response to head-up tilt testing as a stress stimulus is exaggerated. Hemodynamics (blood pressure (BP), heart rate (HR), cardiac index (CI), and total peripheral vascular resistance index (TPRI), all by TaskForce monitor) and hormones (plasma renin activity (PRA), angiotensin II (Ang II), aldosterone) were measured before and during 30 minutes of head-up tilt in 45 young hypertensive and 45 normotensive subjects. BP, HR, CI, and TPRI all increased in response to head-up tilt, with no difference between groups. There was no difference in baseline PRA, Ang II, and aldosterone between groups. During head-up tilt, PRA, and Ang II levels increased similarly. However, aldosterone levels increased to a greater extent in the hypertensive vs. normotensive subjects (P = 0.0021). Our data suggest that an increased release of aldosterone in response to orthostatic stress is a feature of early primary hypertension. The similar increase in PRA and Ang II suggests a potential role for secretagogues of aldosterone other than Ang II in this response. In addition to its established role in secondary hypertension, dysregulation of aldosterone release might contribute to the development of primary arterial hypertension. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  10. Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Tekatas, Demet D; Bahcecioglu, Ibrahim H; Ispiroglu, Murat; Sahin, Abdurrahman; Ilhan, Necip; Yalniz, Mehmet; Demirel, Ulvi

    2016-01-01

    In this study, we aimed to investigate the histological and clinical effect of angiotensin-converting enzyme (ACE) and ACE gene polymorphism in nonalcoholic fatty liver disease (NAFLD) and their roles in the progression of the disease. Liver function tests, body mass index, waist circumference, lipid parameters, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), homeostasis model assessment-IR (HOMA-IR), ACE, and ACE gene polymorphism were evaluated in the NAFLD group and control group. The study group was evaluated by dividing the group into four subgroups by ACE gene polymorphism (D/D homozygous, I/I homozygous, D/I heterozygous, I/D heterozygous). Liver biopsies were evaluated according to Brunt Classification. A total of 31 patients who were diagnosed with NAFLD and 40 healthy individuals were included in the study. The ACE level was found to be 11.69 ± 1.99 in the NAFLD group and 11.52 ± 1.72 in the control group (p = 0.70). There was a negative correlation between ACE levels and HOMA-IR levels (p = 0.008, r= -0.512). Biochemical parameters were not different among ACE gene polimorphism subgroups, except FBG (between D/D, I/D and D/I, I/D; p = 0.02). When the ACE levels were compared in terms of grade and stage, no significant difference was found (for stage and grade p = 0.68). The ACE gene polymorphism subgroups did not differ by histopathologic findings; grade and stage (for grade p = 0.42, for stage p = 0.92). In this study, we could not find a correlation of ACE and ACE gene polymorphism with metabolic risk factors and the disease severity in NAFLD. Tekatas DD, Bahcecioglu IH, Ispiroglu M, Sahin A, Ilhan N, Yalniz M, Demirel U. Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(2):137-142.

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

    Directory of Open Access Journals (Sweden)

    Eliete Dalla Corte Frantz

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

  12. Interaction between sympathetic nervous system and renin angiotensin system on MMPs expression in juvenile rat aorta.

    Science.gov (United States)

    Dab, Houcine; Hachani, Rafik; Hodroj, Wassim; Sakly, Mohsen; Bricca, Giampiero; Kacem, Kamel

    2011-09-01

    The aim of our present study is to investigate the interaction between angiotensin II (ANG II) and sympathetic nervous system (SNS) on matrix metalloproteinase MMP-2 and MMP-9 expression and activity in juvenile rat aorta under normal conditions. Sympathectomy with guanethidine and blockade of the ANG II receptors (AT1R) by losartan were performed alone or in combination on new-born rats. mRNA, protein expression and activity of MMP-2 and MMP-9 were examined by Q-RT-PCR, immunoblotting and zymography, respectively. MMP-2 mRNA and protein amount were decreased after sympathectomy or AT1R blockade and an additive effect was observed after combined treatment. However, MMP-9 expression was reduced to the same level in the three treated groups. There were some detectable gelatinolytic activity of the MMPs in both control and treated rats. We concluded that ANG II stimulates directly and indirectly (via sympathostimulator pathway) the MMP-2 expression but seems unable to affect MMP-9 expression through direct pathway. Combined inhibition of SNS and ANG II were more efficient than a single inhibition in reducing MMP amounts in rat vessels.

  13. Interactions of renin-angiotensin system gene polymorphisms and antihypertensive effect of benazepril in Chinese population.

    Science.gov (United States)

    Chen, Qing; Yu, Can-Qing; Tang, Xun; Chen, Da-Fang; Tian, Jun; Cao, Yang; Fan, Wen-Yi; Cao, Wei-Hua; Zhan, Si-Yan; Lv, Jun; Guo, Xiao-Xia; Hu, Yong-Hua; Lee, Li-Ming

    2011-05-01

    Angiotensin-converting enzyme inhibitors are widely used antihypertensive drugs with individual response variation. We studied whether interactions of AGT, AGTR1 and ACE2 gene polymorphisms affect this response. Our study is based on a 3-year field trial with 1831 hypertensive patients prescribed benazepril. Generalized multifactor dimensionality reduction was used to explore interaction models and logistic regressions were used to confirm them. A two-locus model involving the AGT and ACE2 genes was found in males, the sensitive genotypes showed an odds ratio (OR) of 1.9 (95% CI: 1.3-2.8) when compared with nonsensitive genotypes. Two AGT-AGTR1 models were found in females, with an OR of 3.5 (95% CI: 2.0-5.9) and 3.1 (95% CI: 1.8-5.3). Gender-specific gene-gene interactions of the AGT, AGTR1 and ACE2 genes were associated with individual variation of response to benazepril. Further studies are needed to confirm this finding.

  14. Shifts in renin-angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice.

    Science.gov (United States)

    Qian, Xiaobing; Lin, Leilei; Zong, Yao; Yuan, Yongguang; Dong, Yanmin; Fu, Yue; Shao, Wanwen; Li, Yujie; Gao, Qianying

    2018-03-01

    This study aimed to analyse shifts in renin-angiotensin system (RAS) components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa (LC) region in streptozotocin (STZ)-induced diabetic mice. Six months after diabetes induction, the retinal vessels of male C57BL/6 J mice were observed by colour photography, fundus fluorescein angiography (FFA), and immunofluorescent staining following incubation with CD31. Immunofluorescence for glial fibrillary acidic protein (GFAP), alpha-smooth muscle actin (α-SMA),and NG2 was also performed. Angiotensin-converting enzyme 1 (ACE1), angiotensin II type I receptor (AT1R), renin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and haeme oxygenase 1 (HO-1) expression levels were confirmed by immunohistochemical and western blotting analyses. Compared with control mice, diabetic mice had significantly higher blood glucose concentrations (p diabetic mice; however, immunostaining of whole-mount retinas revealed an increased number of retinal vessels. Furthermore, histopathological staining showed significant reduction in the whole retinal thickness. GFAP expression was slightly higher, whereas fewer NG2 + pericytes were observed in diabetic mice than in control mice. ACE1, AT1R, renin, HIF-1α, VEGF, VEGFR2, and HO-1 expression were up-regulated in the LC of the STZ-induced diabetic mice. Collectively, ACE 1, AT1R, HIF-1α, VEGF, VEGFR2, and HO-1 activation in the LC region in diabetic mice may be involved in diabetes via the RAS and induction of angiogenesis and oxidative stress.

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

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

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

  16. Menopause not aldosterone-to-renin ratio predicts blood pressure response to a mineralocorticoid receptor antagonist in primary care hypertensive patients.

    Science.gov (United States)

    Olivieri, Oliviero; Pizzolo, Francesca; Ciacciarelli, Alberto; Corrocher, Roberto; Signorelli, Denise; Falcone, Salvatore; Blengio, Gian S

    2008-09-01

    It has been suggested that hypertensive patients with raised aldosterone-to-renin ratio (ARR) are specifically sensitive to mineralocorticoid receptor antagonists (MRAs). We have previously shown that patients with an elevated ARR are relatively frequent in the setting of primary care. We therefore designed an interventional study to ascertain whether primary care hypertensive patients with an elevated ARR presented a superior response to MRA treatment than subjects with normal ratio. According to the previously observed distribution in general population, 1/3 and 2/3 of hypertensive patients with high or normal ARR, respectively, were treated with kanrenoate 50-100 mg/day for 2 months. To avoid uncontrolled blood pressure (BP), 49% of patients continued also "ARR-neutral" drugs such as verapamil and/or alpha-adrenergic blockers. Patients groups were matched for most features but an elevated ARR was more frequent in female than in male gender; moreover, 90% of women with raised ARR were in menopause. A clear reduction of BP values was recorded after both the first and the second month of treatment with kanrenoate, with the maximal effect obtained when the dosage titration at 100 mg/day was accomplished. However, patients previously identified by a raised ARR did not have a larger response to MRA treatment than patients with normal ratio. In contrast, MRA was twofold more effective in reducing SBP in women than in men (after 2 months of treatment -16.4 mm Hg vs.-8.2 mm Hg). These results suggest that postmenopausal hypertension is largely dependent on mineralocorticoid receptor activation and selectively sensitive to MRAs.

  17. Acute change in glomerular filtration rate with inhibition of the renin-angiotensin system does not predict subsequent renal and cardiovascular outcomes.

    Science.gov (United States)

    Clase, Catherine M; Barzilay, Joshua; Gao, Peggy; Smyth, Andrew; Schmieder, Roland E; Tobe, Sheldon; Teo, Koon K; Yusuf, Salim; Mann, Johannes F E

    2017-03-01

    Initiation of blockade of the renin-angiotensin system may cause an acute decrease in glomerular filtration rate (GFR): the prognostic significance of this is unknown. We did a post hoc analysis of patients with, or at risk for, vascular disease, in two randomized controlled trials: Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACE iNtolerant participants with cardiovascular Disease (TRANSCEND), whose median follow-up was 56 months. In 9340 patients new to renin-angiotensin system blockade, who were then randomized to renin-angiotensin system blockade, a fall in GFR of 15% or more at 2 weeks after starting renin-angiotensin system blockade was seen in 1480 participants (16%), with persistence at 8 weeks in 700 (7%). Both acute increases and decreases in GFR after initiation of renin-angiotensin system blockade were associated with tendencies, mostly not statistically significant, to increased risk of cardiovascular outcomes, which occurred in 1280 participants, and of microalbuminuria, which occurred in 864. Analyses of creatinine-based outcomes were suggestive of regression to the mean. In more than 3000 patients randomized in TRANSCEND to telmisartan or placebo, there was no interaction between acute change in GFR and renal or cardiovascular benefit from telmisartan. Thus, both increases and decreases in GFR on initiation of renin-angiotensin system blockade are common, and may be weakly associated with increased risk of cardiovascular and renal outcomes. Changes do not predict increased benefit from therapy. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  18. Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling.

    Science.gov (United States)

    Resch, Jon M; Fenselau, Henning; Madara, Joseph C; Wu, Chen; Campbell, John N; Lyubetskaya, Anna; Dawes, Brian A; Tsai, Linus T; Li, Monica M; Livneh, Yoav; Ke, Qingen; Kang, Peter M; Fejes-Tóth, Géza; Náray-Fejes-Tóth, Anikó; Geerling, Joel C; Lowell, Bradford B

    2017-09-27

    Sodium deficiency increases angiotensin II (ATII) and aldosterone, which synergistically stimulate sodium retention and consumption. Recently, ATII-responsive neurons in the subfornical organ (SFO) and aldosterone-sensitive neurons in the nucleus of the solitary tract (NTS HSD2 neurons) were shown to drive sodium appetite. Here we investigate the basis for NTS HSD2 neuron activation, identify the circuit by which NTS HSD2 neurons drive appetite, and uncover an interaction between the NTS HSD2 circuit and ATII signaling. NTS HSD2 neurons respond to sodium deficiency with spontaneous pacemaker-like activity-the consequence of "cardiac" HCN and Na v 1.5 channels. Remarkably, NTS HSD2 neurons are necessary for sodium appetite, and with concurrent ATII signaling their activity is sufficient to produce rapid consumption. Importantly, NTS HSD2 neurons stimulate appetite via projections to the vlBNST, which is also the effector site for ATII-responsive SFO neurons. The interaction between angiotensin signaling and NTS HSD2 neurons provides a neuronal context for the long-standing "synergy hypothesis" of sodium appetite regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 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

  20. Body mass index predicts aldosterone production in normotensive adults on a high-salt diet.

    Science.gov (United States)

    Bentley-Lewis, Rhonda; Adler, Gail K; Perlstein, Todd; Seely, Ellen W; Hopkins, Paul N; Williams, Gordon H; Garg, Rajesh

    2007-11-01

    The mechanisms underlying obesity-mediated cardiovascular disease are not fully understood. Aldosterone and insulin resistance both are associated with obesity and cardiovascular disease. The objectives of this study were to test the hypotheses that aldosterone production is elevated and associated with insulin resistance in overweight adults on a high-sodium diet. Healthy normotensive adults were categorized as lean body mass index (BMI) less than 25 kg/m(2) (n = 63) or overweight BMI 25 kg/m(2) or greater (n = 57). After 7 d of a high-sodium diet, participants fasted overnight and remained supine throughout hemodynamic and laboratory assessments and angiotensin II (AngII) stimulation. The overweight group, compared with the lean group, had higher 24-h urinary aldosterone (9.0 +/- 0.8 vs. 6.6 +/- 0.5 microg per 24 h; P = 0.003) and higher AngII-stimulated serum aldosterone (11.4 +/- 1.0 vs. 9.0 +/- 0.6 ng/dl; P = 0.04). There were no differences in 24-h urinary cortisol or sodium or supine measurements of plasma renin activity, serum aldosterone, or serum potassium. The homeostasis model assessment of insulin resistance was predicted by urinary aldosterone excretion (r = 0.32, P = 0.03) and serum aldosterone response to AngII stimulation (r = 0.28, P = 0.02) independent of age and BMI. Urinary aldosterone excretion and AngII-stimulated aldosterone are increased in overweight, compared with lean, normotensive adults. The correlation of these measures of aldosterone production with insulin resistance suggests a potential role for aldosterone in the pathophysiology of obesity-mediated insulin resistance.

  1. Evaluation of aldosterone-and cortisol levels in blood plasma in normal conditions of ingestion of sodium and potassium, after saline-increase and depletion, in regard to position, and after stimulation with ACTH and angiotensin II

    International Nuclear Information System (INIS)

    Okada, H.

    1979-01-01

    Methods for the determination of plasma aldosterone and cortisol, by radioimmunoassay, were performed utilizing highly specific antisera. With this methodology it was possible to evaluate cortisol and aldosterone secretion, in six normal subjects, submitted to a basal rice diet on standing and recumbent positions, the effects of exogenous cortrosyn (β1-24 ACTH) and angiotensin II and the same manoevres with progressively increased Na + content of the diet. Aldosterone basal levels decreased with the increase of Na + content in the diet. However, there were no significant differences between the relative increments observed on the recumbent position, at the three levels of sodium intake. The relative increase of plasma aldosterone after ACTH was similar for each basal level of aldosterone induced by different sodium intakes. The responsiveness of aldosterone secretion to cortrosyn and standing position was similar, with no relation to the sodium intake. The infusion of angiotensin II induced an increase in plasma aldosterone, and the relative increment in the levels of the hormone were higher with high sodium than on the rice diet. The average basal cortisol value at the different levels of sodium intake was significantly different being greater on the basal, rice diet, and there was a decrease in cortisol level after recumbency, with the theree diets. The injection of ACTH induced similar cortisol secretion with no relation to the sodium intake. The infusion of non-hypertensive doses of angiotensin II resulted in an anomalous fall in cortisol level, probably because of 'shunt' of substrates to biosynthesis with the added effect of cortisol diurnal rhythmycity. (Author) [pt

  2. Dietary calcium intake and Renin Angiotensin System polymorphisms alter the blood pressure response to aerobic exercise: a randomized control design

    Directory of Open Access Journals (Sweden)

    Tsongalis Gregory J

    2007-01-01

    Full Text Available Abstract Background Dietary calcium intake and the renin angiotensin system (RAS regulate blood pressure (BP by modulating calcium homeostasis. Despite similar BP regulatory effects, the influence of dietary calcium intake alone and combined with RAS polymorphisms on the BP response following acute aerobic exercise (i.e., postexercise hypotension has not been studied. Thus, we examined the effect of dietary calcium intake and selected RAS polymorphisms on postexercise hypotension. Methods Subjects were men (n = 50, 43.8 ± 1.3 yr with high BP (145.3 ± 1.5/85.9 ± 1.1 mm Hg. They completed three experiments: non-exercise control and two cycle bouts at 40% and 60% of maximal oxygen consumption (VO2max. Subjects provided 3 d food records on five protocol-specific occasions. Dietary calcium intake was averaged and categorized as low (1R A/C were analyzed with molecular methods. Genotypes were reduced from three to two: ACE II/ID and ACE DD; or AT1R AA and AT1R CC/AC. Repeated measure ANCOVA tested if BP differed among experiments, dietary calcium intake level and RAS polymorphisms. Results Systolic BP (SBP decreased 6 mm Hg after 40% and 60% VO2max compared to non-exercise control for 10 h with LowCa (p 2max versus non-exercise control for 10 h among ACE II/ID (6 mm Hg and AT1R AA (8 mm Hg; and by 8 mm Hg after 40% VO2max among ACE DD and AT1R CC/CA (p 2max compared to non-exercise control for 10 h (p 2max (p ≥ 0.05. Conclusion SBP decreased after exercise compared to non-exercise control among men with low but not high dietary calcium intake. Dietary calcium intake interacted with the ACE I/D and AT1R A/C polymorphisms to further modulate postexercise hypotension. Interactions among dietary calcium intake, exercise intensity and RAS polymorphisms account for some of the variability in the BP response to exercise.

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

    Science.gov (United States)

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

    2015-01-01

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

  4. Altered renal expression of angiotensin II receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats.

    Science.gov (United States)

    Schulman, Ivonne Hernandez; Zhou, Ming-Sheng; Treuer, Adriana V; Chadipiralla, Kiranmai; Hare, Joshua M; Raij, Leopoldo

    2010-01-01

    The susceptibility to fibrosis and progression of renal disease is mitigated by inhibition of the renin-angiotensin system (RAS). We hypothesized that activation of the intrarenal RAS predisposes to renal fibrosis in aging. Intrarenal expression of angiotensin II type 1 (AT(1)R), type 2 (AT(2)R), and (pro)renin receptors, ACE and ACE-2, as well as pro- and antioxidant enzymes were measured in 3-month-old (young), 14-month-old (middle-aged), and 24-month-old (old) male Sprague-Dawley rats. Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT(1)R /AT(2)R ratios were increased in middle-aged (cortical 1.6-fold, medullary 5-fold) and old rats (cortical 2-fold, medullary 4-fold). Similarly, (pro)renin receptor expression was increased in middle-aged (cortical 2-fold, medullary 3-fold) and old (cortical 5-fold, medullary 3-fold) rats. Cortical ACE was increased (+35%) in old rats, whereas ACE-2 was decreased (-50%) in middle-aged and old rats. NADPH oxidase activity was increased (2-fold), whereas antioxidant capacity and expression of the mitochondrial enzyme manganese superoxide dismutase (cortical -40%, medullary -53%) and medullary endothelial nitric oxide synthase (-48%) were decreased in old rats. Age-related intrarenal activation of the RAS preceded the development of severe renal fibrosis, suggesting that it contributes to the increased susceptibility to renal injury observed in the elderly. Copyright © 2010 S. Karger AG, Basel.

  5. Expression of renin-angiotensin system signalling compounds in maternal protein-restricted rats: effect on renal sodium excretion and blood pressure.

    Science.gov (United States)

    Mesquita, Flávia Fernandes; Gontijo, José Antonio Rocha; Boer, Patrícia Aline

    2010-02-01

    Intrauterine growth restriction due to low maternal dietary protein during pregnancy is associated with retardation of foetal growth, renal alterations and adult hypertension. The renin-angiotensin system (RAS) is a coordinated hormonal cascade in the control of cardiovascular, renal and adrenal function that governs body fluid and electrolyte balance, as well as arterial pressure. In the kidney, all the components of the renin-angiotensin system including angiotensin II type 1 (AT1) and type 2 (AT2) receptors are expressed locally during nephrogenesis. Hence, we investigated whether low protein diet intake during pregnancy altered kidney and adrenal expression of AT1(R) and AT2(R) receptors, their pathways and if the modified expression of the RAS compounds occurs associated with changes in urinary sodium and in arterial blood pressure in sixteen-week-old males' offspring of the underfed group. The pregnancy dams were divided in two groups: with normal protein diet (pups named NP) (17% protein) or low protein diet (pups LP) (6% protein) during all pregnancy. The present data confirm a significant enhancement in arterial pressure in the LP group. Furthermore, the study showed a significantly decreased expression of RAS pathway protein and Ang II receptors in the kidney and an increased expression in the adrenal of LP rats. The detailed immunohistochemical analysis of RAS signalling proteins in the kidney confirm the immunoblotting results for both groups. The present investigation also showed a pronounced decrease in fractional urinary sodium excretion in maternal protein-restricted offspring, compared with the NP age-matched group. This occurred despite unchanged creatinine clearance. The current data led us to hypothesize that foetal undernutrition could be associated with decreased kidney expression of AT(R) resulting in the inability of renal tubules to handle the hydro-electrolyte balance, consequently causing arterial hypertension.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Guoxing Wang

    2015-11-01

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

  8. Radioimmunoassay of aldosterone in ascitic fluid

    Energy Technology Data Exchange (ETDEWEB)

    Maleeva, A; Kekhajova, M [Nauchno-Izsledovatelski Inst. po Radiologiya i Radiatsionna Khigiena, Sofia (Bulgaria)

    1988-01-01

    A method was developed dor determination of aldosterone in ascitic fluid. Elevated aldosterone levels in plasma and ascitic fluid of 10 patients with advanced cirrhosis of the liver were recorded, as compared to the plasma levels in normal subjects. Elevated aldosterone levels in these patients was of definite importance for the choice of adequate diuretic drug, since the effectiveness of diuretic treatment largely depended on renin activity and aldosterone level.

  9. Radioimmunoassay of aldosterone in ascitic fluid

    International Nuclear Information System (INIS)

    Maleeva, A.; Kekhajova, M.

    1988-01-01

    A method was developed dor determination of aldosterone in ascitic fluid. Elevated aldosterone levels in plasma and ascitic fluid of 10 patients with advanced cirrhosis of the liver were recorded, as compared to the plasma levels in normal subjects. Elevated aldosterone levels in these patients was of definite importance for the choice of adequate diuretic drug, since the effectiveness of diuretic treatment largely depended on renin activity and aldosterone level

  10. Plasma Renin Activity in Diabetes Mellitus

    International Nuclear Information System (INIS)

    Pyo, Heui Jung; Park Jung Sik; Kim, Sung Kwon; Choi, Kang Won; Lee, Jung Sang; Lee, Mun Ho

    1979-01-01

    To evaluate the renin-angiotensin-aldosterone system in diabetes mellitus, basal plasma renin activity (PRA) and its response to intravenous furosemide were determined in 40 diabetic subjects. The diabetics were divided into 4 groups according to the presence of nephropathy and/or hypertension. Uncomplicated diabetics (Group I) were taken as control group and the results of the other groups were compared to this group. In diabetics with nephropathy alone (Group II), and with nephropathy and hypertension (Group III), basal PRA values were 0.63±0.59 ng/ml/hr., and 0.79±0.62 ng/ml/hr., respectively, both significantly lower than control group. (1.53±1.09 ng/ml/hr.). (p<0.05) In both of the above groups, the responses to intravenous furosemide tended to be blunted. On the other hand, in diabetics, with hypertension only (Group IV), the basal and stimulated PRA were not significantly different from control. Above results suggests that nephropathy may be one of the factors which suppress renin activity in diabetes mellitus

  11. Plasma Renin Activity in Diabetes Mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Pyo, Heui Jung; Sik, Park Jung; Kim, Sung Kwon; Choi, Kang Won; Lee, Jung Sang; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    To evaluate the renin-angiotensin-aldosterone system in diabetes mellitus, basal plasma renin activity (PRA) and its response to intravenous furosemide were determined in 40 diabetic subjects. The diabetics were divided into 4 groups according to the presence of nephropathy and/or hypertension. Uncomplicated diabetics (Group I) were taken as control group and the results of the other groups were compared to this group. In diabetics with nephropathy alone (Group II), and with nephropathy and hypertension (Group III), basal PRA values were 0.63+-0.59 ng/ml/hr., and 0.79+-0.62 ng/ml/hr., respectively, both significantly lower than control group. (1.53+-1.09 ng/ml/hr.). (p<0.05) In both of the above groups, the responses to intravenous furosemide tended to be blunted. On the other hand, in diabetics, with hypertension only (Group IV), the basal and stimulated PRA were not significantly different from control. Above results suggests that nephropathy may be one of the factors which suppress renin activity in diabetes mellitus

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    in cerebral activity during hypoglycaemia and cognitive testing in two groups of healthy men with different basal RAS activity. METHODS: Ten healthy men with high RAS activity and 10 with low activity underwent six oxygen-15-labelled water positron emission tomography scans: twice during normoglycaemia, twice......INTRODUCTION: High renin-angiotensin system (RAS) activity has been associated with a high risk of severe hypoglycaemia in patients with type 1 diabetes and with cognitive deterioration during experimental hypoglycaemia in healthy subjects. The aim of this study was to describe possible differences...... during insulin-induced hypoglycaemia and twice during post-hypoglycaemia. During the scans, the subjects performed a computer-based reaction time test. RESULTS: Occipital areas were consistently more activated in the low RAS group than in the high RAS group throughout all three conditions. During...

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

    International Nuclear Information System (INIS)

    Nakagawa, Naoki; Yao, Naoyuki; Hirayama, Tomoya

    2011-01-01

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

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

    Science.gov (United States)

    Boshra, Vivian; Abbas, Amr M

    2017-07-26

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

  15. Involvement of skeletal renin-angiotensin system and kallikrein-kinin system in bone deteriorations of type 1 diabetic mice with estrogen deficiency.

    Science.gov (United States)

    Zhang, Yan; Wang, Liang; Liu, Jin-Xin; Wang, Xin-Luan; Shi, Qi; Wang, Yong-Jun

    This study was aimed to investigate the involvement of skeletal renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) in bone deteriorations of mice in response to the combination treatment of estrogen deficiency and hyperglycemia. The female C57BL/6J mice were sham-operated or ovariectomized with vehicle or streptozotocin (STZ) treatment. Two weeks later, the biochemistries in serum and urine were determined by standard colorimetric methods or ELISA. The H&E and TRAP staining were performed at the tibial proximal metaphysis. The polymerase chain reaction and immunoblotting were applied for molecular analysis on mRNA and protein expression. The mice after treating with ovariectomy and STZ showed the decreased level of serum Ca and the increased level of serum PTH and urine Ca. The H&E staining showed trabecular bone abnormalities as demonstrated by the loss, disconnection and separation of trabecular bone network as well as the loss of chondrocytes and appearance of chondrocyte cluster at growth plate of tibia. The significant increase of matured osteoclast number was shown in group with double treatments. The combination treatment significantly up-regulated mRNA expression of AGT, ACE, renin receptor, MMP-9 and CAII, and protein expression of renin, and decreased the ratio of OPG/RANKL and the expression of bradykinin receptors in bone tissue. Ovariectomy combined with STZ induction produced more detrimental actions on bone through the activation of local bone RAS and the down-regulation of bradykinin receptors, as compared to the respective single treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Tachyphylaxis of juxtaglomerular epithelioid cells to angiotensin II. Differences between the electrical membrane response and renin secretion

    DEFF Research Database (Denmark)

    Bührle, C P; Hackenthal, E; Nobiling, R

    1987-01-01

    A study has been made of desensitization of the depolarizing response to angiotensin II of juxtaglomerular epithelioid and vascular smooth muscle cells in the mouse kidney afferent arteriole, of media cells from the mesenteric artery as well as of cultured smooth muscle and mesangial cells. In all...... cell types, desensitization to this effect of angiotensin II was observed. There was no cross-desensitization between angiotensin II and other depolarizing agonists. Hence, it is concluded that this desensitization is specific, i.e. of the tachyphylaxis type. Substances interfering with receptor...... recycling, such as chloroquine and monensin, did not block the recovery of the cells from desensitization after removal of the octapeptide. Desensitization to the action of angiotensin II was also observed with respect to its vasoconstrictor effect in the isolated perfused rat kidney. In contrast...

  17. Mechanisms responsible for postmenopausal hypertension in a rat model: Roles of the renal sympathetic nervous system and the renin-angiotensin system.

    Science.gov (United States)

    Maranon, Rodrigo O; Reckelhoff, Jane F

    2016-02-01

    Hypertension in postmenopausal women is less well controlled than in age-matched men. The aging female SHR is a model of postmenopausal hypertension that is mediated in part by activation of the renin-angiotensin system (RAS) and by the renal sympathetic nervous system. In this study, the hypothesis was tested that renal denervation would lower the blood pressure in old female SHR and would attenuate the antihypertensive effects of AT1 receptor antagonism. Retired breeder female SHR were subjected to right uninephrectomy (UNX) and left renal denervation (RD) or UNX and sham, and 2 weeks later, baseline mean arterial pressure (MAP; radiotelemetry) was measured for 4 days, and then rats were treated with angiotensin (AT1) receptor antagonist, losartan (40 mg/kg/day po) for 6 days. Renal denervation reduced MAP in old females compared to sham (172 ± 6 vs. 193 ± 6 mm Hg; P renal sympathetic nervous system and the RAS have independent effects to control the blood pressure in old female SHR. Since the denervated rats treated with losartan remained hypertensive, the data also suggest that other mechanisms than the RAS and renal sympathetic nervous system contribute to the hypertension in old female SHR. The data also suggest that multiple mechanisms may mediate the elevated blood pressure in postmenopausal women. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  18. Renin-angiotensin system inhibition ameliorates CCl4-induced liver fibrosis in mice through the inactivation of nuclear transcription factor kappa B.

    Science.gov (United States)

    Saber, Sameh; Mahmoud, Amr A A; Helal, Noha S; El-Ahwany, Eman; Abdelghany, Rasha H

    2018-06-01

    Therapeutic interventions for liver fibrosis are still limited due to the complicated molecular pathogenesis. Renin-angiotensin system (RAS) seems to contribute to the development of hepatic fibrosis. Therefore, we aimed to examine the effect of RAS inhibition on CCl 4 -induced liver fibrosis. Mice were treated with silymarin (30 mg·kg -1 ), perindopril (1 mg·kg -1 ), fosinopril (2 mg·kg -1 ), or losartan (10 mg·kg -1 ). The administration of RAS inhibitors improved liver histology and decreased protein expression of alpha smooth muscle actin (α-SMA) and hepatic content of hydroxyproline. These effects found to be mediated via inactivation of nuclear transcription factor kappa B (NFκB) pathway by the inhibition of NFκB p65 phosphorylation at the Ser536 residue and phosphorylation-induced degradation of nuclear factor kappa-B inhibitor alpha (NFκBia) subsequently inhibited NFκB-induced TNF-α and TGF-β1, leading to lower levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF). We concluded that the tissue affinity of the angiotensin converting enzyme inhibitors (ACEIs) has no impact on its antifibrotic activity and that interfering the RAS either through the inhibition of ACE or the blockade of AT1R has the same therapeutic benefit. These results suggest RAS inhibitors as promising candidates for further clinical trials in the management of hepatic fibrosis.

  19. Recent Advances in the Gastric Mucosal Protection Against Stress-induced Gastric Lesions. Importance of Renin-angiotensin Vasoactive Metabolites, Gaseous Mediators and Appetite Peptides.

    Science.gov (United States)

    Brzozowski, Tomasz; Magierowska, Katarzyna; Magierowski, Marcin; Ptak-Belowska, Agata; Pajdo, Robert; Kwiecien, Slawomir; Olszanecki, Rafal; Korbut, Ryszard

    2017-01-01

    Stress is known to cause severe adverse effects in the human gastrointestinal tract including mucosal microbleedings and erosions or even gastric ulceration but the mechanism of these complications has not been fully elucidated. The pathogenesis of stress-induced gastric damage involves the fall in Gastric Blood Flow (GBF), an increase in gastric acid secretion and gastric motility, enhanced adrenergic and cholinergic nerve activity and the rise in gastric mucosal generation of reactive oxygen species. The gastric mucosal defense mechanisms against the deleterious effect of stress include the activation of the hypothalamic-pituitary-adrenal axis which has been linked with glucocorticoids release capable of counteracting of stress-induced gastric lesions. Here we summarize the novel gastroprotective mechanisms against stress damage exhibited by angiotensin-(1-7), the newly discovered metabolite of Renin-Angiotensin System (RAS), the gaseous mediators such as nitric oxide (NO), hydrogen sulfide (H2S) or Carbon Monoxide (CO), and the food intake controlling peptides ghrelin, nesfatin- 1 and apelin possibly acting via brain-gut axis. These bioactive molecules such as RAS vasoactive metabolite angiotensin-(1-7) and appetite peptides have been shown to afford gastroprotective effect against stressinduced gastric lesions mainly mediated by an increase in gastric microcirculation. Gaseous mediators protect the gastric mucosa against stress lesions by mechanism involving the activation of PG/COX and CO/HO-1 biosynthetic pathways, and their anti-inflammatory and anti-oxidizing properties. Thus, these new components add new mechanistic aspects to the common cooperation of NO/NO-synthase, PG/COX systems and vasoactive sensory neuropeptides including CGRP but their gastroprotective efficacy against experimental stress ulcerogenesis requires the confirmation in human clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

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

    2016-10-01

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

  1. Reduced glomerular angiotensin II receptor density in diabetes mellitus in the rat: time course and mechanism

    International Nuclear Information System (INIS)

    Wilkes, B.M.

    1987-01-01

    Glomerular angiotensin II receptors are reduced in number in early diabetes mellitus, which may contribute to hyperfiltration and glomerular injury. The time course and role of the renin-angiotensin-aldosterone system in the pathogenesis of the receptor abnormality were studied in male Sprague-Dawley rats made diabetic with streptozotocin (65 mg, iv). Glomerular angiotensin II receptors were measured by Scatchard analysis; insulin, renin activity, angiotensin II, and aldosterone were measured by RIA. Diabetes mellitus was documented at 24 h by a rise in plasma glucose (vehicle-injected control, 133 +/- 4; diabetic, 482 +/- 22 mg/dl and a fall in plasma insulin (control, 53.1 +/- 5.7; diabetic, 35.6 +/- 4.0 microIU/ml. At 24 h glomerular angiotensin II receptor density was decreased by 26.5% in diabetic rats (control, 75.5 +/- 9.6 X 10(6); diabetic, 55.5 +/- 8.3 X 10(6) receptors/glomerulus. Receptor occupancy could not explain the defect, because there was reduced binding in diabetic glomeruli after pretreatment with 3 M MgCl 2 , a maneuver that caused dissociation of previously bound hormone. There was a progressive return of the receptor density toward normal over the 60 days following induction of diabetes, with diabetic glomeruli measuring 22.7%, 14.8%, and 3.7% fewer receptors than age-matched controls at 11 days, 1 month, and 2 months, respectively

  2. TO THE 110-TH ANNIVERSARY OF RENIN FINDING. FIGHT OF TITANS: ANGIOTENSIN CONVERTING ENZYME INHIBITORS AND SARTANS

    Directory of Open Access Journals (Sweden)

    L. N. Malay

    2009-01-01

    Full Text Available Angiotensin converting enzyme (ACE inhibitors and angiotensin II receptor blockers (ARB slow down progression of cardiovascular diseases and reduce risk of mortality and life threatening complications. What it is better to prescribe for patient in a concrete clinical case – ACE inhibitors or ARB? Authors compare these drug classes (mechanism of action, indications, evidense base of clinical trails, treatment costs and safety. The place of ACE inhibitors and ARB in modern therapy of cardiovascular diseases is defined. Results of the recent trails (ONTARGET, TRANCEND, PRoFESS, I-PRESERVE are discussed.

  3. Can Screening and Confirmatory Testing in the Management of Patients with Primary Aldosteronism be Improved?

    Science.gov (United States)

    Stowasser, Michael; Ahmed, Ashraf; Guo, Zeng; Wolley, Martin; Ungerer, Jacobus; McWhinney, Brett; Poglitsch, Marko; Gordon, Richard

    2017-12-01

    Widespread application of the plasma aldosterone/renin ratio (ARR) as a screening test has led to the recognition that primary aldosteronism (PA) is the most common specifically treatable and potentially curable form of hypertension, accounting for 5-10% of patients. Maximal detection requires accurate diagnostic approaches and awareness and control of factors that confound results, including most antihypertensives, posture, time of day, dietary salt, and plasma potassium. Recent studies have revealed potential for false positives in patients on beta-adrenoceptor blockers, and, when direct renin concentration (but not plasma renin activity) is used to measure renin, in women during the luteal phase of the menstrual cycle or receiving estrogen-containing contraceptives or hormonal replacement therapy. In addition to verapamil slow release, hydralazine and prazosin, moxonidine has minimal effects on the ARR and can be used to control hypertension during work-up. Fludrocortisone suppression testing, while probably the most reliable means of definitively confirming or excluding PA, is time consuming and expensive, requiring a five day inpatient stay. A novel approach, upright (seated) saline infusion suppression testing (SST), has shown excellent reliability with much greater sensitivity than conventional recumbent SST in a recent pilot study, and requires only a day visit. Accurate measurement of aldosterone is essential for each step of PA workup: introduction of new, highly reliable high-throughput mass spectrometric methods into clinical practice has represented a major advance. In response to concerns raised about accuracy of renin assays, new mass spectrometric methods for measuring angiotensin II are currently being assessed in the clinical setting. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Effects of renal denervation on cardiac oxidative stress and local activity of the sympathetic nervous system and renin-angiotensin system in acute myocardial infracted dogs.

    Science.gov (United States)

    Feng, Qiaoli; Lu, Chengzhi; Wang, Li; Song, Lijun; Li, Chao; Uppada, Ravi Chandra

    2017-02-17

    This study sought to evaluate the therapeutic effects of renal denervation (RDN) on acute myocardial infarction (MI) in canines and explore its possible mechanisms of action. Eighteen healthy mongrel dogs were randomly assigned to either the control group, the MI group or the MI + RDN group. To assess cardiac function, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and fraction shortening (FS) were recorded. Additionally, haemodynamic parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate (HR) were measured. Cardiac oxidative stress levels were evaluated based on the expression of p47 phox mRNA, malondialdehyde (MDA), anti-superoxide anion free radical (ASAFR) and activity of superoxide dismutase (SOD). To measure the local activity of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS), the levels of tyrosine hydroxylase (TH), angiotensin II (AngII), angiotensin-converting enzyme 2 (ACE2), angiotensin (1-7) [Ang(1-7)] and Mas receptor (MasR) in myocardial tissues were recorded. The expression of TH in renal tissue and serum creatinine were used to assess the effectiveness of the RDN procedure and renal function, respectively. We found that MI deteriorated heart function and activated cardiac oxidative stress and the local neurohumoral system, while RDN partially reversed these changes. Compared with the control group, parameters including LVEDD, LVESD, LVEDP and the levels of ASAFR, MDA, p47 phox ,ACE2, Ang(1-7), MasR, AngII and TH-positive nerves were increased (all P < 0.05) in myocardial infracted dogs; meanwhile, LVEF, FS, LVSP and SOD expression were decreased (all P < 0.05). However, after RDN therapy, these changes were significantly improved (P < 0.05), except that there were no significant differences observed in FS or LVSP between the two groups (P = 0

  5. High, but not low, exercise volume shifts the balance of renin-angiotensin system toward ACE2/Mas receptor axis in skeletal muscle in obese rats.

    Science.gov (United States)

    Frantz, Eliete Dalla Corte; Giori, Isabele Gomes; Machado, Marcus Vinícius; Magliano, D'Angelo Carlo; Freitas, Fernanda Marques; Andrade, Mariana Sodré Boêta; Vieira, Aline Bomfim; Nóbrega, Antonio Claudio Lucas; Tibiriçá, Eduardo

    2017-10-01

    Metabolic syndrome is a cluster of metabolic risk factors that is linked to central obesity, elevated blood pressure, insulin resistance (IR), and dyslipidemia, where the renin-angiotensin system (RAS) may provide a link among them. This study aimed to evaluate volume exercise effects comparing low vs. high volume of chronic aerobic exercise on RAS axes in skeletal muscle in a diet-induced obesity (DIO) rat model. For this, male Wistar-Kyoto rats were fed a standard chow (SC) diet or a high-fat (HF) diet for 32 wk. Animals receiving the HF diet were randomly divided into low exercise volume (LEV, 150 min/wk) and high exercise volume (HEV, 300 min/wk) at the 20th week. After 12 wk of aerobic treadmill training, the body mass and composition, blood pressure, glucose and lipid metabolism, RAS axes, insulin signaling, and inflammatory pathway were performed. HEV slowed the body mass gain, reduced intra-abdominal fat pad and leptin levels, improved total and peripheral body composition and inflammatory cytokine, reduced angiotensin II type 1 receptor expression, and increased Mas receptor protein expression compared with the HF animals. Sedentary groups (SC and HF) presented lower time to exhaustion and maximal velocity compared with the LEV and HEV groups. Both exercise training groups showed reduced resting systolic blood pressure and heart rate, improved glucose tolerance, IR, insulin signaling, and lipid profile. We conclude that the HEV, but not LEV, shifted the balance of RAS toward the ACE2/Mas receptor axis in skeletal muscle, presenting protective effects against the DIO model. Copyright © 2017 the American Physiological Society.

  6. Association between renin-angiotensin system antagonist use and mortality in heart failure with severe renal insufficiency: a prospective propensity score-matched cohort study.

    Science.gov (United States)

    Edner, Magnus; Benson, Lina; Dahlström, Ulf; Lund, Lars H

    2015-09-07

    In heart failure (HF) with reduced ejection fraction (EF), renin-angiotensin receptor (RAS) antagonists reduce mortality. However, severe renal insufficiency was an exclusion criterion in trials. We tested the hypothesis that RAS antagonists are associated with reduced mortality also in HF with severe renal insufficiency. We studied patients with EF ≤39% registered in the prospective Swedish Heart Failure Registry. In patients with creatinine >221 µmol/L or creatinine clearance renal insufficiency. Between 2000 and 2013, there were 24 283 patients of which 2410 [age, mean (SD), 82 (9), 45% women] had creatinine >221 µmol/L or creatinine clearance renal insufficiency [n = 21 873; age 71 (12), 27% women], the matched HR was 0.79 (95% CI 0.72-0.86, P renal insufficiency, the use of RAS antagonists was associated with lower all-cause mortality. Prospective randomized trials are needed before these findings can be applied to clinical practice. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  7. The Impact of Renin-Angiotensin System Blockade on Renal Outcomes and Mortality in Pre-Dialysis Patients with Advanced Chronic Kidney Disease.

    Science.gov (United States)

    Oh, Yun Jung; Kim, Sun Moon; Shin, Byung Chul; Kim, Hyun Lee; Chung, Jong Hoon; Kim, Ae Jin; Ro, Han; Chang, Jae Hyun; Lee, Hyun Hee; Chung, Wookyung; Lee, Chungsik; Jung, Ji Yong

    2017-01-01

    Renin-angiotensin-system (RAS) blockade is thought to slow renal progression in patients with chronic kidney disease (CKD). However, it remains uncertain if the habitual use of RAS inhibitors affects renal progression and outcomes in pre-dialysis patients with advanced CKD. In this multicenter retrospective cohort study, we identified 2,076 pre-dialysis patients with advanced CKD (stage 4 or 5) from a total of 33,722 CKD patients. RAS blockade users were paired with non-users for analyses using inverse probability of treatment-weighted (IPTW) and propensity score (PS) matching. The outcomes were renal death, all-cause mortality, hospitalization for hyperkalemia, and interactive factors as composite outcomes. RAS blockade users showed an increased risk of renal death in PS-matched analysis (hazard ratio [HR], 1.381; 95% CI, 1.071-1.781; P = 0.013), which was in agreement with the results of IPTW analysis (HR, 1.298; 95% CI, 1.123-1.500; P renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding RAS blockade may lead to better outcomes in these patients.

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

    Science.gov (United States)

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

    2010-11-01

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

  9. Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides.

    Science.gov (United States)

    Dave, Lakshmi A; Hayes, Maria; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

    2016-02-01

    It is well known that endogenous bioactive proteins and peptides play a substantial role in the body's first line of immunological defence, immune-regulation and normal body functioning. Further, the peptides derived from the luminal digestion of proteins are also important for body function. For example, within the peptide database BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/en/biopep) 12 endogenous antimicrobial and 64 angiotensin-I-converting enzyme (ACE-I) inhibitory peptides derived from human milk and plasma proteins are listed. The antimicrobial peptide database (http://aps.unmc.edu/AP/main.php) lists over 111 human host-defence peptides. Several endogenous proteins are secreted in the gut and are subject to the same gastrointestinal digestion processes as food proteins derived from the diet. The human gut endogenous proteins (GEP) include mucins, serum albumin, digestive enzymes, hormones, and proteins from sloughed off epithelial cells and gut microbiota, and numerous other secreted proteins. To date, much work has been carried out regarding the health altering effects of food-derived bioactive peptides but little attention has been paid to the possibility that GEP may also be a source of bioactive peptides. In this review, we discuss the potential of GEP to constitute a gut cryptome from which bioactive peptides such as ACE-I inhibitory, renin inhibitory and antioxidant peptides may be derived. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Shasanka S Panda

    2013-01-01

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

  12. Combined use of drugs inhibiting the renin-angiotensin system: prescribing patterns and risk of acute kidney injury in German nursing home residents.

    Science.gov (United States)

    Dörks, Michael; Herget-Rosenthal, Stefan; Hoffmann, Falk; Jobski, Kathrin

    2018-01-01

    In 2012, the European Medicines Agency reviewed the safety of dual renin-angiotensin system (RAS) blockade because of potentially increased risks for inter alia acute kidney injury (AKI). Since residents of nursing homes are particularly vulnerable to adverse drug outcomes, the aims of our study were to describe RAS-inhibiting drug use in German nursing home residents and examine the risk of AKI associated with dual RAS blockade. Based on claims data, a nested case-control study within a cohort of RAS-inhibiting drug users was conducted. Using conditional logistic regression, confounder-adjusted odds ratios (aORs) and 95% confidence intervals (CI) were obtained for the risk of AKI associated with dual RAS blockade. Subgroup analyses were performed in patients with diabetes or chronic kidney disease and both comorbidities. Of all 127,227 nursing home residents, the study cohort included 64,567 (50.7%) who were treated with at least one RAS-inhibiting drug. More than three quarters of the study population were female (77.1%). Mean age was 86.0 ± 6.8 years. Most residents were treated with angiotensin-converting enzyme inhibitors (77.8%), followed by angiotensin II receptor blockers (21.6%) and aliskiren (0.2%). Annual prevalence of dual RAS blockade declined from 9.6 (95% CI 7.8-11.8) in 2010 to 4.7 (95% CI 4.0-5.4) per 1,000 users in 2014. In the overall cohort, AKI was not significantly associated with dual RAS blockade (aOR 1.99; 0.77-5.17). However, significantly increased aORs were observed when considering patients with diabetes (3.47; 1.27-9.47), chronic kidney disease (4.74; 1.24-18.13) or both (11.17; 2.65-47.15). Prescribing of drugs inhibiting the RAS is common in German nursing homes. Though the prevalence of dual RAS blockade declined, our study showed an increased risk of AKI in patients with diabetes and/or chronic kidney disease. Therefore, cautious use is warranted in these vulnerable patients.

  13. Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses.

    Science.gov (United States)

    Catalá-López, Ferrán; Macías Saint-Gerons, Diego; González-Bermejo, Diana; Rosano, Giuseppe M; Davis, Barry R; Ridao, Manuel; Zaragoza, Abel; Montero-Corominas, Dolores; Tobías, Aurelio; de la Fuente-Honrubia, César; Tabarés-Seisdedos, Rafael; Hutton, Brian

    2016-03-01

    Medications aimed at inhibiting the renin-angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes. Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014). Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke-singly and as a composite endpoint, major cardiovascular outcome-and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality-singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants), with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90-1.18), ACE inhibitor plus ARB (0.97; 95% CrI 0.79-1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96-1.81), and DR inhibitor plus ARB (1.00; 95% CrI 0.73-1.38). For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90-1.40), ACE inhibitor plus ARB (0.97; 95% CrI 0.72-1.29), DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65-1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78-1.84). No significant differences were showed between ACE inhibitors and ARBs with

  14. Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses.

    Directory of Open Access Journals (Sweden)

    Ferrán Catalá-López

    2016-03-01

    Full Text Available Medications aimed at inhibiting the renin-angiotensin system (RAS have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes.Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014. Interventions of interest were angiotensin-converting enzyme (ACE inhibitors, angiotensin receptor blockers (ARBs, and direct renin (DR inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke-singly and as a composite endpoint, major cardiovascular outcome-and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality-singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants, with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90-1.18, ACE inhibitor plus ARB (0.97; 95% CrI 0.79-1.19, DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96-1.81, and DR inhibitor plus ARB (1.00; 95% CrI 0.73-1.38. For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90-1.40, ACE inhibitor plus ARB (0.97; 95% CrI 0.72-1.29, DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65-1.57, and DR inhibitor plus ARB (1.18; 95% CrI 0.78-1.84. No significant differences were showed between ACE inhibitors and ARBs with

  15. Reduced plasma aldosterone concentrations in randomly selected patients with insulin-dependent diabetes mellitus.

    LENUS (Irish Health Repository)

    Cronin, C C

    2012-02-03

    Abnormalities of the renin-angiotensin system have been reported in patients with diabetes mellitus and with diabetic complications. In this study, plasma concentrations of prorenin, renin, and aldosterone were measured in a stratified random sample of 110 insulin-dependent (Type 1) diabetic patients attending our outpatient clinic. Fifty-four age- and sex-matched control subjects were also examined. Plasma prorenin concentration was higher in patients without complications than in control subjects when upright (geometric mean (95% confidence intervals (CI): 75.9 (55.0-105.6) vs 45.1 (31.6-64.3) mU I-1, p < 0.05). There was no difference in plasma prorenin concentration between patients without and with microalbuminuria and between patients without and with background retinopathy. Plasma renin concentration, both when supine and upright, was similar in control subjects, in patients without complications, and in patients with varying degrees of diabetic microangiopathy. Plasma aldosterone was suppressed in patients without complications in comparison to control subjects (74 (58-95) vs 167 (140-199) ng I-1, p < 0.001) and was also suppressed in patients with microvascular disease. Plasma potassium was significantly higher in patients than in control subjects (mean +\\/- standard deviation: 4.10 +\\/- 0.36 vs 3.89 +\\/- 0.26 mmol I-1; p < 0.001) and plasma sodium was significantly lower (138 +\\/- 4 vs 140 +\\/- 2 mmol I-1; p < 0.001). We conclude that plasma prorenin is not a useful early marker for diabetic microvascular disease. Despite apparently normal plasma renin concentrations, plasma aldosterone is suppressed in insulin-dependent diabetic patients.

  16. Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition

    Science.gov (United States)

    Hubers, Scott A.; Brown, Nancy J.

    2016-01-01

    Heart failure affects approximately 5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the FDA 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 two of the pathophysiologic 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 to 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 pharmacologic properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension. PMID:26976916

  17. Angiotensin II Receptor Blockers

    Science.gov (United States)

    ... 2010. Mann JFE, et al. Renin-angiotensin system inhibition in the treatment of hypertension. http://www.uptodate. ... profit organization and proceeds from Web advertising help support our mission. Mayo Clinic does not endorse any ...

  18. Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease.

    Science.gov (United States)

    Ishigaki, Sayaka; Ohashi, Naro; Isobe, Shinsuke; Tsuji, Naoko; Iwakura, Takamasa; Ono, Masafumi; Sakao, Yukitoshi; Tsuji, Takayuki; Kato, Akihiko; Miyajima, Hiroaki; Yasuda, Hideo

    2016-12-01

    Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. The circadian rhythm of intrarenal RAS activation leads to renal damage and hypertension, which are associated with diurnal blood pressure (BP) variation. The activation of intrarenal RAS following reactive oxygen species (ROS) activation, sympathetic hyperactivity and nitric oxide (NO) inhibition leads to the development of renal damage. Melatonin is a hormone regulating the circadian rhythm, and has multiple functions such as anti-oxidant and anti-adrenergic effects and enhancement of NO bioavailability. Nocturnal melatonin concentrations are lower in CKD patients. However, it is not known if impaired endogenous melatonin secretion is related to BP, intrarenal RAS, or renal damage in CKD patients. We recruited 53 CKD patients and conducted 24-h ambulatory BP monitoring. urine was collected during the daytime and nighttime. We investigated the relationship among the melatonin metabolite urinary 6-sulphatoxymelatonin (U-aMT6s), BP, renal function, urinary angiotensinogen (U-AGT), and urinary albumin (U-Alb). Patients' U-aMT6s levels were significantly and negatively correlated with clinical parameters such as renal function, systolic BP, U-AGT, and U-Alb, during both day and night. Multiple regression analyses for U-aMT6s levels were performed using age, gender, renal function, and each parameter (BPs, U-AGT or U-Alb), at daytime and nighttime. U-aMT6s levels were significantly associated with U-AGT (β = -0.31, p = 0.044) and U-Alb (β = -0.25, p = 0.025) only at night. Impaired nighttime melatonin secretion may be associated with nighttime intrarenal RAS activation and renal damage in CKD patients.

  19. Effect of Sodium-Glucose Co-Transporter 2 Inhibitor, Dapagliflozin, on Renal Renin-Angiotensin System in an Animal Model of Type 2 Diabetes.

    Science.gov (United States)

    Shin, Seok Joon; Chung, Sungjin; Kim, Soo Jung; Lee, Eun-Mi; Yoo, Young-Hye; Kim, Ji-Won; Ahn, Yu-Bae; Kim, Eun-Sook; Moon, Sung-Dae; Kim, Myung-Jun; Ko, Seung-Hyun

    2016-01-01

    Renal renin-angiotensin system (RAS) activation is one of the important pathogenic mechanisms in the development of diabetic nephropathy in type 2 diabetes. The aim of this study was to investigate the effects of a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, dapagliflozin, on renal RAS in an animal model with type 2 diabetes. Dapagliflozin (1.0 mg/kg, OL-DA) or voglibose (0.6 mg/kg, OL-VO, diabetic control) (n = 10 each) was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats for 12 weeks. We used voglibose, an alpha-glucosidase inhibitor, as a comparable counterpart to SGLT2 inhibitor because of its postprandial glucose-lowering effect without proven renoprotective effects. Control Long-Evans Tokushima Otsuka (LT) and OLETF (OL-C) rats received saline (n = 10, each). Changes in blood glucose, urine albumin, creatinine clearance, and oxidative stress were measured. Inflammatory cell infiltration, mesangial widening, and interstitial fibrosis in the kidney were evaluated by histological analysis. The effects of dapagliflozin on renal expression of the RAS components were evaluated by quantitative RT-PCR in renal tissue. After treatment, hyperglycemia and urine microalbumin levels were attenuated in both OL-DA and OL-VO rather than in the OL-C group (P renal RAS component expression, oxidative stress and interstitial fibrosis in OLETF rats. We suggest that, in addition to control of hyperglycemia, partial suppression of renal RAS with an SGLT2 inhibitor would be a promising strategy for the prevention of treatment of diabetic nephropathy.

  20. Renin-Angiotensin System Inhibitors, Type 2 Diabetes and Fibrosis Progression: An Observational Study in Patients with Nonalcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Serena Pelusi

    Full Text Available The clinical determinants of fibrosis progression in nonalcoholic fatty liver disease (NAFLD are still under definition.To assess the clinical determinants of fibrosis progression rate (FPR in NAFLD patients with baseline and follow-up histological evaluation, with a special focus on the impact of pharmacological therapy.In an observational cohort of 118 Italian patients from tertiary referral centers, liver histology was evaluated according to Kleiner. Independent predictors of FPR were selected by a stepwise regression approach.Median follow-up was 36 months (IQR 24-77. Twenty-five patients (18% showed some amelioration, 63 (53% had stability, 30 (25% had progression of fibrosis. Patients with nonalcoholic steatohepatitis (NASH had similar demographic and anthropometric features, but a higher prevalence of type 2 diabetes (T2D; p = 0.010, and use of renin-angiotensin axis system (RAS inhibitors (p = 0.005. Fibrosis progression was dependent of the length of follow-up, and was associated with, but did not require, the presence of NASH (p<0.05. Both fibrosis progression and faster FPR were independently associated with higher APRI score at follow-up, absence of treatment with RAS inhibitors, and T2D diagnosis at baseline (p<0.05. There was a significant interaction between use of RAS inhibitors and T2D on FPR (p = 0.002. RAS inhibitors were associated with slower FPR in patients with (p = 0.011, but not in those without (p = NS T2D.NASH is not required for fibrosis progression in NAFLD, whereas T2D seems to drive fibrogenesis independently of hepatic inflammation. Use of RAS inhibitors may contrast fibrosis progression especially in high-risk patients affected by T2D.

  1. Exposure to fine particulate matter in the air alters placental structure and the renin-angiotensin system.

    Directory of Open Access Journals (Sweden)

    Sônia de Fátima Soto

    Full Text Available Female Wistar rats were exposed to filtered air (F or to concentrated fine particulate matter (P for 15 days. After mating, the rats were divided into four groups and again exposed to F or P (FF, FP, PF, PP beginning on day 6 of pregnancy. At embryonic day 19, the placenta was collected. The placental structure, the protein and gene expression of TGFβ1, VEGF-A, and its receptor Flk-1 and RAS were evaluated by indirect ELISA and quantitative real-time PCR.Exposure to P decreased the placental mass, size, and surface area as well as the TGFβ1, VEGF-A and Flk-1 content. In the maternal portion of the placenta, angiotensin II (AngII and its receptors AT1 (AT1R and AT2 (AT2R were decreased in the PF and PP groups. In the fetal portion of the placenta, AngII in the FP, PF and PP groups and AT2R in the PF and PP groups were decreased, but AT1R was increased in the FP group. VEGF-A gene expression was lower in the PP group than in the FF group.Exposure to pollutants before and/or during pregnancy alters some characteristics of the placenta, indicating a possible impairment of trophoblast invasion and placental angiogenesis with possible consequences for the maternal-fetal interaction, such as a limitation of fetal nutrition and growth.

  2. Differential control of collagen synthesis by the sympathetic and renin-angiotensin systems in the rat left ventricle.

    Science.gov (United States)

    Dab, Houcine; Hachani, Rafik; Hodroj, Wassim; Sakly, Mohsen; Bricca, Giampiero; Kacem, Kamel

    2009-12-03

    In the present study, we tested the hypothesis of the indirect (via the sympathetic nervous system (SNS)) and direct (via AT1 receptors) contributions of Angiotensin II (Ang II) on the synthesis of collagen types I and III in the left ventricle (LV) in vivo. Sympathectomy and blockade of the Ang II receptor AT1 were performed alone or in combination in normotensive rats. The mRNA and protein synthesis of collagen types I and III were examined by Q-RT-PCR and immunoblotting in the LV. Collagen types I and III mRNA were decreased respectively by 53% and 22% after sympathectomy and only collagen type I mRNA was increased by 52% after AT1 receptor blockade. mRNA was not changed for collagen type I but was decreased by 25% for collagen type III after double treatment. Only collagen protein type III was decreased after sympathectomy by 12%, but collagen proteins were increased respectively for types I and III by 145% and 52% after AT1 receptor blockade and by 45% and 60% after double treatment. Deducted interpretations from our experimental approach suggest that Ang II stimulates indirectly (via SNS) and inhibits directly (via AT1 receptors) the collagen type I at transcriptional and protein levels. For collagen type III, it stimulates indirectly the transcription and inhibited directly the protein level. Therefore, the Ang II regulates collagen synthesis differently through indirect and direct pathways.

  3. Clinical significance of determination of SAC/PRA value in patients with primary aldosteronism

    International Nuclear Information System (INIS)

    Li Liren; Dai Yaozong; Liu Jiumin

    2003-01-01

    Objective: To investigate the diagnostic significance of determining SAC/PRA valve in hyperaldosteronism. Methods: Plasma renin activity (PRA) and angiotensin (AT-II) as well as serum aldosterone contents were measured with RIA in 48 patients with primary aldosteronism and 30 controls. The SAC/PRA value was calculated. Results: Contents of PRA, AT-II and Aldo in blood of patients with primary aldosteronism were very significantly different from those in controls (p < 0.001) (PRA 0.14 ± 0.08 ng/ml/h vs 0.57 ± 0.08 ng/ml/h; AT-II 21.21 ± 7.55 ng/L vs 36.03 ± 6.11 ng/L; Aldo 1.07 ± 0.34 nmol/L vs 0.33 ± 0.04 nmol/L). Calculated SAC/PRA value was 913 ± 409 (normal upper limit 400). Conclusion: SAC/PRA value is an useful accessory diagnostic criterion for primary aldosteronism

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

    Science.gov (United States)

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

    2017-11-15

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

  5. 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.

  6. Analysis of postoperative biochemical values and clinical outcomes after adrenalectomy for primary aldosteronism.

    Science.gov (United States)

    Swearingen, Andrew J; Kahramangil, Bora; Monteiro, Rosebel; Krishnamurthy, Vikram; Jin, Judy; Shin, Joyce; Siperstein, Allan; Berber, Eren

    2018-04-01

    Primary aldosteronism causes hypertension and hypokalemia and is often surgically treatable. Diagnosis includes elevated plasma aldosterone, suppressed plasma renin activity, and elevated aldosterone renin ratio. Adrenalectomy improves hypertension and hypokalemia. Postoperative plasma aldosterone and plasma renin activity may be useful in documenting cure or failure. A retrospective analysis of patients who underwent adrenalectomy for primary aldosteronism from 2010 to 2016 was performed, analyzing preoperative and postoperative plasma aldosterone, plasma renin activity, hypertension, and hypokalemia. The utility of postoperative testing was assessed. Clinical cure was defined as improved hypertension control and resolution of potassium loss. Biochemical cure was defined as aldosterone renin ratio reduction to <23.6. Forty-four patients were included; 20 had plasma aldosterone and plasma renin activity checked on postoperative day 1. In the study, 40/44 (91%) were clinically cured. All clinical failures had of biochemical failure at follow-up. Postoperative day 1aldosterone renin ratio <23.6 had PPV of 95% for clinical cure. Cured patients had mean plasma aldosterone drop of 33.1 ng/dL on postoperative day 1; noncured patient experienced 3.9 ng/dL increase. A cutoff of plasma aldosterone decrease of 10 ng/dL had high positive predictive value for clinical cure. Changes in plasma aldosterone and plasma renin activity after adrenalectomy correlate with improved hypertension and hypokalemia. The biochemical impact of adrenalectomy manifests as early as postoperative day 1. We propose a plasma aldosterone decrease of 10 ng/dL as a criterion to predict clinical cure. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Aldosterone breakthrough in dogs with naturally occurring myxomatous mitral valve disease.

    Science.gov (United States)

    Ames, M K; Atkins, C E; Eriksson, A; Hess, A M

    2017-06-01

    Aldosterone breakthrough (ABT) is the condition in which angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers fail to effectively suppress the activity of the renin angiotensin aldosterone system. The objective of this study was to determine if ABT occurs in dogs with naturally occurring myxomatous mitral valve disease receiving an ACEI, using the urine aldosterone to creatinine ratio (UAldo:C) as a measure of renin angiotensin aldosterone system activation. This study includes 39 dogs with myxomatous mitral valve disease. A UAldo:C cut-off definition (derived from a normal population of healthy, adult, and client-owned dogs) was used to determine the prevalence of ABT in this population. Spearman analysis and univariate logistic regression were used to evaluate the relationship between UAldo:C and ABT (yes/no) and eight variables (age, serum K + concentration, serum creatinine concentration, ACEI therapy duration and ACEI dosage, furosemide therapy duration and furosemide dosage, and urine sample storage time). Finally, the UAldo:C in dogs receiving spironolactone, as part congestive heart failure (CHF) therapy, was compared to dogs with CHF that were not receiving spironolactone. The prevalence of ABT was 32% in dogs with CHF and 30% in dogs without CHF. There was no relationship between either the UAldo:C or the likelihood of ABT and the eight variables. Therapy with spironolactone lead to a significant elevation of the UAldo:C. Using the UAldo:C and a relatively stringent definition of ABT, it appears that incomplete RAAS blockade is common in dogs with MMVD receiving an ACEI. The prevalence of ABT in this canine population mirrors that reported in humans. While the mechanism of ABT is likely multifactorial and still poorly understood, the proven existence of ABT in dogs offers the potential to improve the prognosis for MMVD with the addition of a mineralocorticoid receptor blocker to current therapeutic regimens

  8. Renal renin secretion as regulator of body fluid homeostasis

    DEFF Research Database (Denmark)

    Damkjær, Mads; Isaksson, Gustaf L; Stubbe, Jane

    2013-01-01

    The renin-angiotensin system is essential for body fluid homeostasis and blood pressure regulation. This review focuses on the homeostatic regulation of the secretion of active renin in the kidney, primarily in humans. Under physiological conditions, renin secretion is determined mainly by sodium...

  9. Pitting type of pretibial edema in a patient with silent thyroiditis successfully treated by angiotensin ii receptor blockade.

    Science.gov (United States)

    Kazama, Itsuro; Mori, Yoko; Baba, Asuka; Nakajima, Toshiyuki

    2014-01-01

    Female, 56 FINAL DIAGNOSIS: Thyroiditis - silent Symptoms: Palpitations • pretibial pitting edema • short of breath • sweating - Clinical Procedure: - Specialty: Endocrinology and Metabolic. Unknown etiology. Hyper- or hypothyroidism sometimes causes pretibial myxedema characterized by non-pitting infiltration of a proteinaceous ground substance. However, in those patients, the "pitting" type of pretibial edema as a result of increased sodium and fluid retention or vascular hyper-permeability rarely occurs, except in cases complicated by heart failures due to severe cardiomyopathy or pulmonary hypertension. A 56-year-old woman developed bilateral pretibial pitting edema, followed by occasional sweating, palpitations, and shortness of breath, which persisted for more than 2 months. The diagnosis of hyperthyroidism due to silent thyroiditis was supported by elevated levels of free thyroxine (T4) and triiodothyronine (T3), with a marked decrease in thyroid-stimulating hormone (TSH), and the negative results for TSH receptor antibodies with typical findings of destructive thyrotoxicosis. Despite her "pitting" type of pretibial edema, a chest radio-graph demonstrated the absence of cardiomyopathy or congestive heart failure. Oral administration of angiotensin II receptor blocker (ARB) was initiated for her systolic hypertension, with a relatively higher elevation of plasma renin activity compared to that of the aldosterone level. Although the symptoms characteristic to hyperthyroidism, such as increased sweating, palpitations and shortness of breath, slowly improved with a spontaneous resolution of the disease, ARB quickly resolved the pretibial pitting edema shortly after the administration.. In this case, increased activity of the renin-angiotensin-aldosterone system stimulated by thyroid hormone was likely responsible for the patient's pitting type of edema. The pharmacological blockade of the renin-angiotensin-aldosterone system was thought to be effective for

  10. Low birth weight in response to salt restriction during pregnancy is not due to alterations in uterine-placental blood flow or the placental and peripheral renin-angiotensin system.

    Science.gov (United States)

    Leandro, Sandra Márcia; Furukawa, Luzia Naôko Shinohara; Shimizu, Maria Heloisa Massola; Casarini, Dulce Elena; Seguro, Antonio Carlos; Patriarca, Giuliana; Coelho, Michella Soares; Dolnikoff, Miriam Sterman; Heimann, Joel Claudio

    2008-09-03

    A number of studies conducted in humans and in animals have observed that events occurring early in life are associated with the development of diseases in adulthood. Salt overload and restriction during pregnancy and lactation are responsible for functional (hemodynamic and hormonal) and structural alterations in adult offspring. Our group observed that lower birth weight and insulin resistance in adulthood is associated with salt restriction during pregnancy. On the other hand, perinatal salt overload is associated with higher blood pressure and higher renal angiotensin II content in adult offspring. Therefore, we hypothesised that renin-angiotensin system (RAS) function is altered by changes in sodium intake during pregnancy. Such changes may influence fetoplacental blood flow and thereby fetal nutrient supply, with effects on growth in utero and, consequently, on birth weight. Female Wistar rats were fed low-salt (LS), normal-salt (NS), or high-salt (HS) diet, starting before conception and continuing until day 19 of pregnancy. Blood pressure, heart rate, fetuses and dams' body weight, placentae weight and litter size were measured on day 19 of pregnancy. Cardiac output, uterine and placental blood flow were also determined on day 19. Expressions of renin-angiotensin system components and of the TNF-alpha gene were evaluated in the placentae. Plasma renin activity (PRA) and plasma and tissue angiotensin-converting enzyme (ACE) activity, as well as plasma and placental levels of angiotensins I, II, and 1-7 were measured. Body weight and kidney mass were greater in HS than in NS and LS dams. Food intake did not differ among the maternal groups. Placental weight was lower in LS dams than in NS and HS dams. Fetal weight was lower in the LS group than in the NS and HS groups. The PRA was greater in LS dams than in NS and HS dams, although ACE activity (serum, cardiac, renal, and placental) was unaffected by the level of sodium intake. Placental levels of

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

    Directory of Open Access Journals (Sweden)

    Ke Li

    2017-01-01

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

  12. 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. 

  13. Direct renin inhibition — a new way of targeting the renin system

    Directory of Open Access Journals (Sweden)

    Morris J Brown

    2006-06-01

    Full Text Available The renin system plays a key role in the pathology of hypertension and is influenced, both directly and indirectly, by most antihypertensive agents. The system is the target of several established classes of antihypertensive agents including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers. Of currently available drugs, only the beta-blockers suppress renin secretion, but these also reduce heart rate and cardiac output. Calcium channel blockers and diuretics cause a modest activation of the renin system secondary to the fall in renal afferent arteriolar pressure and reduction in filtered sodium load. Aliskiren is the first orally available direct inhibitor that blocks the renin system at its rate limiting step and is shown to reduce angiotensin I and II and plasma renin activity.

  14. The renin-angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis

    OpenAIRE

    Arganaraz, Gustavo Adolfo [UNIFESP; Konno, Ana Carla [UNIFESP; Perosa, Sandra Regina [UNIFESP; Santiago, Joselita Ferreira Carvalho [UNIFESP; Boim, Mirian A. [UNIFESP; Vidotti, Daniela Berguio [UNIFESP; Varella, Pedro Paulo Vasconcellos [UNIFESP; Costa, Luciana Gilbert [UNIFESP; Canzian, Mauro; Porcionatto, Marimelia Aparecida [UNIFESP; Yacubian, Elza Marcia [UNIFESP; Sakamoto, Americo Ceiki [UNIFESP; Carrete, Henrique [UNIFESP; Centeno, Ricardo Silva [UNIFESP; Amado, Debora [UNIFESP

    2008-01-01

    Purpose: As reported by several authors, angiotensin II (AngII) is a proinflammatory molecule that stimulates the release of inflammatory cytokines and activates nuclear factor kappa B (NF kappa B), being also associated with the increase of cellular oxidative stress. Its production depends on the activity of the angiotensin converting enzyme (ACE) that hydrolyzes the inactive precursor angiotensin I (AngI) into AngII. It has been suggested that AngII underlies the physiopathological mechanis...

  15. Role of the inhibitors of angiotensin renin system on the DNA integrity of irradiated spermatozoids; Papel dos inibidores dos sistema renina angiotensina sobre a integridade do DNA de espermatozoides irradiados

    Energy Technology Data Exchange (ETDEWEB)

    Spadella, Maria A.; Mansano, Naira S.; Schwarz, Franciele C.; Viani, Gustavo A.; Chies, Agnaldo B. [Faculdade de Medicina de Marilia (FAMEMA), Marilia, SP (Brazil)

    2016-07-01

    Radiation action in the testes can significantly affect the reproductive capacity due to oxidative stress generated; phenomenon in which there is evidence of involvement of the Renin Angiotensin System (RAS). This study evaluated the role of AT1 receptor inhibitors, in mitigating the radioinduced DNA damage sperm from semen samples left vas deferens. Male Wistar rats were divided into six experimental groups: Control, 5Gy, Telmisartan (12mg/kg/day) and Losartan (34mg/kg/2x/day), 5 Gy + Telmisartan and 5 Gy + Losartan. The results showed increase in the percentage of sperm with fragmented DNA in irradiated groups when compared to controls, which was not reversed in the irradiated and treated groups. The radiation of 5Gy (single dose) affected the DNA-protein complex of the sperm and the treatments did not influence in reversing this damage, considering the experimental protocol used. (author)

  16. Differential clinical profile of candesartan compared to other angiotensin receptor blockers

    Directory of Open Access Journals (Sweden)

    Zimlichman R

    2011-12-01

    Full Text Available Relu Cernes1,2, Margarita Mashavi1,3, Reuven Zimlichman1,31The Brunner Institute for Cardiovascular Research, Wolfson Medical Center and Tel Aviv University, Tel Aviv, Israel; 2Department of Nephrology, Wolfson Medical Center, Holon, Israel; 3Department of Medicine, Wolfson Medical Center, Holon, IsraelAbstract: The advantages of blood pressure (BP control on the risks of heart failure and stroke are well established. The renin-angiotensin system plays an important role in volume homeostasis and BP regulation and is a target for several groups of antihypertensive drugs. Angiotensin II receptor blockers represent a major class of antihypertensive compounds. Candesartan cilexetil is an angiotensin II type 1 (AT[1] receptor antagonist (angiotensin receptor blocker [ARB] that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system. Oral candesartan 8–32 mg once daily is recommended for the treatment of adult patients with hypertension. Clinical trials have demonstrated that candesartan cilexetil is an effective agent in reducing the risk of cardiovascular mortality, stroke, heart failure, arterial stiffness, renal failure, retinopathy, and migraine in different populations of adult patients including patients with coexisting type 2 diabetes, metabolic syndrome, or kidney impairment. Clinical evidence confirmed that candesartan cilexetil provides better antihypertensive efficacy than losartan and is at least as effective as telmisartan and valsartan. Candesartan cilexetil, one of the current market leaders in BP treatment, is a highly selective compound with high potency, a long duration of action, and a tolerability profile similar to placebo. The most important and recent data from clinical trials regarding candesartan cilexetil will be reviewed in this article.Keywords: angiotensin receptor blockers, candesartan, candesartan cilexetil, clinical trials, efficacy studies, safety, blood pressure

  17. Radioimmunoassay of renin in human renal tissues

    International Nuclear Information System (INIS)

    Wowra, B.

    1981-01-01

    A method has been developed to quantitatively determine renin in human kidney tissue. The angiotensin I split off angiotensinogs by renin was radioimmunologically determined. The renin-renin substrate reaction rate followed a saturation kinetics, as it increased the larger the substrate content in the incubation medium until it acquired a maximum value; the reaction rate decreased with substrate concentrations over 40 mg/ml incubation medium. The discontinuance of the renin reaction after incubation by adding acid, boiling and neutralizing again, gave highest renin values. The RIA scattering was 8.3% for double determination of the same sample, for the determination in different RIA additions 7.0%. The detection limit was 20 pg angiotensin I. A direct comparison of radioimmunoassay and bioassay exhibited a very significant agreement of both methods, where the radioimmunologically measured renin values were on average four times larger than those obtained using biological technique. The definition of the so-called normal values for absolute and specific renin concentration in human kidney tissue enabled one to assess the renin values in various syndromes. (orig./MG) [de

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

    DEFF Research Database (Denmark)

    Peters, Christian Daugaard; 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......, and residual renal function. Brachial blood pressure decreased significantly in both groups, but there was no significant difference between placebo and irbesartan. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different. Intermediate cardiovascular end...... points such as central aortic blood pressure, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal brain natriuretic prohormone, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic blood pressure during...

  19. Relationship between angiotensin-converting enzyme gene polymorphism and cardio-brain complications in patients with NIDDM (type 2 diabetes mellitus)

    International Nuclear Information System (INIS)

    Xu Qinfang; Zhu Yan; Ding Mingwei

    2002-01-01

    Objective: To investigate the relationship between angiotensin-converting enzyme gene polymorphism and cardio-brain complications in patients with NIDDM. Methods: The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism in 174 patients with NIDDM and 62 controls were examined with PCR. Results: ACE gene I/D polymorphism was closely related to coronary heart disease (angina, cardiac infarction) and cerebral infarction in diabetic patients but not with hypertension. Plasma renin activity and plasma angiotensin II levels in complicated diabetic patients with ACE D/D gene were significantly higher than those in the controls (p < 0.01). Their aldosterone and endothelin contents were not significantly different. Conclusion: Examination of ACE gene I/D polymorphism was useful for the primary prevention of cardio-brain complications in diabetic patients and helpful in the early diagnosis and therapy of coronary heart disease and cerebral infarction

  20. Stress-induced Aldosterone Hyper-Secretion in a Substantial Subset of Patients With Essential Hypertension.

    Science.gov (United States)

    Markou, Athina; Sertedaki, Amalia; Kaltsas, Gregory; Androulakis, Ioannis I; Marakaki, Chrisanthi; Pappa, Theodora; Gouli, Aggeliki; Papanastasiou, Labrini; Fountoulakis, Stelios; Zacharoulis, Achilles; Karavidas, Apostolos; Ragkou, Despoina; Charmandari, Evangelia; Chrousos, George P; Piaditis, George P

    2015-08-01

    Aldosterone (ALD) secretion is regulated mainly by angiotensin II, K(+), and adrenocorticotropic hormone (ACTH). Mineralocorticoid receptor antagonists (MRAs) have effectively been used for the treatment of patients with hypertension who do not have primary aldosteronism (PA). We tested whether chronic stress-related ACTH-mediated ALD hypersecretion and/or zona glomerulosa hypersensitivity could be implicated in the pathogenesis of essential hypertension (ESHT). One hundred thirteen hypertensives without PA and 61 normotensive controls underwent an ultralow-dose (0.03-μg) ACTH stimulation and a treadmill test. Patients with ALD hyper-response according to the cutoffs obtained from controls received treatment with MRAs and underwent genomic DNA testing for the presence of the CYP11B1/CYP11B2 chimeric gene and KCNJ5 gene mutations. A control group of 22 patients with simple ESHT received treatment with MRAs. Based on the cutoffs of ALD and aldosterone-to-renin ratio (ARR) post-ACTH stimulation obtained from controls, 30 patients (27%) exhibited an ALD but not cortisol (F) hyper-response (HYPER group). This group had no difference in basal ACTH/renin (REN) concentrations compared with controls and the 83 patients with hypertension (73%) without an ALD hyper-response to ACTH stimulation. Patients in the HYPER group demonstrated significantly higher ALD concentrations, ARR, and ALD/ACTH ratio (AAR) in the treadmill test. Treatment with MRAs alone produced normalization of blood pressure in these patients whereas patients with hypertension with neither PA nor ALD hyper-response to ACTH stimulation who served as a control group failed to lower blood pressure. Also, two novel germline heterozygous KCNJ5 mutations were detected in the HYPER group. A number of patients with hypertension without PA show ACTH-dependent ALD hyper-secretion and benefit from treatment with MRAs. This could be related to chronic stress via ACTH hyper secretion and/or gene-mutations increasing the

  1. Aldosterone blood test

    Science.gov (United States)

    ... Addison disease - serum aldosterone; Primary hyperaldosteronism - serum aldosterone; Bartter syndrome - serum aldosterone ... normal level of aldosterone may be due to Bartter syndrome (group of rare conditions that affect the kidneys) ...

  2. Angiotensin II and Renal Tubular Ion Transport

    Directory of Open Access Journals (Sweden)

    Patricia Valles

    2005-01-01

    Evidence for the regulation of H+-ATPase activity in vivo and in vitro by trafficking/exocytosis has been provided. An additional level of H+-ATPase regulation via protein synthesis may be important as well. Recently, we have shown that both aldosterone and angiotensin II provide such a mechanism of regulation in vivo at the level of the medullary collecting tubule. Interestingly, in this part of the nephron, the effects of aldosterone and angiotensin II are not sodium dependent, whereas in the cortical collecting duct, both aldosterone and angiotensin II, by contrast, affect H+ secretion by sodium-dependent mechanisms.

  3. A Late Diagnosis of Primary Aldosteronism.

    Science.gov (United States)

    Zorzi, Francesco; Olivieri, Oliviero; Brazzarola, Paolo; Pizzolo, Francesca

    2017-09-01

    We report the case of a 41-year-old male patient with juvenile onset refractory hypertension while taking four drugs including a diuretic. Fourteen years before he underwent a complete investigation for secondary hypertension (including the aldosterone to renin ratio-ARR) that was negative. Since that, hypertension control gradually worsened, hypertensive organ damage aggravated and hypokalemia developed in spite of ACE inhibitor treatment. At the re-evaluation ARR was elevated, and the further workup for primary aldosteronism demonstrated an unilateral aldosterone producing adenoma that was surgically removed, with subsequent optimal blood pressure control with two anti-hypertensive drugs. In this case, the failure of the first screening prevented a correct diagnosis of primary aldosteronism, with consequent inadequate blood pressure control in following years and end organ damage. The case suggests the need of clinical follow-up and eventual reappraisal of patients showing a condition of refractory hypertension associated with hypokalemia despite a first negative screening test.

  4. A novel haplotype of low-frequency variants in the aldosterone synthase gene among northern Han Chinese with essential hypertension.

    Science.gov (United States)

    Zhang, Hao; Li, Xueyan; Zhou, Li; Zhang, Keyong; Zhang, Qi; Li, Jingping; Wang, Ningning; Jin, Ming; Wu, Nan; Cong, Mingyu; Qiu, Changchun

    2017-09-01

    Low-frequency variants showed that there is more power to detect risk variants than to detect protective variants in complex diseases. Aldosterone plays an important role in the renin-angiotensin-aldosterone system, and aldosterone synthase catalyzes the speed-controlled steps of aldosterone biosynthesis. Polymorphisms of the aldosterone synthase gene (CYP11B2) have been reported to be associated with essential hypertension (EH). CYP11B2 polymorphisms such as -344T/C, have been extensively reported, but others are less well known. This study aimed to assess the association between human CYP11B2 and EH using a haplotype-based case-control study. A total of 1024 EH patients and 956 normotensive controls, which consist of north Han population peasants, were enrolled. Seven single nucleotide polymorphisms (SNPs) (rs28659182, rs10087214, rs73715282, rs542092383, rs4543, rs28491316, and rs7463212) covering the entire human CYP11B2 gene were genotyped as markers using the MassARRAY system. The major allele G frequency of rs542092383 was found to be risk against hypertension [odds ratio (OR) 3.478, 95% confidence interval (95% CI) 1.407-8.597, P = .004]. The AG genotype frequency of SNP rs542092383 was significantly associated with an increased risk of hypertension (OR 4.513, 95% CI 1.426-14.287, P = .010). In the haplotype-based case-control analysis, the frequency of the T-G-T haplotype was higher for EH patients than for controls (OR 5.729, 95% CI 1.889-17.371, P = .000495). All |D'| values of the seven SNPs were >0.9, and r values for rs28659182- rs10087214-rs28491316-rs7463212 SNPs were >0.8 and showed strong linkage intensity. Haplotype T-G-T may therefore be a useful genetic marker for EH.

  5. The effect of oxygen on aldosterone release from bovine adrenocortical cells in vitro: PO2 versus steroidogenesis.

    Science.gov (United States)

    Raff, H; Kohandarvish, S

    1990-08-01

    Hypoxia decreases plasma aldosterone in vivo without a decrease in PRA, angiotensin II (ANG II), ACTH, or cortisol. The present study evaluated whether this could be due to a direct, specific inhibitory effect on the zona glomerulosa related to the magnitude of the decrease in oxygen (O2). Bovine adrenocortical cells were dispersed with collagenase and studied in vitro within 48 h. Cells were stimulated for 2 h with ANG II (0.1-1000 nM) or (Bu)2cAMP (0.3-3 mM) under oxygen levels ranging from 0 to 100% O2 (PO2 from 66 +/- 4 to 561 +/- 46 torr) vs. a reference gas mixture (21% O2 PO2 approximately 140 torr). Exposure to 123 +/- 8, 110 +/- 12, 100 +/- 16, and 66 +/- 4 torr led to 27%, 30%, 40% and 70% inhibition, respectively, of 3 nM ANG II-stimulated aldosterone secretion as compared to 140 +/- 16 torr (reference). Exposure to hyperoxia (288 +/- 36 to 561 +/- 46 torr) led to a small (10%) increase in ANG II-stimulated aldosterone secretion which was not statistically significant. The P50 (half-maximal PO2) for aldosteronogenesis was approximately 95 torr. The results for other doses of ANG II and for cAMP were similar. The inhibitory effect of low O2 was reversed by returning the cells to reference conditions (140 +/- 16 torr). Cortisol secretion was not significantly affected by changes in oxygen tension. We conclude that small changes in O2 within the physiological range directly and specifically inhibit aldosteronogenesis in a dose-dependent manner with a P50 of approximately 95 torr. Inhibition of cAMP-stimulated aldosterone secretion suggests a postreceptor site of action. This direct, reversible, and specific effect on the zona glomerulosa of the adrenal cortex may account for the dissociation of renin and aldosterone during hypoxia in vivo.

  6. [The effects of renin-angiotensin system blockade on the liver steatosis in rats on long-term high-fat diet].

    Science.gov (United States)

    Chen, Ying-Hua; Yuan, Li; Chen, Yuan-Yuan; Qi, Cui-Juan

    2008-03-01

    To observe the relationship between liver steatosis in rats with long-term high-caloric and high-fat diet and the expression of angiotensinogen (AGT), uncoupling protein 2 (UCP-2) and transforming growth factor beta1 (TGFbeta1). Then angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) drugs were given to investigate whether rennin-angiotensin system (RAS) blockade can mitigate the liver steatosis and to probe its mechanisms. Forty male Wistar rats were divided into normal control group (NC group, n = 10), high-calorie and high-fat fed group (HF group, n = 10), ARB treated group (AR group, n = 10) and ACEI treated group (AE group, n = 10). Rats were fed with high-calorie and high-fat diet and given RAS inhibitor drugs (valsartan 40 mg/kg to the AR group and perindopril 4 mg/kg to the AE group) for eight weeks. Serum TG, free fatty acids (FFAs) lever and the fat content in liver were then measured with biochemical tests; insulin resistance was evaluated with euglycemic hyperinsulinemia clamp technique, the expression of UCP-2 and TGFbeta1 in liver tissue were examined with immunohistochemical staining and AGT mRNA, UCP-2 mRNA and TGFbeta1 mRNA were tested with RT-PCR. With the administration of RAS inhibitor drugs, following changes were observed. The levels of TG and FFAs and the fat content in liver decreased (P liver steatosis, inflammation and fibrosis were mitigated. The levels of UCP-2 decreased by 36.5% (P liver injury of long term high-fat fed rats and have a protective effect on liver. The mechanism may be associated with the effects of improved insulin resistance, the interaction within RAS and the down-regulation of UCP-2 and TGFbeta1 in liver tissue.

  7. Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited.

    Science.gov (United States)

    Rossier, Bernard C; Baker, Michael E; Studer, Romain A

    2015-01-01

    Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  8. Changes of serum aldosterone levels in patients with different stages of chronic renal insufficiency

    International Nuclear Information System (INIS)

    Zou Jun; Du Xueliang; Jiang Gengru

    2005-01-01

    Objective: To study the correlationship between the serum aldosterone levels and different stages of chronic renal insufficiency. Methods: Plasma renin activity (PRA), serum angiotensin II (Ang II) contents and serum aldosterone concentration (SACs) were determined with RIA in 42 patients with chronic renal insufficiency from various causes. The patients were divided into three groups according to their endogenous creatinine clearance rate: Group 1, (n=14) Ccr≥60ml/(min·1.73m 2 ); Group 2, (n =13) 20ml/(min·1.73m 2 ) ≤Ccr 2 ); Group 3, (n=15) Ccr 2 ). Results: The SACs values in Group 3 patients were significantly higher than those in Group 1 and Group 2 patients (P<0.01). The SACs values in Group 2 patients were also significantly higher than those in Group 1 patients (P<0.05). Ccr values were higher negatively correlated with the SACs values (r= -0.685, P<0.001). Conclusion: As the creatine clearance rate gradually deteriorated, the SACs values increased correspondingly in patients with chronic renal insufficiency from various causes. (authors)

  9. Dietary sodium deprivation evokes activation of brain regional neurons and down-regulation of angiotensin II type 1 receptor and angiotensin-convertion enzyme mRNA expression.

    Science.gov (United States)

    Lu, B; Yang, X J; Chen, K; Yang, D J; Yan, J Q

    2009-12-15

    Previous studies have indicated that the renin-angiotensin-aldosterone system (RAAS) is implicated in the induction of sodium appetite in rats and that different dietary sodium intakes influence the mRNA expression of central and peripheral RAAS components. To determine whether dietary sodium deprivation activates regional brain neurons related to sodium appetite, and changes their gene expression of RAAS components of rats, the present study examined the c-Fos expression after chronic exposure to low sodium diet, and determined the relationship between plasma and brain angiotensin I (ANG I), angiotensin II (ANG II) and aldosterone (ALD) levels and the sodium ingestive behavior variations, as well as the effects of prolonged dietary sodium deprivation on ANG II type 1 (AT1) and ANG II type 2 (AT2) receptors and angiotensin-convertion enzyme (ACE) mRNA levels in the involved brain regions using the method of real-time polymerase chain reaction (PCR). Results showed that the Fos immunoreactivity (Fos-ir) expression in forebrain areas such as subfornical organ (SFO), paraventricular hypothalamic nuclei (PVN), supraoptic nucleus (SON) and organum vasculosum laminae terminalis (OVLT) all increased significantly and that the levels of ANG I, ANG II and ALD also increased in plasma and forebrain in rats fed with low sodium diet. In contrast, AT1, ACE mRNA in PVN, SON and OVLT decreased significantly in dietary sodium depleted rats, while AT2 mRNA expression did not change in the examined areas. These results suggest that many brain areas are activated by increased levels of plasma and/or brain ANG II and ALD, which underlies the elevated preference for hypertonic salt solution after prolonged exposure to low sodium diet, and that the regional AT1 and ACE mRNA are down-regulated after dietary sodium deprivation, which may be mediated by increased ANG II in plasma and/or brain tissue.

  10. 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

  11. Angiotensin Converting Enzyme Inhibitor Has a Protective Effect on Decompression Sickness in Rats

    Directory of Open Access Journals (Sweden)

    Aleksandra Mazur

    2018-03-01

    Full Text Available Introduction: Commercial divers, high altitude pilots, and astronauts are exposed to some inherent risk of decompression sickness (DCS, though the mechanisms that trigger are still unclear. It has been previously showed that diving may induce increased levels of serum angiotensin converting enzyme. The renin angiotensin aldosterone system (RAAS is one of the most important regulators of blood pressure and fluid volume. The purpose of the present study was to control the influence of angiotensin II on the appearance of DCS.Methods: Sprague Dawley rats have been pre-treated with inhibitor of angiotensin II receptor type 1 (losartan; 10 mg/kg, angiotensin-converting enzyme (ACE inhibitor (enalapril; 10 mg/kg, and calcium-entry blocker (nifedipine; 20 mg/kg. The experimental groups were treated for 4 weeks before exposure to hyperbaric pressure while controls were not treated. Seventy-five rats were subjected to a simulated dive at 1000 kPa absolute pressure for 45 min before starting decompression. Clinical assessment took place over a period of 60 min after surfacing. Blood samples were collected for measurements of TBARS, interleukin 6 (IL-6, angiotensin II (ANG II and ACE.Results: The diving protocol induced 60% DCS in non-treated animals. This ratio was significantly decreased after treatment with enalapril, but not other vasoactive drugs. Enalapril did not change ANG II or ACE concentration, while losartant decreased post dive level of ACE but not ANG II. None of the treatment modified the effect of diving on TBARS and IL-6 values.Conclusion: Results suggests that the rennin angiotensin system is involved in a process of triggering DCS but this has to be further investigated. However, a vasorelaxation mediated process, which potentially could increase the load of inert gas during hyperbaric exposure, and antioxidant properties were excluded by our results.

  12. Effects of cilostazol and renin-angiotensin system (RAS) blockers on the renal disease progression of Korean patients: a retrospective cohort study.

    Science.gov (United States)

    Noh, Yoojin; Lee, Jimin; Shin, Sooyoung; Park, Inwhee; Bae, Soo Kyung; Oh, Euichul; Lee, Sukhyang

    2018-02-01

    Background Decline in estimated glomerular filtration rate (eGFR) is an important surrogate marker for the assessment of renal function. Addition of a second agent to angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) treatment may improve current therapeutic strategies aimed at suppressing renal disease progression. Objective To determine the effect of cilostazol in combination with ACEI or ARB treatment on the decline in eGFR. Setting A tertiary hospital in Korea. Method In an observational cohort study, we analyzed 5505 patients who were prescribed ACEI or ARB and cilostazol or other antiplatelet agents. Main outcome measure The primary outcome assessed was worsening of renal function defined as a 30% decline in eGFR per year. The secondary outcomes included commencement of dialysis, renal transplantation, death, myocardial infarction, and ischemic stroke. Results Following propensity score matching, eGFR decreased over time in the majority of patients, but the decline was less in patients in the cilostazol treated (CT) group of stage 1-2 category compared to the cilostazol untreated (CU) group (OR 0.80; 95% CI 0.66-0.98). In the subgroup analysis, the strongest effect in slowing eGFR decline was observed in CT patients at a high risk of diabetes (OR 0.782; 95% CI 0.615-0.993) and the elderly (OR 0.693; 95% CI 0.504-0.953) in the stage 1-2 category. No significant increase in cardiovascular risk was observed between the CT and CU groups. Conclusion Treatment with cilostazol plus ACEI or ARB was observed to prevent worsening of renal progression in patients in the stages 1-2.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Effects of angiotensin II blockade on intermediate cardiovascular endpoints in haemodialysis patients: a randomised double-blind placebo-controlled one-year intervention trial (SAFIR study)

    DEFF Research Database (Denmark)

    Peters, Christian Daugaard; Kjærgaard, Krista Dybtved; Jensen, Jens Dam

    Agents blocking the renin-angiotensin-aldosterone system are frequently used in end-stage renal disease patients, but whether they exert beneficial cardiovascular (CV) effects is unclear. The long-term effects of the angiotensin II receptor blocker irbesartan was investigated in 82 haemodialysis...... renal function. Brachial BP decreased significantly in both groups, but there was no significant difference between placebo and irbesartan treated. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different in the two groups. Intermediate CV endpoints...... such as central aortic BP, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal prohormone of brain natriuretic peptide, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic BP during the study period correlated...

  15. Leptin-Aldosterone-Neprilysin Axis: Identification of Its Distinctive Role in the Pathogenesis of the Three Phenotypes of Heart Failure in People With Obesity.

    Science.gov (United States)

    Packer, Milton

    2018-04-10

    Obesity (especially visceral adiposity) can be associated with 3 different phenotypes of heart failure: heart failure with a reduced ejection fraction, heart failure with a preserved ejection fraction, and high-output heart failure. All 3 phenotypes are characterized by an excessive secretion of aldosterone and sodium retention. In addition, obesity is accompanied by increased signaling through the leptin receptor, which can promote activation of both the sympathetic nervous system and the renin-angiotensin system and can directly stimulate the secretion of aldosterone. The deleterious interaction of leptin and aldosterone is potentiated by the simultaneous action of adiposity and the renal sympathetic nerves to cause overactivity of neprilysin; the loss of the counterbalancing effects of natriuretic peptides is exacerbated by an additional effect of both obesity and heart failure to interfere with adiponectin signaling. This intricate neurohormonal interplay leads to plasma volume expansion as well as to adverse ventricular remodeling and cardiac fibrosis. Furthermore, the activity of aldosterone and neprilysin is not only enhanced by obesity, but these mechanisms can also promote adipogenesis and adipocyte dysfunction, thereby enhancing the positive feedback loop. Last, in elderly obese women, changes in quantity and biology of epicardial adipose tissue further enhances the release of leptin and other proinflammatory adipokines, thereby leading to cardiac and systemic inflammation, end-organ fibrosis, and multiple comorbidities. Regardless of the phenotypic expression, activation of the leptin-aldosterone-neprilysin axis appears to contribute importantly to the evolution and progression of heart failure in people with obesity. Efforts to interfere with the detrimental interactions of this distinctive neurohormonal ecosystem with existing or novel therapeutic agents are likely to yield unique clinical benefits. © 2018 American Heart Association, Inc.

  16. Effect of calcium channels blockers and inhibitors of the renin-angiotensin system on renal outcomes and mortality in patients suffering from chronic kidney disease: systematic review and meta-analysis.

    Science.gov (United States)

    Zhao, Hong-Jin; Li, Yan; Liu, Shan-Mei; Sun, Xiang-Guo; Li, Min; Hao, Yan; Cui, Lian-Qun; Wang, Ai-Hong

    2016-07-01

    The renoprotective effect of inhibitors of renin-angiotensin system (RAS) has been identified through placebo-controlled trials. However, the effect of calcium-channel blockers (CCBs) on renal system is still controversial. Our current meta-analysis includes available evidences to compare the effect of dihydropyridine CCBs and ACEIs or ARBs on renal outcomes and mortality. We also further investigate whether CCBs can be used in combination with inhibitors of RAS to improve the prognosis of patients with chronic kidney disease (CKD). Electronic databases were searched up to July 2012, for clinical randomized controlled trials, assessing the effect of dihydropyridine CCBs on the incidence of end-stage renal disease (ESRD) and all-cause mortality in contrast to ACEIs or ARBs. Eight clinical trials were included containing 25,647 participants. ESRD showed significantly higher frequency with CCBs therapy compared with ACEIs or ARBs therapy, though blood pressure was decreased similarly in both groups in every trial (OR, 1.25; 95% CI, 1.05-1.48; p = 0.01). In contrast, there was no significant difference in the incidence of all-cause mortality between these two groups, though ACEIs or ARBs exhibited better renoprotective effect compared to CCBs (OR, 0.96; 95% CI, 0.89-1.03; p = 0.24). CCBs did not increase all-cause mortality incidence in patients with CKD though they displayed weaker renoprotective, compared to ACEIs or ARBs therapy. Our results suggest the combination of a CCB and an ACEI or ARB should be a preferable antihypertensive therapy in patients with CKD, considering their higher effect in decreasing blood pressure and fewer adverse metabolic problems caused.

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

    Science.gov (United States)

    Erdmann, Erland; Spanheimer, Robert; Charbonnel, Bernard

    2010-09-01

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

  18. Aldosterone synthase gene is not a major susceptibility gene for progression of chronic kidney disease in patients with autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Gnanasambandan Ramanathan

    2017-01-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is the most common heritable kidney disease and is characterized by bilateral renal cysts. Hypertension is a frequent cause of chronic kidney disease (CKD and mortality in patients with ADPKD. The aldosterone synthase gene polymorphisms of the renin-angiotensin-aldosterone system have been extensively studied as hypertension candidate genes. The present study is aimed to investigate the potential modifier effect of CYP11B2 gene on the progression of CKD in ADPKD. One hundred and two ADPKD patients and 106 healthy controls were recruited based on Ravine inclusion and exclusion criteria. The three tag-SNPs within CYP11B2 gene (rs3802230, rs4543, and rs4544 were genotyped using FRET-based KASPar method. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Mantel- Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms. Of the three tag-SNPs genotyped, rs4544 polymorphism was monomorphic and rs3802230 deviated Hardy-Weinberg equilibrium. The CYP11B2 tag-SNPs did not show significant association with ADPKD or CKD. Further, these polymorphisms did not exhibit confounding effect on the relationship between CKD progression and hypertension. Our results suggest that aldosterone synthase gene is not a major susceptibility gene for progression of CKD in South Indian ADPKD patients.

  19. Renin blood test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003698.htm Renin blood test To use the sharing features on this page, ... renin test measures the level of renin in blood. How the Test is Performed A blood sample is needed . How ...

  20. Differential control of MMP and t-PA/PAI-1 expressions by sympathetic and renin-angiotensin systems in rat left ventricle.

    Science.gov (United States)

    Dab, Houcine; Hachani, Rafik; Hodroj, Wassim; Sakly, Mohsen; Bricca, Giampiero; Kacem, Kamel

    2009-10-05

    In the present study, we tested the hypothesis that angiotensin II (Ang II) has both direct (via AT1 receptors) and indirect (via sympathostimulator pathway) actions on the synthesis and activity of the enzymes involved in the extracellular matrix degradation in vivo. For this purpose, sympathectomy and blockade of the Ang II receptor AT1 were performed alone or in combination in normotensive rats. The mRNA of the plasminogen activator (t-PA) and its inhibitor (PAI-1), the mRNA, protein and activity of the matrix metalloproteinases MMP-2 and MMP-9 were examined by Q-RT-PCR, immunoblotting and zymographic methods in the left ventricle. t-PA and PAI-1 mRNA were decreased after sympathectomy and remained unchanged after AT1 receptors blockade. mRNA was increased for t-PA and decreased by similar degree for PAI-1 after double treatment. MMPs mRNA and protein levels were decreased either after sympathectomy or AT1 receptors blockade and an additive effect was acquired after double treatment. MMPs activity was decreased by similar degree in the three treated groups. Deducted interpretations from our experimental approach suggest that Ang II inhibits directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) t-PA mRNA synthesis. It seems unable to influence directly PAI-1 mRNA, but stimulates indirectly PAI-1 mRNA synthesis. Ang II stimulates directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) MMPs synthesis at both transcriptional and protein levels. The enzymatic activity of MMPs does not seem to be influenced directly by Ang II but it could be stimulated indirectly (via sympathostimulator pathway).

  1. Adherence to guidelines for creatinine and potassium monitoring and discontinuation following renin-angiotensin system blockade: a UK general practice-based cohort study.

    Science.gov (United States)

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

    2017-01-09

    To examine adherence to serum creatinine and potassium monitoring and discontinuation guidelines following initiation of treatment with ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs); and whether high-risk patients are monitored. A general practice-based cohort study using electronic health records from the UK Clinical Practice Research Datalink and Hospital Episode Statistics. UK primary care, 2004-2014. 223 814 new ACEI/ARB users. Proportion of patients with renal function monitoring before and after ACEI/ARB initiation; creatinine increase ≥30% or potassium levels >6 mmol/L at first follow-up monitoring; and treatment discontinuation after such changes. Using logistic regression models, we also examined patient characteristics associated with these biochemical changes, and with follow-up monitoring within the guideline recommendation of 2 weeks after treatment initiation. 10% of patients had neither baseline nor follow-up monitoring of creatinine within 12 months before and 2 months after initiation of an ACEI/ARB, 28% had monitoring only at baseline, 15% only at follow-up, and 47% both at baseline and follow-up. The median period between the most recent baseline monitoring and drug initiation was 40 days (IQR 12-125 days). 34% of patients had baseline creatinine monitoring within 1 month before initiating therapy, but creatinine increase ≥30% (n=567, 1.2%) or potassium level >6 mmol/L (n=191, 0.4%), 80% continued treatment. Although patients with prior myocardial infarction, hypertension or baseline potassium >5 mmol/L were at high risk of ≥30% increase in creatinine after ACEI/ARB initiation, there was no evidence that they were more frequently monitored. Only one-tenth of patients initiating ACEI/ARB therapy receive the guideline-recommended creatinine monitoring. Moreover, the vast majority of the patients fulfilling postinitiation discontinuation criteria for creatinine and potassium increases continue on treatment

  2. Dual Angiotensin Receptor and Neprilysin Inhibition with Sacubitril/Valsartan in Chronic Systolic Heart Failure: Understanding the New PARADIGM.

    Science.gov (United States)

    Lillyblad, Matthew P

    2015-11-01

    To evaluate the clinical role of sacubitril/valsartan, a novel angiotensin-neprilysin inhibitor, for the treatment of chronic heart failure with a reduced ejection fraction (HFrEF). A search of PubMed was conducted using a combination of the search terms sacubitril, valsartan, LCZ696, neprilysin inhibition, natriuretic peptide system, renin-angiotensin system, and heart failure with reduced ejection fraction. Bibliographies of all retrieved articles were reviewed for relevant literature. All references included were published between 1980 and May 2015. All studies and review articles that contained data describing the use of sacubitril/valsartan in HFrEF were reviewed. HFrEF remains a disease of high morbidity and mortality. Natriuretic peptide (NP) augmentation has emerged as a most promising neurohormonal target in HFrEF. NPs provide vasodilatory, natriuretic, diuretic, and antiproliferative actions to help support the failing heart. Neprilysin, a neutral endopeptidase, is a primary pathway for NP metabolism. Combined inhibition of the renin angiotensin aldosterone system and neprilysin augments the beneficial natriuretic peptide pathway while providing direct antagonism to increases in angiotensin II. In the landmark PARADIGM HF trial, the neprilysin inhibitor sacubitril added to valsartan significantly improved morbidity and mortality over enalapril, a standard of care in HFrEF. Application of these results to clinical practice requires careful considerations of trial design, study patient population, and clinical monitoring. Sacubitril/valsartan significantly improved morbidity and mortality in patients with chronic HFrEF but will require careful application to "real-world" populations of HFrEF. © The Author(s) 2015.

  3. Circulating aldosterone induces the apical accumulation of the proton pumping V-ATPase and increases proton secretion in clear cells in the caput epididymis.

    Science.gov (United States)

    Roy, Jeremy W; Hill, Eric; Ruan, Ye Chun; Vedovelli, Luca; Păunescu, Teodor G; Brown, Dennis; Breton, Sylvie

    2013-08-15

    Clear cells express the vacuolar proton-pumping H(+)-ATPase (V-ATPase) and acidify the lumen of the epididymis, a process that is essential for male fertility. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance in the epididymis, and a previous study showed binding of aldosterone exclusively to epididymal clear cells (Hinton BT, Keefer DA. Steroid Biochem 23: 231-233, 1985). We examined here the role of aldosterone in the regulation of V-ATPase in the epididymis. RT-PCR showed expression of the mineralocorticoid receptor [MR; nuclear receptor subfamily 3, group C member 2 (NR3C2)] and 11-β-dehydrogenase isozyme 2 (HSD11β2) mRNAs specifically in clear cells, isolated by fluorescence-activated cell sorting from B1-enhanced green fluorescent protein (EGFP) mice. Tail vein injection of adult rats with aldosterone, 1,2-dioctanoyl-sn-glycerol (DOG), or 8-(4-chlorophenylthio)-cAMP (cpt-cAMP) induced V-ATPase apical membrane accumulation and extension of V-ATPase-labeled microvilli in clear cells in the caput epididymis but not in the cauda. V-ATPase activity was measured in EGFP-expressing clear cells using the intracellular pH (pHi)-sensing dye seminaphthorhodafluor-5F-5-(and 6)-carboxylic acid, acetoxymethyl ester acetate (SNARF-5F). Aldosterone induced a rapid increase in the rate of Na(+)- and bicarbonate-independent pHi recovery following an NH4Cl-induced acid load in clear cells isolated from the caput but not the cauda. This effect was abolished by concanamycin A, spironolactone, and chelerythrine but not myristoylated-protein kinase inhibitor (mPKI) or mifepristone. Thus aldosterone increases V-ATPase-dependent proton secretion in clear cells in the caput epididymis via MR/NR3C2 and PKC activation. This study, therefore, identifies aldosterone as an active member of the RAAS for the regulation of luminal acidification in the proximal epididymis.

  4. The studies on aldosterone secretion rate by radioimmunoassay

    International Nuclear Information System (INIS)

    Takenouchi, Takahiko

    1974-01-01

    The aldosterone secretion rate was measured by radioimmunoassay in 12 normal subjects and 47 hypertensive patients. The values ranged from 25.0 to 60.2 ng/day with a mean of 39.6+-10.7 (S.D.) in 8 normal males and from 30.2 to 85.4 ng/day with a mean of 62.6+-26.8 (S.D.) in 4 normal females. The mean value in 21 cases with benign essential hypertension was found to be within normal range. No significant difference was found in the aldosterone secretion rate between the group of benign essential hypertension with suppressed renin activity and with nonsuppressed renin activity. Metabolic clearance rate in benign essential hypertension was observed to be within normal range. The aldosterone secretion rate in a few cases of benign essential hypertension failed to increase normally in response to sodium restriction (<50 mEq/day). The values in 11 cases of primary aldosteronism were found to be clearly higher, when compared with the values of normal subjects and subjects with benign essential hypertension. High values were found in patients suffering from malignant hypertension and in 3 with unilateral renal artery stenosis. The values in cases of bilateral renal artery stenosis, of pheochromocytoma, and of acromegaly with hypertension were within normal range. Low values in the aldosterone secretion rate were found in 3 cases each of 17α-hydroxylase deficiency and Cushing's syndrome. (JPN)

  5. Expression and nutritional regulation of the (pro)renin receptor in rat visceral adipose tissue.

    Science.gov (United States)

    Achard, V; Tassistro, V; Boullu-Ciocca, S; Grino, M

    2011-12-01

    Early life nutritional environment plays an important role in the development of visceral adipose tissue and interacts with nutritional regulations in adulthood, leading to metabolic dysregulations. We hypothesized that the renin-angiotensin system may play a role in the programming-induced development of visceral adipose tissue. We studied, using a model of programming of overweight and glucose intolerance, obtained by post-natal overfeeding with consecutive highfat diet, the status of plasma renin activity and mesenteric adipose renin-angiotensin system, including the recently identified (pro)renin receptor, in adult rats. Post-natal overfeeding or high-fat feeding lead to overweight with increased visceral fat mass and adipocytes surface. When both paradigms were associated, adipocytes surface showed a disproportionate increase. A strong immunoreactivity for (pro)renin receptor was found in stromal cells. Plasma renin activity increased in programmed animals whereas (pro)renin receptor expressing cells density was stimulated by high-fat diet. There was a positive, linear relationship between plasma renin activity and (pro)renin receptor expressing cells density and adipocytes surface. Our experiments demonstrate that association of post-natal overfeeding and high-fat diet increased plasma renin activity and adipose (pro)renin receptor expression. Such phenomenon could explain, at least in part, the associated disproportionate adipocyte hypertrophy and its accompanying increased glucose intolerance.

  6. Atrial distension, haemodilution, and acute control of renin release during water immersion in humans

    DEFF Research Database (Denmark)

    Gabrielsen, A; Pump, B; Bie, P

    2002-01-01

    immersion. During WI, central venous pressure (CVP) and left atrial diameter (LAD) increased (P ... is not the single pivotal stimulus for the acute suppression of renin release in response to intravascular volume expansion by water immersion in humans. Haemodilution constitutes a significant and conceivably the principal stimulus for the acute immersion-induced suppression of renin-angiotensin system activity....

  7. Aldosterone and aldosterone receptor antagonists in patients with chronic heart failure

    Directory of Open Access Journals (Sweden)

    Nappi J

    2011-06-01

    associated with systolic heart failure will benefit from the addition of an aldosterone receptor antagonist to the standard therapies of angiotensin-converting enzyme inhibitors and beta-blockers. This review will address the pharmacologic basis of aldosterone receptor antagonists in patients with heart failure and the clinical impact of this therapy.Keywords: aldosterone receptor antagonists, eplerenone, spironolactone, systolic heart failure

  8. 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

    2017-10-01

    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.

  9. IN SILICO EVALUATION OF ANGIOTENSIN II RECEPTOR ANTAGONIST’S PLASMA PROTEIN BINDING USING COMPUTED MOLECULAR DESCRIPTORS

    Directory of Open Access Journals (Sweden)

    Jadranka Odović

    2014-03-01

    Full Text Available The discovery of new pharmacologically active substances and drugs modeling led to necessity of predicting drugs properties and its ADME data. Angiotensin II receptor antagonists are a group of pharmaceuticals which modulate the renin-angiotensin-aldosterone system and today represent the most commonly prescribed anti-hypertensive drugs. The aim of this study was to compare different molecular properties of seven angiotensin II receptor antagonists / blockers (ARBs, (eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan and their plasma protein binding (PPB data. Several ARBs molecular descriptors were calculated using software package Molinspiration Depiction Software as well as Virtual Computational Chemistry Laboratory (electronic descriptor – PSA, constitutional parameter – Mw, geometric descriptor – Vol, lipophilicity descriptors - logP values, aqueous solubility data – logS. The correlations between all collected descriptors and plasma protein binding data obtained from relevant literature were established. In the simple linear regression poor correlations were obtained in relationships between PPB data and all calculated molecular descriptors. In the next stage of the study multiple linear regression (MLR was used for correlation of PPB data with two different descriptors as independent variables. The best correlation (R2=0.70 with P<0.05 was established between PPB data and molecular weight with addition of volume values as independent variables. The possible application of computed molecular descriptors in drugs protein binding evaluation can be of great importance in drug research.

  10. Predominance of AT1 Blockade Over Mas–Mediated Angiotensin-(1–7) Mechanisms in the Regulation of Blood Pressure and Renin–Angiotensin System in mRen2.Lewis Rats

    Science.gov (United States)

    2013-01-01

    BACKGROUND We investigated whether the antihypertensive actions of the angiotensin II (Ang II) receptor (AT1-R) blocker, olmesartan medoxomil, may in part be mediated by increased Ang-(1–7) in the absence of significant changes in plasma Ang II. METHODS mRen2.Lewis congenic hypertensive rats were administered either a vehicle (n = 14) or olmesartan (0.5mg/kg/day; n = 14) by osmotic minipumps. Two weeks later, rats from both groups were further randomized to receive either the mas receptor antagonist A-779 (0.5mg/kg/day; n = 7 per group) or its vehicle (n = 7 per group) for the next 4 weeks. Blood pressure was monitored by telemetry, and circulating and tissue components of the renin–angiotensin system (RAS) were measured at the completion of the experiments. RESULTS Antihypertensive effects of olmesartan were associated with an increase in plasma renin concentration, plasma Ang I, Ang II, and Ang-(1–7), whereas serum aldosterone levels and kidney Ang II content were reduced. Preserved Ang-(1–7) content in kidneys was associated with increases of ACE2 protein but not activity and no changes on serum and kidney ACE activity. There was no change in cardiac peptide levels after olmesartan treatment. The antihypertensive effects of olmesartan were not altered by concomitant administration of the Ang-(1–7) receptor antagonist except for a mild further increase in plasma renin concentration. CONCLUSIONS Our study highlights the independent regulation of RAS among plasma, heart, and kidney tissue in response to AT1-R blockade. Ang-(1–7) through the mas receptor does not mediate long-term effects of olmesartan besides counterbalancing renin release in response to AT1-R blockade. PMID:23459599

  11. The catalytic mechanism of mouse renin studied with QM/MM calculations.

    Science.gov (United States)

    Brás, Natércia F; Ramos, Maria J; Fernandes, Pedro A

    2012-09-28

    Hypertension is a chronic condition that affects nearly 25% of adults worldwide. As the Renin-Angiotensin-Aldosterone System is implicated in the control of blood pressure and body fluid homeostasis, its combined blockage is an attractive therapeutic strategy currently in use for the treatment of several cardiovascular conditions. We have performed QM/MM calculations to study the mouse renin catalytic mechanism in atomistic detail, using the N-terminal His6-Asn14 segment of angiotensinogen as substrate. The enzymatic reaction (hydrolysis of the peptidic bond between residues in the 10th and 11th positions) occurs through a general acid/base mechanism and, surprisingly, it is characterized by three mechanistic steps: it begins with the creation of a first very stable tetrahedral gem-diol intermediate, followed by protonation of the peptidic bond nitrogen, giving rise to a second intermediate. In a final step the peptidic bond is completely cleaved and both gem-diol hydroxyl protons are transferred to the catalytic dyad (Asp32 and Asp215). The final reaction products are two separate peptides with carboxylic acid and amine extremities. The activation energy for the formation of the gem-diol intermediate was calculated as 23.68 kcal mol(-1), whereas for the other steps the values were 15.51 kcal mol(-1) and 14.40 kcal mol(-1), respectively. The rate limiting states were the reactants and the first transition state. The associated barrier (23.68 kcal mol(-1)) is close to the experimental values for the angiotensinogen substrate (19.6 kcal mol(-1)). We have also tested the influence of the density functional on the activation and reaction energies. All eight density functionals tested (B3LYP, B3LYP-D3, X3LYP, M06, B1B95, BMK, mPWB1K and B2PLYP) gave very similar results.

  12. Characterization of renin mRNA expression and enzyme activity in rat and mouse mesangial cells

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    Andrade A.Q.

    2002-01-01

    Full Text Available Renin is an enzyme involved in the stepwise generation of angiotensin II. Juxtaglomerular cells are the main source of plasma renin, but renin activity has been detected in other cell types. In the present study we evaluated the presence of renin mRNA in adult male Wistar rat and mouse (C-57 Black/6 mesangial cells (MC and their ability to process, store and release both the active and inactive forms of the enzyme. Active renin and total renin content obtained after trypsin treatment were estimated by angiotensinogen consumption analyzed by SDS-PAGE electrophoresis and quantified by angiotensin I generation by HPLC. Renin mRNA, detected by RT-PCR, was present in both rat and mouse MC under basal conditions. Active renin was significantly higher (P<0.05 in the cell lysate (43.5 ± 5.7 ng h-1 10(6 cells than in the culture medium (12.5 ± 2.5 ng h-1 10(6 cells. Inactive prorenin content was similar for the intra- and extracellular compartments (9.7 ± 3.1 and 3.9 ± 0.9 ng h-1 10(6 cells. Free active renin was the predominant form found in both cell compartments. These results indicate that MC in culture are able to synthesize and translate renin mRNA probably as inactive prorenin which is mostly processed to active renin inside the cell. MC secrete both forms of the enzyme but at a lower level compared with intracellular content, suggesting that the main role of renin synthesized by MC may be the intracellular generation of angiotensin II.

  13. Angiotensin type 2 receptor (AT2R) and receptor Mas

    DEFF Research Database (Denmark)

    Villela, Daniel; Leonhardt, Julia; Patel, Neal

    2015-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striki...

  14. The aldo-keto reductase AKR1B7 coexpresses with renin without influencing renin production and secretion.

    Science.gov (United States)

    Machura, Katharina; Iankilevitch, Elina; Neubauer, Björn; Theuring, Franz; Kurtz, Armin

    2013-03-01

    On the basis of evidence that within the adult kidney, the aldo-keto reductase AKR1B7 (aldo-keto reductase family 1, member 7, also known as mouse vas deferens protein, MVDP) is selectively expressed in renin-producing cells, we aimed to define a possible role of AKR1B7 for the regulation and function of renin cells in the kidney. We could confirm colocalization and corecruitment of renin and of AKR1B7 in wild-type kidneys. Renin cells in AKR1B7-deficient kidneys showed normal morphology, numbers, and intrarenal distribution. Plasma renin concentration (PRC) and renin mRNA levels of AKR1B7-deficient mice were normal at standard chow and were lowered by a high-salt diet directly comparable to wild-type mice. Treatment with a low-salt diet in combination with an angiotensin-converting enzyme inhibitor strongly increased PRC and renin mRNA in a similar fashion both in AKR1B7-deficient and wild-type mice. Under this condition, we also observed a strong retrograde recruitment of renin-expressing cell along the preglomerular vessels, however, without a difference between AKR1B7-deficient and wild-type mice. The isolated perfused mouse kidney model was used to study the acute regulation of renin secretion by ANG II and by perfusion pressure. Regarding these parameters, no differences were observed between AKR1B7-deficient and wild-type kidneys. In summary, our data suggest that AKR1B7 is not of major relevance for the regulation of renin production and secretion in spite of its striking coregulation with renin expression.

  15. Chronic blockade of angiotensin II action prevents glomerulosclerosis, but induces graft vasculopathy in experimental kidney transplantation

    NARCIS (Netherlands)

    Smit-van Oosten, A; Navis, G; Stegeman, CA; Joles, JA; Klok, PA; Kuipers, F; Tiebosch, ATMG; van Goor, H

    Long-term renin-angiotensin system blockade is beneficial in a variety of renal diseases, This study examines the long-term (34 weeks) effects of the angiotensin-converting enzyme inhibitor lisinopril and the angiotensin II receptor type I blocker L158,809 in the Fisher to Lewis rat model of chronic

  16. No effect of angiotensin II AT(2)-receptor antagonist PD 123319 on cerebral blood flow autoregulation

    DEFF Research Database (Denmark)

    Estrup, T M; Paulson, O B; Strandgaard, S

    2001-01-01

    Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin AT1-receptor antagonists shift the limits of autoregulation of cerebral blood flow (CBF) towards lower blood pressure (BP). The role of AT2-receptors in the regulation of the cerebral cir...

  17. Recurrence of primary aldosteronism after percutaneous ethanol injection

    Directory of Open Access Journals (Sweden)

    Fan-Chi Chang

    2012-03-01

    Full Text Available Adrenalectomy is the definite treatment for aldosterone-producing adenoma (APA. Percutaneous ethanol or acetic acid injection with computed tomography (CT guidance has been described as a safe, noninvasive, and effective alternative treatment modality in patients with high surgical risk. We report on a man who was 49 years of age and presented with treatment-resistant hypertension and was later diagnosed with APA. CT-guided percutaneous ethanol injection (PEI was performed for this high surgical risk patient. He had aldosteronism recurrence 4 years after the ethanol injection, so a second PEI was performed. The tumor size was reduced and his blood pressure was normalized. Therefore, we suggest that clinicians should closely check aldosterone to renin ration and potassium level if percutaneous chemical ablation is considered in functioning adrenal adenomas.

  18. The influence of certain molecular descriptors of fecal elimination of angiotensin II receptor antagonists

    Directory of Open Access Journals (Sweden)

    Trbojević-Stanković Jasna B.

    2015-01-01

    Full Text Available Angiotensin II receptor antagonists (ARBs modulate the function of the renin-angiotensin-aldosterone system and are commonly prescribed antihypertensive drugs, especially in patients with renal failure. In this study, the relationship between several molecular properties of seven ARBs (candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan and their fecal elimination data obtained from the literature were investigated. The ARB molecular descriptors were calculated using three software packages. Simple linear regression analysis showed the best 2 correlation between fecal elimination data and lipophilicity descriptor, ClogP values (R2 = 0.725. Multiple linear regression was applied to examine the correlation of ARBs’ fecal elimination data with their lipophilicity and one additional, calculated descriptor. The best correlation (R2 = 0.909 with an acceptable probability value, P <0.05 was established between the ARB fecal elimination data and their lipophilicity and aqueous solubility data. Applying computed molecular descriptors for evaluating drug elimination is of great importance in drug research.

  19. The Evaluation of Angiotensin-Converting Enzyme Inhibitors in Renal Elimination with Selected Molecular Descriptors

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    Trbojevic Jovana

    2017-06-01

    Full Text Available Angiotensin-converting enzyme (ACE inhibitors modulate the function of the renin-angiotensin-aldosterone system, and they are commonly prescribed antihypertensive drugs especially in patients with renal failure. In this study, the relationships between several molecular properties of eight ACE inhibitors (enalapril, quinapril, fosinopril, ramipril, benazepril, perindopril, moexipril, trandolapril and their renal elimination data, from relevant literature, were investigated. The ’molecular descriptors of the ACE inhibitors, which included aqueous solubility data (logS; an electronic descriptor, polar surface area (PSA;, a constitutional parameter, molecular mass (Mr; and a geometric descriptor, volume value (Vol, as well as lipophilicity descriptors (logP values, were calculated using different software packages. Simple linear regression analysis showed the best correlation between renal elimination data and lipophilicity descriptor AClogP values (R2 = 0.5742. In the next stage of the study, multiple linear regression was applied to assess a higher correlation between the ACE inhibitors’ renal elimination data and lipophilicity, AClogP, with one additional descriptor as an independent variable. Good correlations were established between renal elimination data from the literature and the AClogP lipophilicity descriptor using the constitutional parameter (molecular mass (R2 = 0.7425 or the geometric descriptor (volume value (R2 = 0.7224 as an independent variable. The application of computed molecular descriptors in evaluating drug elimination is of great importance in drug research.

  20. Macrolides for KCNJ5-mutated aldosterone-producing adenoma (MAPA): design of a study for personalized diagnosis of primary aldosteronism.

    Science.gov (United States)

    Maiolino, Giuseppe; Ceolotto, Giulio; Battistel, Michele; Barbiero, Giulio; Cesari, Maurizio; Amar, Laurence; Caroccia, Brasilina; Padrini, Roberto; Azizi, Michel; Rossi, Gian Paolo

    2018-02-06

    Aldosterone-producing adenoma (APA) is the main curable cause of endocrine hypertension cause of primary aldosteronism (PA) and it is in up to 66% of all cases investigated with adrenal vein sampling (AVS). Mutations in the KCNJ5 potassium channel involve up to 70% of APA and cause the most florid PA phenotypes. The recent finding that macrolide antibiotics specifically inhibit in vitro the altered function of mutated KCNJ5 channels has opened new horizons for the diagnosis and treatment of APA with KCNJ5 mutations in that it can allow identification and target treatment of PA patients harbouring a mutated APA. Thus, we aimed at investigating if clarithromycin and roxithromycin, two macrolides that potently blunt mutated Kir3.4 channel function in vitro, affect plasma aldosterone concentration in adrenal vein blood during AVS and in peripheral blood, respectively, in PA patients with a mutated APA. We designed two proof of concept studies. In study A: consecutive patients with an unambiguous biochemical evidence of PA will be exposed to a single dose of 250 mg clarithromycin during AVS, to assess its effect on the relative aldosterone secretion index in adrenal vein blood from the gland with and without APA. In study B: consecutive hypertensive patients submitted to the work-up for hypertension will receive a single oral dose of 150 mg roxithromycin. The experimental endpoints will be the change induced by roxithromycin of plasma aldosterone concentration and other steroids, direct active renin concentration, serum K + , systolic and diastolic blood pressure. We expect to prove that: (i) clarithromycin allows identification of mutated APA before adrenalectomy and sequencing of tumour DNA; (ii) the acute changes of plasma aldosterone concentration, direct active renin concentration, and blood pressure in peripheral venous blood after roxithromycin can be a proxy for the presence of an APA with somatic mutations.

  1. Pharmacological treatment of aldosterone excess

    NARCIS (Netherlands)

    Deinum, J.; Riksen, N.P.; Lenders, J.W.M.

    2015-01-01

    Primary aldosteronism, caused by autonomous secretion of aldosterone by the adrenals, is estimated to account for at least 5% of hypertension cases. Hypertension explains the considerable cardiovascular morbidity caused by aldosteronism only partly, calling for specific anti-aldosterone drugs. The

  2. Intracellular renin disrupts chemical communication between heart cells. Pathophysiological implications

    Directory of Open Access Journals (Sweden)

    Walmor eDe Mello

    2015-01-01

    Full Text Available The influence of intracellular renin on the process of chemical communication between cardiac cells was investigated in cell pairs isolated from the left ventricle of adult Wistar Kyoto rats. The enzyme together with Lucifer yellow CH was dialyzed into one cell of the pair using the whole cell clamp technique. The diffusion of the dye in the dialyzed and in non-dialyzed cell was followed by measuring the intensity of fluorescence in both cells as a function of time. The results indicated that; 1 under normal conditions, Lucifer Yellow flows from cell-to-cell through gap junctions; 2 the intracellular dialysis of renin (100nM disrupts chemical communication-an effect enhanced by simultaneous administration of angiotensinogen (100nM; 3 enalaprilat (10-9M administered to the cytosol together with renin reduced drastically the uncoupling action of the enzyme; 4 aliskiren (10-8M inhibited the effect of renin on chemical communication;5 the possible role of intracellular renin independently of angiotensin II (Ang II was evaluated including the increase of the inward calcium current elicited by the enzyme and the possible role of oxidative stress on the disruption of cell communication; 6 the possible harmful versus the beneficial effect of intracellular renin during myocardial infarction was discussed;7 the present results indicate that intracellular renin due to internalization or in situ synthesis, causes a severe impairment of chemical communication in the heart resulting in derangement of metabolic cooperation with serious consequences for heart function.

  3. 24-hour urinary aldosterone excretion test

    Science.gov (United States)

    Aldosterone - urine; Addison disease - urine aldosterone; Cirrhosis - serum aldosterone ... Laxative abuse Lower than normal levels may indicate Addison disease , a disorder in which the adrenal glands do ...

  4. Effects of Treating Primary Aldosteronism on Renal Function.

    Science.gov (United States)

    Kramers, Bart J; Kramers, Cornelis; Lenders, Jacques W M; Deinum, Jaap

    2017-03-01

    Longstanding primary aldosteronism (PA) has deleterious effects on renal function, often masked until treatment (adrenalectomy or spironolactone) is initiated. It has been suggested that PA causes relative glomerular hyperfiltration, explaining the decline in estimated glomerular filtration rate (eGFR) after treatment. In this retrospective study, the authors retrieved the clinical characteristics and eGFR of 134 PA patients before and 6 months after treatment. Using multiple regression analysis, the predictors for eGFR decline and the predictors of ultimately attained renal function in 113 patients was assessed. eGFR declined by 15.3±14.2 (range 19-63) mL/min, independent predictors were pretreatment plasma aldosterone, eGFR, plasma renin, and plasma potassium. Independent predictors of ultimately attained eGFR after treatment were pretreatment plasma aldosterone, age, eGFR, and plasma potassium. Our findings lend support to the hypothesis that higher aldosterone levels cause relative glomerular hyperfiltration. The severity of pretreatment aldosterone excess is the most important risk factor for renal function decline. ©2016 Wiley Periodicals, Inc.

  5. Bovine ovarian cells have (pro)renin receptors and prorenin induces resumption of meiosis in vitro.

    Science.gov (United States)

    Dau, Andressa Minussi Pereira; da Silva, Eduardo Pradebon; da Rosa, Paulo Roberto Antunes; Bastiani, Felipe Tusi; Gutierrez, Karina; Ilha, Gustavo Freitas; Comim, Fabio Vasconcellos; Gonçalves, Paulo Bayard Dias

    2016-07-01

    The discovery of a receptor that binds prorenin and renin in human endothelial and mesangial cells highlights the possible effect of renin-independent prorenin in the resumption of meiosis in oocytes that was postulated in the 1980s.This study aimed to identify the (pro)renin receptor in the ovary and to assess the effect of prorenin on meiotic resumption. The (pro)renin receptor protein was detected in bovine cumulus-oocyte complexes, theca cells, granulosa cells, and in the corpus luteum. Abundant (pro)renin receptor messenger ribonucleic acid (mRNA) was detected in the oocytes and cumulus cells, while prorenin mRNA was identified in the cumulus cells only. Prorenin at concentrations of 10(-10), 10(-9), and 10(-8)M incubated with oocytes co-cultured with follicular hemisections for 15h caused the resumption of oocyte meiosis. Aliskiren, which inhibits free renin and receptor-bound renin/prorenin, at concentrations of 10(-7), 10(-5), and 10(-3)M blocked this effect (Pmeiosis resumption, cumulus-oocyte complexes and follicular hemisections were treated with prorenin and with angiotensin II or saralasin (angiotensin II antagonist). Prorenin induced the resumption of meiosis independently of angiotensin II. Furthermore, cumulus-oocyte complexes cultured with forskolin (200μM) and treated with prorenin and aliskiren did not exhibit a prorenin-induced resumption of meiosis (Pmeiosis in cattle. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Czech Academy of Sciences Publication Activity Database

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

    2017-01-01

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

  7. Screening for primary aldosteronism using the newly developed IDS-iSYS® automated assay system

    Directory of Open Access Journals (Sweden)

    P.M. O’Shea

    2017-04-01

    Full Text Available Background: The recommended approach to screening for primary aldosteronism (PA in at-risk populations is to determine the ratio of aldosterone concentration (serum (SAC/plasma (PAC to renin measured in plasma as activity (PRA or concentration (DRC. However, lack of assay standardisation mandates the need for method-specific decision thresholds and clinical validation in the local population. Aim: The study objective was to establish method-specific aldosterone: renin ratio (ARR cut-offs for PA in men and women using the IDS-iSYS® assay system (IDS plc. Methods: A prospective cohort study design was used. PAC and DRC were measured immunochemically in ethylenediamine-tetraacetic acid (EDTA plasma on the IDS-iSYS® instrument. Results: A total of 437 subjects (218 men, 219 women were recruited including: healthy normotensive volunteers (n=266 and women taking the oral contraceptive pill (OCP; n=15; patients with essential hypertension (EH; n=128; confirmed PA (n=16; adrenal cortical carcinoma (ACC; n=3; Addison's disease (AD; n=4 and phaeochromocytoma/paraganglioma (PPGL; n=5. In this population, an ARR cut-off at >37.4 pmol/mIU provided 100% diagnostic sensitivity, 96% specificity and positive likelihood ratio for PA of 23:1. When the ARR decision threshold was stratified according to gender, a cut-off of >26.1 pmol/mIU in men and >113.6 pmol/mIU in women resulted in diagnostic sensitivity and specificity of 100%. Conclusion: This study demonstrates that decision thresholds for PA should not only be method-specific but also gender-specific. However, given the small number of PA patients (n=16, particularly women (n=4, further validation through a prospective study with a larger PA cohort is required before the thresholds presented here could be recommended for routine clinical use. Keywords: Primary aldosteronism, Renin, Aldosterone, Aldosterone: renin ratio (ARR, Sensitivity, Specificity

  8. The DD genotype of the angiotensin converting enzyme gene is negatively associated with right ventricular hypertrophy in male patients with chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    van Suylen, R. J.; Wouters, E. F.; Pennings, H. J.; Cheriex, E. C.; van Pol, P. E.; Ambergen, A. W.; Vermelis, A. M.; Daemen, M. J.

    1999-01-01

    The renin angiotensin system plays an important role in the development of pulmonary artery remodeling and right ventricular hypertrophy in hypoxia-induced pulmonary hypertension as may occur in patients with COPD. Several polymorphisms of genes encoding for components of the renin angiotensin

  9. Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

    Science.gov (United States)

    Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

    2008-01-01

    We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0·1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0·12 ± 0·03 and 0·15 ± 0·03 μg/h per liter, 126 ± 5 and 130 ± 5 ng/l respectively) (means ± s.e.m.). Despite stabilization of the circulating renin–angiotensin system, thyroid hormone induced cardiac hypertrophy (5·0 ± 0·5 vs 3·5 ± 0·1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74 ± 2 vs 48 ± 2%, 6·5 ± 0·8 vs 3·8 ± 0·4 ng/h per g, 231 ± 30 vs 149 ± 2 pg/g respectively). These results indicate that the local renin–angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy. PMID:9854175

  10. Alteration of hemorrhagic aldosterone response during sodium restriction, potassium supplement and diuresis

    International Nuclear Information System (INIS)

    Sung, H.K.; Ryu, Y.W.; Joo, B.S.; Koh, J.W.; Park, K.W.; Lee, J.K.

    1977-01-01

    Effect of sodium restriction with or without potassium supplement and furosemide diuresis on plasma aldosterone response to mild hemorrhage were studied in normotensive young volunteers. After an overnight fast, blood were drawn just before and 10, 20, 30, 50, 70, 90, and 120 minutes after the 3 H-aldosterone injection. The sum of blood delivered reached over 100ml (during two hours). Plasma aldosterone and renin were measured by means of radiommunoassay. The results were as followed: 1. Hemorrhage resulted in a moderate increase in plasma aldosterone level of volunteers with normal diet. 2. The mean figures of plasma aldosterone in subjects with sodium restriction and diuresis were likewise significantly increased by hemorrhage, however, the figure of the subjects with potassium supplement who already shown higher plasma level was without effect on hemorrhage. 3. Hemorrhage produced slight decrease in serum sodium concentration in every experimental conditions, although the changes were not significant. 4. Plasma renin activities after the hemorrhage followed a similar pattern with that of aldosterone, increased during sodium restriction or diuresis and unaffected during potassium supplement. (author)

  11. Alteration of Hemorrhagic Aldosterone Response During Sodium Restriction, Potassium Supplement and Diuresis

    International Nuclear Information System (INIS)

    Sung, Ho Kyung; Ryu, Yong Wun; Koh, Joo Whan; Park, Kee Won; Lee, Jang Kyu

    1977-01-01

    Effect of sodium restriction with or without potassium supplement and furosemide diuresis on plasma aldosterone response to mild hemorrhage were studied in normotensive young volunteers. After an overnight fast, blood were drawn just before and 10, 20, 30, 50, 70, 90, and 120 minutes after the 3H-aldosterone injection. The sum of blood delivered reached over 100 ml (during two hours). Plasma aldosterone and renin were measured by means of radioimmunoassay. The results were as followed; 1) Hemorrhage resulted in a moderate increase in plasma aldosterone level of volunteers with normal diet. 2) The mean figures of plasma aldosterone in subjects with sodium restriction and diuresis were likewise significantly increased by hemorrhage, however, the figure of the subjects with potassium supplement who already shown higher plasma level was without effect on hemorrhage. 3) Hemorrhage produced slight decrease in serum sodium concentration in every experimental conditions, although the changes were not significant. 4) Plasma renin activities after the hemorrhage followed a similar pattern with that of aldosterone, increased during sodium restriction or diuresis and unaffected during potassium supplement.

  12. Hyperpotassemia and bradycardia in a bedridden elderly woman with selective hypoaldosteronism associated with low renin activity.

    Science.gov (United States)

    Inada, Mitsuo; Iwasaki, Keiko; Imai, Chihiro; Hashimoto, Satoshi

    2010-01-01

    A bedridden 85-year-old woman had hyperpotassemia (7.7 mEq/L) and bradycardia (30/min). Endocrinologic findings revealed a decrease in the renin-aldosterone system and normal adrenoglucocorticoid function. The results were consistent with the abnormalities seen in selective hypoaldosteronism with low renin activity. In addition, 9 of 11 patients, selected randomly from 72 bedridden elderly patients with normal serum sodium and potassium levels in our hospital, had diminished plasma renin activity (PRA) and plasma aldosterone concentration (PAC). The present patient was prescribed nonsteroidal anti-inflammatory drug (NSAID). NSAID reduces renal potassium excretion through the inhibition of renal prostaglandin synthesis. Therefore, the use of NSAID in bedridden elderly patients might intensify the underlying asymptomatic hypoaldosteronism and cause life-threatening hyperpotassemia.

  13. Molecular and cellular mechanisms of aldosterone producing adenoma development

    Directory of Open Access Journals (Sweden)

    Sheerazed eBoulkroun

    2015-06-01

    Full Text Available Primary aldosteronism (PA is the most common form of secondary hypertension with an estimated prevalence of ~10% in referred patients. PA occurs as a result of a dysregulation of the normal mechanisms controlling adrenal aldosterone production. It is characterized by hypertension with low plasma renin and elevated aldosterone and often associated with hypokalemia. The two major causes of PA are unilateral aldosterone producing adenoma (APA and bilateral adrenal hyperplasia, accounting together for ~95% of cases. In addition to the well-characterized effect of excess mineralocorticoids on blood pressure, high levels of aldosterone also have cardiovascular, renal and metabolic consequences. Hence, long-term consequences of PA include increased risk of coronary artery disease, myocardial infarction, heart failure and atrial fibrillation. Despite recent progress in the management of patients with PA, critical issues related to diagnosis, subtype differentiation and treatment of non-surgically correctable forms still persist. A better understanding of the pathogenic mechanisms of the disease should lead to the identification of more reliable diagnostic and prognostic biomarkers for a more sensitive and specific screening and new therapeutic options. In this review we will summarize our current knowledge on the molecular and cellular mechanisms of APA development. On one hand, we will discuss how various animal models have improved our understanding of the pathophysiology of excess aldosterone production. On the other hand, we will summarize the major advances made during the last few years in the genetics of APA due to transcriptomic studies and whole exome sequencing. The identification of recurrent and somatic mutations in genes coding for ion channels (KCNJ5 and CACNA1D and ATPases (ATP1A1 and ATP2B3 allowed highlighting the central role of calcium signaling in autonomous aldosterone production by the adrenal.

  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.

    Science.gov (United States)

    Lely, A Titia; Heerspink, Hiddo J Lambers; Zuurman, Mike; Visser, Folkert W; Kocks, Menno J A; Boomsma, Frans; Navis, Gerjan

    2010-12-01

    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 effect of ACEi as well as the genotype-phenotype relationship, we hypothesize gene-environment interaction between sodium-status, the response to ACEi, and ACE genotype. Thirty-five male volunteers (26 ± 9 years; II n = 6, ID n = 18, DD n = 11) were studied during placebo and ACEi (double blind, enalapril 20 mg/day) on low [7 days 50 mmol Na/day (low salt)] and high [7 days 200 mmol Na/day (high salt)] sodium, with a washout of 6 weeks in-between. After each period mean arterial pressure (MAP) was measured before and during graded infusion of angiotensin II (Ang II). During high salt, ACEi reduced MAP in II and ID, but not in DD [II: 88 (78-94) versus 76 (72-88); ID: 87 (84-91) versus 83 (79-87); both P DD: 86 (82-96) versus 88 (80-90); ns, P DD: 84 (80-91) versus 81 (75-85); all P DD, with an 18% rise in MAP during the highest dose versus 22 and 31% in ID and II (P DD genotype during high salt, accompanied by blunted sensitivity to Ang II. Low salt corrects both abnormalities. Further analysis of this gene-environment interaction in patients may contribute to strategies for improvement of individual treatment efficacy.

  15. Impact of Angiotensin Type 1A Receptors in Principal Cells of the Collecting Duct on Blood Pressure and Hypertension.

    Science.gov (United States)

    Chen, Daian; Stegbauer, Johannes; Sparks, Matthew A; Kohan, Donald; Griffiths, Robert; Herrera, Marcela; Gurley, Susan B; Coffman, Thomas M

    2016-06-01

    The main actions of the renin-angiotensin system to control blood pressure (BP) are mediated by the angiotensin type 1 receptors (AT1Rs). The major murine AT1R isoform, AT1AR, is expressed throughout the nephron, including the collecting duct in both principal and intercalated cells. Principal cells play the major role in sodium and water reabsorption. Although aldosterone is considered to be the dominant regulator of sodium reabsorption by principal cells, recent studies suggest a role for direct actions of AT1R. To specifically examine the contributions of AT1AR in principal cells to BP regulation and the development of hypertension in vivo, we generated inbred 129/SvEv mice with deletion of AT1AR from principal cells (PCKO). At baseline, we found that BPs measured by radiotelemetry were similar between PCKOs and controls. During 1-week of low-salt diet (hypertension, there was a modest but significant attenuation of hypertension in PCKOs (163±6 mm Hg) compared with controls (178±2 mm Hg; Phypertension and epithelial sodium channel activation. © 2016 American Heart Association, Inc.

  16. Captopril suppression: limitations for confirmation of primary aldosteronism.

    Science.gov (United States)

    Westerdahl, Christina; Bergenfelz, Anders; Isaksson, Anders; Valdemarsson, Stig

    2011-09-01

    The aldosterone/renin ratio (ARR) is the first line screening test for primary aldosteronism (PA). However, in hypertensive patients with an increased ARR, PA needs to be confirmed by other means. A 25 mg oral captopril test was performed in 16 healthy subjects to obtain reference values for aldosterone and ARR at 120 minutes after the test. Subsequently these data were applied to 46 hypertensive patients screened for PA with an increased ARR. At 120 minutes after the captopril test ARR decreased in healthy subjects within a narrow range, but remained high in patients with PA and in patients with primary hypertension, especially for those with low renin characteristics. At 120 minutes after captopril, the range of ARR in primary hypertensive patients overlapped in 88% of the cases with the range of the ARR in the PA patients. Sensitivity and specificity of basal ARR and ARR after the captopril test to diagnose PA, calculated as receiver operator characteristics, showed an area under the curve of 0.595 for basal ARR and 0.664 for ARR at 120 minutes after the test. The ARR at 120 minutes after the captopril test is only marginally better than basal ARR in diagnosing PA in hypertensive patients screened with an increased ARR. Owing to an overall limited capacity to clearly discriminate PA from primary hypertension, the test could not therefore be recommended for the confirmatory diagnosis of PA.

  17. Primary aldosteronism. Clinical management

    International Nuclear Information System (INIS)

    Grant, C.S.; Carpenter, P.; van Heerden, J.A.; Hamberger, B.

    1984-01-01

    We retrospectively reviewed the clinical features, methods of diagnosis and localization, and results of treatment in 105 patients with primary aldosteronism seen between 1969 and 1981. Coincident with the use of computed tomography (CT), 131 I-6-beta-iodomethyl norcholesterol scans (NP-59), and postural response studies, the study group was temporally divided into pre-1976 and post-1976 groups, and subdivided into groups with aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia. Our results indicate that aldosterone postural response studies and CT differentiate and localize APA and IHA reliably. Adrenalectomy is a safe and effective treatment for APA, whereas medical treatment alone is preferable for IHA

  18. Blockade of chloride channels by DIDS stimulates renin release and inhibits contraction of afferent arterioles

    DEFF Research Database (Denmark)

    Jensen, B L; Skøtt, O

    1996-01-01

    or without ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and DIDS were not additive. In the absence of chloride, basal renin release was suppressed and the stimulatory effect of DIDS was abolished. The DIDS-induced enhancement of renin release was not dependent on bicarbonate....... Norepinephrine (5 x 10(-7)-1 x 10(-6) M) and angiotensin II (1 x 10(-8)-10(-6) M) evoked reversible and dose-dependent contractions of microperfused rabbit afferent arterioles. DIDS (0.5 mM) did not affect the basal diameter of the arterioles but strongly inhibited the response to angiotensin II and attenuated...

  19. Normotensive blood pressure in pregnancy: the role of salt and aldosterone.

    Science.gov (United States)

    Gennari-Moser, Carine; Escher, Geneviève; Kramer, Simea; Dick, Bernhard; Eisele, Nicole; Baumann, Marc; Raio, Luigi; Frey, Felix J; Surbek, Daniel; Mohaupt, Markus G

    2014-02-01

    A successful pregnancy requires an accommodating environment. Salt and water availability are critical for plasma volume expansion. Any changes in sodium intake would alter aldosterone, a hormone previously described beneficial in pregnancy. To date, it remains ambiguous whether high aldosterone or high salt intake is preferable. We hypothesized that increased aldosterone is a rescue mechanism and appropriate salt availability is equally effective in maintaining a normotensive blood pressure (BP) phenotype in pregnancy. We compared normotensive pregnant women (n=31) throughout pregnancy with young healthy female individuals (n=31-62) and performed salt sensitivity testing within the first trimester. Suppression of urinary tetrahydro-aldosterone levels by salt intake as measured by gas chromatography-mass spectrometry and urinary sodium excretion corrected for creatinine, respectively, was shifted toward a higher salt intake in pregnancy (Ppregnancy, neither high urinary tetrahydro-aldosterone nor sodium excretion was correlated with higher BP. In contrast, in nonpregnant women, systolic BP rose with aldosterone (Ppregnancy without causing aldosterone-induced hypertension. Second, salt seems to aid in BP lowering in pregnancy for reasons incompletely elucidated, yet involving renin suppression and potentially placental sensing mechanisms. Further research should identify susceptible individuals and clarify effector mechanisms.

  20. Aldosterone dysregulation with aging predicts renal vascular function and cardiovascular risk.

    Science.gov (United States)

    Brown, Jenifer M; Underwood, Patricia C; Ferri, Claudio; Hopkins, Paul N; Williams, Gordon H; Adler, Gail K; Vaidya, Anand

    2014-06-01

    Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal vascular and cardiovascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1124 visits) in the General Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression to stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess basal renal hemodynamics and the renal vascular responses to dietary sodium manipulation and angiotensin II infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β=-4.60; Page and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (Page may interact to mediate renal vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease.

  1. Update in diagnosis and management of primary aldosteronism.

    Science.gov (United States)

    Dick, Sofia M; Queiroz, Marina; Bernardi, Bárbara L; Dall'Agnol, Angélica; Brondani, Letícia A; Silveiro, Sandra P

    2018-02-23

    Primary aldosteronism (PA) is a group of disorders in which aldosterone is excessively produced. These disorders can lead to hypertension, hypokalemia, hypervolemia and metabolic alkalosis. The prevalence of PA ranges from 5% to 12% around the globe, and the most common causes are adrenal adenoma and adrenal hyperplasia. The importance of PA recognition arises from the fact that it can have a remarkably adverse cardiovascular and renal impact, which can even result in death. The aldosterone-to-renin ratio (ARR) is the election test for screening PA, and one of the confirmatory tests, such as oral sodium loading (OSL) or saline infusion test (SIT), is in general necessary to confirm the diagnosis. The distinction between adrenal hyperplasia (AH) or aldosterone-producing adenoma (APA) is essential to select the appropriate treatment. Therefore, in order to identify the subtype of PA, imaging exams such as computed tomography or magnetic ressonance imaging, and/or invasive investigation such as adrenal catheterization must be performed. According to the subtype of PA, optimal treatment - surgical for APA or pharmacological for AH, with drugs like spironolactone and amiloride - must be offered.

  2. Primary aldosteronism among newly diagnosed and untreated hypertensive patients in a Swedish primary care area.

    Science.gov (United States)

    Westerdahl, Christina; Bergenfelz, Anders; Isaksson, Anders; Nerbrand, Christina; Valdemarsson, Stig

    2011-03-01

    To evaluate the prevalence of primary aldosteronism (PA) in newly diagnosed and untreated hypertensive patients in primary care using the aldosterone/renin ratio (ARR), and to assess clinical and biochemical characteristics in patients with high and normal ARR. Patient survey study. A total of 200 consecutive patients with newly diagnosed and untreated hypertension from six primary health care centres in Sweden were included. ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was 65. Patients with an increased ARR were considered for confirmatory testing with the fludrocortisone suppression test (FST), followed by adrenal computed tomographic radiology (CT) and adrenal venous sampling (AVS). Of 200 patients, 36 patients had an ARR > 65. Of these 36 patients, 11 patients had an incomplete aldosterone inhibition during FST. Three patients were diagnosed with an aldosterone producing adenoma (APA) and eight with bilateral adrenal hyperplasia (BHA). Except for moderately lower level of P-K in patients with an ARR > 65 and in patients with PA, there were no biochemical or clinical differences found among hypertensive patients with PA compared with patients without PA. Eleven of 200 evaluated patients (5.5%) were considered to have PA. The diagnosis of PA should therefore be considered in newly diagnosed hypertensive subjects and screening for the diagnosis is warranted.

  3. Percutaneous computed tomography-guided ethanol injection in aldosterone-producing adrenocortical adenoma

    International Nuclear Information System (INIS)

    Rossi, R.; Savastano, S.; Tommaselli, A.P.

    1995-01-01

    The feasibility, safety and effectiveness of percutaneous computed tomography-guided ethanol injection (PEI-CT) was investigated in a patient affected by aldosterone-producing adenoma (APA). A 42-year-old male patient with typical features of hyperaldosteronism presented a solitary left adrenal adenoma measuring 2 cm, with a normal contralateral gland, evidenced by both CT scan and adrenal [ 75 Se-19]-nor-cholesterol scintigraphy. After normalization of potassium plasma levels, 4 ml of sterile 95% ethanol with 0.5 ml of 80% iothalamate sodium was injected. The procedure was completed in about 30 min. No severe pain or local complication was noted. Five hour after PEI, a fourfold and a twofold increase in aldosterone and cortisol plasma levels were observed, respectively. After 11 days on a normal sodium and potassium diet, normal potassium plasma levels and reduced aldosterone plasma levels were present, with reappearance of an aldosterone postural response. Plasma renin activity and aldosterone plasma levels normalized 1 month later, with reappearance also of a plasma renin activity postural response and maintenance of normal potassium plasma levels on a high sodium and normal potassium diet. The patient has remained hypertensive, although lower antihypertensive drug dosages have been employed. After 17 months, normal biochemical, hormonal and morphological findings were present. The authors suggested PEI-CT as a further alternative approach to surgery in the management of carefully selected patients with APA. 15 refs., 2 figs., 1 tab

  4. Case detection and diagnosis of primary aldosteronism – The consensus of Taiwan Society of Aldosteronism

    Directory of Open Access Journals (Sweden)

    Vin-Cent Wu

    2017-12-01

    Full Text Available Background/Purpose: Even though the increasing clinical recognition of primary aldosteronism (PA as a public health issue, its heightened risk profiles and the availability of targeted surgical/medical treatment being more understood, consensus in its diagnosis and management based on medical evidence, while recognizing the constraints of our real-world clinical practice in Taiwan, has not been reached. Methods: The Taiwan Society of Aldosteronism (TSA Task Force acknowledges the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics into the management of PA. Results: When there is suspicion of PA, a plasma aldosterone to renin ratio (ARR should be obtained initially. Patients with abnormal ARR will undergo confirmatory laboratory and image tests. Subtype classification with adrenal venous sampling (AVS or NP-59 nuclear imaging, if AVS not available, to lateralize PA is recommended when patients are considered for adrenalectomy. The strengths and weaknesses of the currently available identification methods are discussed, focusing especially on result interpretation. Conclusion: With this consensus we hope to raise more awareness of PA among medical professionals and hypertensive patients in Taiwan, and to facilitate reconciliation of better detection, identification and treatment of patients with PA. Index words: Primary aldosteronism, Guideline, TAIPAI, TSA

  5. Persistent Primary Aldosteronism Despite Iatrogenic Adrenal Hemorrhage After Adrenal Vein Sampling.

    Science.gov (United States)

    Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Abe, Ichiro; Kobayashi, Kunihisa; Ishii, Tatsu; Haraoka, Seiji; Urata, Hidenori

    2018-01-01

    Before surgery for primary aldosteronism (PA), localization is evaluated with adrenal vein sampling (AVS). A 56-year-old Japanese woman had a right adrenal mass, hypokalemia, and a high aldosterone/renin ratio. Stress tests confirmed the diagnosis of PA. Subsequently, preoperative AVS was performed and right adrenal hemorrhage (AH) occurred unexpectedly. Because hypertension persisted, laparoscopic right adrenalectomy was performed. Postoperatively, the blood pressure was normalized. Pathological examination revealed an adrenal cortical adenoma largely unaffected by necrosis and hemorrhage. Previous reports have also indicated that AH may not ameliorate PA. We discussed the clinical progress of AH and the measures to prevent causing AH.

  6. Persistent Primary Aldosteronism Despite Iatrogenic Adrenal Hemorrhage After Adrenal Vein Sampling

    Science.gov (United States)

    Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Abe, Ichiro; Kobayashi, Kunihisa; Ishii, Tatsu; Haraoka, Seiji; Urata, Hidenori

    2018-01-01

    Before surgery for primary aldosteronism (PA), localization is evaluated with adrenal vein sampling (AVS). A 56-year-old Japanese woman had a right adrenal mass, hypokalemia, and a high aldosterone/renin ratio. Stress tests confirmed the diagnosis of PA. Subsequently, preoperative AVS was performed and right adrenal hemorrhage (AH) occurred unexpectedly. Because hypertension persisted, laparoscopic right adrenalectomy was performed. Postoperatively, the blood pressure was normalized. Pathological examination revealed an adrenal cortical adenoma largely unaffected by necrosis and hemorrhage. Previous reports have also indicated that AH may not ameliorate PA. We discussed the clinical progress of AH and the measures to prevent causing AH. PMID:29238437

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

    Directory of Open Access Journals (Sweden)

    Yuan-Hua Xu

    2016-03-01

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

  8. A Novel Splice-Site Mutation in Angiotensin I-Converting Enzyme (ACE) Gene, c.3691+1G>A (IVS25+1G>A), Causes a Dramatic Increase in Circulating ACE through Deletion of the Transmembrane Anchor

    Science.gov (United States)

    Persu, Alexandre; Lambert, Michel; Deinum, Jaap; Cossu, Marta; de Visscher, Nathalie; Irenge, Leonid; Ambroise, Jerôme; Minon, Jean-Marc; Nesterovitch, Andrew B.; Churbanov, Alexander; Popova, Isolda A.; Danilov, Sergei M.; Danser, A. H. Jan; Gala, Jean-Luc

    2013-01-01

    Background Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. Methods and Results Two Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or cardiovascular disease. The levels of renin-angiotensin-aldosterone system components in the mutated cases and wild-type controls were similar, both at baseline and after 50 mg captopril. Compared with non-affected members, quantification of ACE surface expression and shedding using flow cytometry assay of dendritic cells derived from peripheral blood monocytes of affected members, demonstrated a 50% decrease and 3-fold increase, respectively. Together with a dramatic increase in circulating ACE levels, these findings argue in favor of deletion of transmembrane anchor, leading to direct secretion of ACE out of cells. Conclusions We describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences. PMID:23560051

  9. Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction).

    Science.gov (United States)

    Schroten, Nicolas F; Damman, Kevin; Hemmelder, Marc H; Voors, Adriaan A; Navis, Gerjan; Gaillard, Carlo A J M; van Veldhuisen, Dirk J; Van Gilst, Wiek H; Hillege, Hans L

    2015-05-01

    We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality. Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals. Patients with left ventricular ejection fraction ≤45% and estimated GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at baseline and 26 weeks. After 41 patients were included, the trial was halted based on an interim safety analysis showing futility. Mean age was 68 ± 9 years, 82% male, GFR (49 ± 16 mL/min per 1.73 m(2)), RBF (294 ± 77 mL/min per 1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 ± 30 vs +14 ± 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased significantly in the aliskiren group compared with placebo (-2.8 ± 6.0 vs +4.4 ± 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 ± 3.3 vs +1.1 ± 3.1%; P = .01). There were no significant differences in plasma aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase (P = .007). Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction. Copyright © 2015 Mosby, Inc. All rights reserved.

  10. Genomic and nongenomic effects of aldosterone in the rat heart: why is spironolactone cardioprotective?

    NARCIS (Netherlands)

    W. Chai (Wenxia); I.M. Garrelds (Ingrid); U. Arulmani (Udayasankar); R.G. Schoemaker (Regien); J.M.J. Lamers (Jos); A.H.J. Danser (Jan)

    2005-01-01

    textabstract1. Mineralocorticoid receptor (MR) antagonism with spironolactone reduces mortality in heart failure on top of ACE inhibition. To investigate the underlying mechanism, we compared the actions of both aldosterone and spironolactone to those of angiotensin (Ang) II in the rat heart. 2.

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

    DEFF Research Database (Denmark)

    Tarnow, L; Kjeld, T; Knudsen, E

    2000-01-01

    AIMS/HYPOTHESIS: Reports on a putative synergism between poor glycaemic control and carriage of the angiotensin II type 1 receptor (AGTR1) C1166-allele and risk of diabetic nephropathy have been conflicting. Therefore, we investigated the interaction between long-term glycaemic control and three...... studied Caucasian patients with Type I (insulin-dependent) diabetes mellitus and nephropathy (120 men 74 women, age 41.1 +/- 9.6 years, diabetes duration 28 +/- 8 years) and long-standing Type I diabetic patients with persistent normoalbuminuria (112 men 69 women, age 42.5 +/- 10.0 years, diabetes...... duration 27 +/- 9 years). Genotyping was PCR-based and metabolic control estimated from all measurements of HbA1c done in each patient [average (range) n = 31 (6-74)]. The median observation time (range) was 13.5 (2-14) years. RESULTS: Type I diabetic patients with a history of poor glycaemic control (HbA1...

  12. Evidence for Heterodimerization and Functional Interaction of the Angiotensin Type 2 Receptor and the Receptor MAS

    DEFF Research Database (Denmark)

    Leonhardt, Julia; Villela, Daniel C.; Teichmann, Anke

    2017-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor MAS are receptors of the protective arm of the renin-angiotensin system. They mediate strikingly similar actions. Moreover, in various studies, AT2R antagonists blocked the effects of MAS agonists and vice versa. Such cross-inhibition may in...

  13. Angiotensin II promotes development of the renal microcirculation through AT1 receptors

    DEFF Research Database (Denmark)

    Madsen, Kirsten; Marcussen, Niels; Pedersen, Michael

    2010-01-01

    Pharmacologic or genetic deletion of components of the renin-angiotensin system leads to postnatal kidney injury, but the roles of these components in kidney development are unknown. To test the hypothesis that angiotensin II supports angiogenesis during postnatal kidney development, we quantifie...

  14. The angiotensin II type 1 receptor antagonist Losartan binds and activates bradykinin B2 receptor signaling

    DEFF Research Database (Denmark)

    Bonde, Marie Mi; Olsen, Kristine Boisen; Erikstrup, Niels

    2011-01-01

    The angiotensin II type 1 receptor (AT1R) blocker (ARB) Losartan has cardioprotective effects during ischemia-reperfusion injury and inhibits reperfusion arrhythmias -effects that go beyond the benefits of lowering blood pressure. The renin-angiotensin and kallikrein-kinin systems are intricately...

  15. Estrogen effects on angiotensin receptors are modulated by pituitary in female rats

    International Nuclear Information System (INIS)

    Douglas, J.G.

    1987-01-01

    The present studies were designed to test the hypothesis that changes in angiotensin II (ANG II) receptors might modulate the layered target tissue responsiveness accompanying estradiol administration. Estradiol was infused continuously in oophorectomized female rats. Aldosterone was also infused in control and experimental animals to avoid estrogen-induced changes in renin and ANG II. ANG II binding constants were determined in radioreceptor assays. Estradiol increased binding site concentration in adrenal glomerulosa by 76% and decreased binding sites of uterine myometrium and glomeruli by 45 and 24%, respectively. There was an accompanying increase in the affinity of ANG II binding to adrenal glomerulosa and uterine myometrium. Because estrogen is a potent stimulus of prolactin release from the pituitary of rodents, studies were also designed to test the hypothesis that prolactin may mediate some or all of the estrogen-induced effects observed. Hypophysectomy abolished estradiol stimulation of prolactin release and most ANG II receptor changes. Prolactin administration to pituitary intact rats was associated with a 50% increase in receptor density of adrenal glomerulosa simulating estradiol administration. However, the changes in glomeruli and uterine myometrium were opposite in that both tissues also increased receptor density, suggesting that prolactin was not the sole mediator of the estrogen-induced receptor changes. In conclusion, regulation of ANG II receptors in a number of diverse target tissues by estradiol is complex with contributions from estrogens and pituitary factors, which include but do not exclusively involve prolactin

  16. Impact of angiotensin-converting enzyme gene polymorphism on neurohormonal responses to high- versus low-dose enalapril in advanced heart failure.

    Science.gov (United States)

    Tang, W H Wilson; Vagelos, Randall H; Yee, Yin-Gail; Fowler, Michael B

    2004-11-01

    The impact of angiotensin-converting enzyme (ACE) gene polymorphism on neurohormonal dose response to ACE inhibitor therapy is unclear. ACE Insertion (I) or Deletion (D) genotype was determined in 74 patients with chronic heart failure who were randomly assigned to receive either high-dose or low-dose enalapril over a period of 6 months. Monthly pre-enalapril and post-enalapril neurohormone levels (serum ACE activity (sACE), plasma angiotensin II (A-II), plasma renin activity (PRA), and serum aldosterone (ALDO) were compared between genotype subgroups and between patients who received high- or low-dose enalapril within each genotype subgroup. At baseline, predose/postdose sACE and postdose PRA were significantly higher in the DD genotype. At 6-month follow-up, postdose sACE was reduced in a dose-dependent fashion in all three genotypes (P sACE were consistently higher in the DD genotype when compared with ID or II subgroups. Despite a dose-dependent suppression of sACE, there were no observed statistically significant differences in ALDO and A-II suppression or escape with escalating doses of enalapril within each subgroup.

  17. Organisation and functional role of the brain angiotensin system

    OpenAIRE

    Catherine Llorens-Cortes; Frederic AO Mendelsohn

    2002-01-01

    The discovery that all components of the renin-angiotensin system (RAS) are present in the brain led investigators to postulate the existence of a local brain RAS. Supporting this, angiotensin immunoreactive neurones have been visualised in the brain. Two major pathways were described: a forebrain pathway which connects circumventricular organs to the median preoptic nucleus, paraventricular and supraoptic nuclei, and a second pathway connecting the hypothalamus to the medulla oblongata. Bloo...

  18. Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression

    DEFF Research Database (Denmark)

    Dhamrait, Sukhbir S.; Maubaret, Cecilia; Pedersen-Bjergaard, Ulrik

    2016-01-01

    Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial...... amongst UCP3-55C (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P 

  19. Re-evaluation of the fludrocortisone test: duration, NaCl supplementation and cut-off limits for aldosterone.

    Science.gov (United States)

    Westerdahl, Christina; Bergenfelz, Anders; Larsson, Johanna; Nerbrand, Christina; Valdemarsson, Stig; Wihl, Anders; Isaksson, Anders

    2009-01-01

    Primary aldosteronism (PA) is the most common form of secondary hypertension. Thus, the aims of this study were: (1) to clarify whether the fludrocortisone suppression test (FST), which confirms autonomous aldosterone secretion, is reliable when carried out during a shorter period of time and (2) to confirm the importance of NaCl supplementation. The cut-off limits already obtained for aldosterone in healthy subjects during the FST were applied in hypertensive patients with a high aldosterone to renin ratio (ARR). The healthy subjects were allocated to three groups. Fludrocortisone was administered 4 times daily over 4 days and sodium chloride was supplemented in 3 different doses. The result was applied in 24 hypertensive patients, in 24 healthy subjects (10 women (23-38 years old) and 14 men (23-58 years old)) and in 24 patients with hypertension and high ARR (16 women (45-74 years old) and 8 men (56-73 years old)). Blood pressure, aldosterone, renin, potassium and sodium were measured. After three days of FST, there was a significant decrease in the serum level of aldosterone in the healthy subjects, regardless of high or low sodium chloride supplementation (p<0.001). The decrease in serum aldosterone was significantly less pronounced in patients with PA than in healthy subjects and hypertensive patients without PA (p<0.001). The 95th percentile of plasma aldosterone at the end of the test was 225 pmol/L. The FST can be shortened to 3 days and a daily 500 mg NaCl supplementation is sufficient. A cut-off value for aldosterone of 225 pmol/L after 4 days with FST is appropriate.

  20. Decreased plasma prorenin levels in primary aldosteronism: potential diagnostic implications.

    Science.gov (United States)

    Berge, Constance; Courand, Pierre-Yves; Harbaoui, Brahim; Paget, Vinciane; Khettab, Fouad; Bricca, Giampiero; Fauvel, Jean-Pierre; Lantelme, Pierre

    2015-01-01

    Primary aldosteronism could exert a negative feedback on prorenin secretion, of possibly different magnitude, whether it is related to an aldosterone-producing adenoma (APA) or an idiopathic hyperaldosteronism (IHA). The objectives of this study were to evaluate the level of prorenin in three subgroups: APA, IHA, and essential hypertension; and the performance of the aldosterone-to-prorenin ratio (APR) for the diagnosis of an APA. Seven hundred and forty-six hypertensive patients with a standardized work-up, including a prorenin measurement, were considered. Ninety-six patients without neutral treatment and 38 patients with other forms of secondary hypertension were excluded. APA and IHA were categorized according to computed tomography scan, adrenal venous sampling, pathological analysis and improvement of hypertension after surgery. Thirty-five patients had a diagnosis of APA, 57 of IHA and 504 of essential hypertension. Prorenin was lower in APA and IHA than in essential hypertension (32.9, 40.4 and 50.3  pg/ml, respectively; P < 0.001). APR was higher in patients with APA and IHA than in those with essential hypertension (24.0, 11.8, and 4.0  pmol/l per pg/ml, respectively; P < 0.001). The APR was more discriminant than the aldosterone-to-renin ratio to identify APA compared to IHA (area under the receiver operating curve at 0.750 and 0.639, respectively; P = 0.04). The optimal cut-off values were 22  pmol/l per pg/ml for APR (sensitivity 57.0%, specificity 93.0%) and 440  pmol/l per pg/ml for aldosterone-to-renin ratio (sensitivity 54.3%, specificity 82.5%). Primary aldosteronism and particularly its most caricatural form, that is APA, seems associated with a lower level of prorenin than essential hypertension. The APR could be included in the diagnostic strategy of APA.

  1. Relationship between aldosterone and the metabolic syndrome in patients with obstructive sleep apnea hypopnea syndrome: effect of continuous positive airway pressure treatment.

    Directory of Open Access Journals (Sweden)

    Antonia Barceló

    Full Text Available BACKGROUND: Metabolic syndrome (MS occurs frequently in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS. We hypothesized that aldosterone levels are elevated in OSAHS and associated with the presence of MS. METHODS: We studied 66 patients with OSAHS (33 with MS and 33 without MS and 35 controls. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III clinical criteria. Measurements of plasma renin activity (PRA, aldosterone, aldosterone:PRA ratio, creatinine, glucose, triglycerides, cholesterol and HDL cholesterol were obtained at baseline and after CPAP treatment. RESULTS: Aldosterone levels were associated with the severity of OSAHS and higher than controls (p = 0.046. Significant differences in aldosterone levels were detected between OSAHS patients with and without MS (p = 0.041. A significant reduction was observed in the aldosterone levels in patients under CPAP treatment (p = 0.012. CONCLUSION: This study shows that aldosterone levels are elevated in OSAHS in comparison to controls, and that CPAP therapy reduces aldosterone levels. It also shows that aldosterone levels are associated with the presence of metabolic syndrome, suggesting that aldosterone excess might predispose or aggravate the metabolic and cardiovascular complications of OSAHS. TRIAL REGISTRATION: The study is not a randomized controlled trial and was not registered.

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

    Czech Academy of Sciences Publication Activity Database

    Kurtz, T. W.; Pravenec, Michal

    2008-01-01

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

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

    Science.gov (United States)

    Tagawa, Miho; Ogata, Ai; Hamano, Takayuki

    2015-01-01

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

  4. Improved interpretation of renal-vein-renin-ratio by simultaneous determination of renal 131I-hippuric-acid-clearance-ratio in patients with renovascular hypertension

    International Nuclear Information System (INIS)

    Helber, A.; Boenner, G.; Hummerich, W.; Wambach, G.; Meurer, K.A.; Dvorak, K.; Lent, V.; Zehle, A.; Kaufmann, W.; Koeln Univ.; Staedtisches Krankenhaus Koeln-Merheim; Staedtisches Krankenhaus Koeln-Merheim; Koeln Univ.

    1979-01-01

    In patients with unilateral vascular kidney disease and hypertension, ratio of renal-vein-renin was compared with 131 I-Hippuric-acid clearance and change in blood pressure during Saralasininfusion. The ratio of renal-vein-renin was positively correlated with the ratio in renal plasma flow between the kidneys in all patients studied. The ratio of renins therefore is a result of two factors: The difference in renin secretion and the difference in blood flow in the two kidneys. In patients with angiotensin independent hypertension renin-ratios up to 2.0 were found without relevance to elevated blood pressure. When the difference in renal blood flow between both kidneys was small, even a slight difference in renal vein renin indicated hypertension related to increased renin secretion. (orig./AJ) [de

  5. Angiotensin antagonists in the dog with chronic pericardial tamponade

    International Nuclear Information System (INIS)

    Moore, G.J.; Taub, K.J.

    1980-01-01

    Assessing the role played by angiotensin in the pathogenesis and maintenance of the renal function and perfusion abnormalities dogs with chronic pericardial tamponade were used in the experiment as a stable model of chronic low output heart failure. The heptapeptide and octapeptide antagonist were used. The results of the experiments suggest that there is a role for angiotensin in the pathologenesis of congestive heart failure. The renin-angiotensin system was activated in the model. Plasma renin activity was elevated and increased further in response to angiotensin blockade. Under the experiment condition there was no evidence for a role for angiotensin in the maintenance of arterial blood pressure. But there was angiotensin-mediated renal vasoconstriction and a reduction in renal blood flow. Both analogues of angiotensin were able to antagonize this effect in similar fashion. Failure to achieve a natriuresis in response to angiotensin blockade may reflect the redistribution of blood flow that occured and suggests that additional factors are operative in this model. (APR)

  6. Estimation of urinary angiotensin II by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Fukuchi, S [Tohoku Univ., Sendai (Japan). School of Medicine

    1974-11-01

    Urine samples were collected from fasting subjects after maintaining posture for 2 hr in early morning. Urinary angiotensin II was extracted with SE-Sephadex. The extracts, after being dissolved in phosphate buffer, pH 7.5, were measured by radioimmunoassay. Recovery, sensitivity and accuracy were found to be satisfactory. The normal values obtained from 6 subjects were 52-280 pg/2 hr. The values were almost normal in essential hypertension and in chronic glomerulonephritis. They were high in 3 out of 6 cases with renovascular hypertension and subsequently dropped after surgery. In 6 cases with primary aldosteronism, very low levels were found. These increased after the removal of adrenal adenomas. No positive correlation between simultaneous plasma and urinary angiotensin samples was apparent. Also no positive correlation between urinary angiotensin and urine volume was found. In renovascular hypertention, during glucose infusion, lower values in urine volume and angiotensin excretion were observed on the stenotic side as compared to the intact side. Thus, the angiotensin excretion rate does not appear to be regulated by arterial angiotensin concentration, but rather by the angiotensin perfusion rate.

  7. Localization of primary aldosteronism

    International Nuclear Information System (INIS)

    Pagny, J.Y.; Chatellier, G.; Raynaud, A.; Plouin, P.F.; Corvol, P.

    1988-01-01

    After diagnosis of primary aldosteronism on the basis of biochemical evidence, the detection of the tumour is of crucial importance in the management of the disease. The efficacy of CT-Scan, Iodo-Cholesterol Scintigraphy, digitalized phlebography, adrenal vein sampling for steroid measurements (AVS), and Nuclear Magnetic Resonance (NMR) in 160 hypertensive patients with primary aldosteronism was reviewed. Diagnosis of Conn's adenoma (n=96) or Adrenal Hyperplasia (n=40) was confirmed by surgery or at least two concordant tumour localization tests. Scintigraphy gave a correct diagnosis in 53% of the 51 exams, CT-Scan in 82% of the 85 exams, and phlebography in 79% of 61 exams. Plasma Aldosterone/ Cortisol ratio was 5 times higher on the side of adenoma in 55% of the 47 cases but this ratio was also present in 23% of 22 patients with adrenal hyperplasia. Each procedure exhibited few false positive and false negative cases. NMR performed in 15 patients with Conn's adenoma identified all the cases. But tumours displayed a signal close to the liver signal and identical to the normal adrenal. These results and the risk of invasive procedure (failure of catheterization of the right adrenal vein (n=6) and adrenal haematoma (n=2) lead to propose a schema of exploration of patients with primary aldosteronism. The CT-Scan could be performed at the first step once the biological diagnosis confirmed. Phlebography and AVS will be performed only if tumour was less than 1 cm at the CT-Scan despite important biological abnormalities. This schema requires to be validated by a prospective evaluation [fr

  8. Screening for primary aldosteronism in an argentinian population: a multicenter prospective study.

    Science.gov (United States)

    Leal Reyna, Mariela; Gómez, Reynaldo M; Lupi, Susana N; Belli, Susana H; Fenili, Cecilia A; Martínez, Marcela S; Ruibal, Gabriela F; Rossi, María A; Chervin, Raúl A; Cornaló, Dora; Contreras, Liliana N; Costa, Liliana; Nofal, María T; Damilano, Sergio A; Pardes, Ester M

    2015-10-01

    Primary aldosteronism (PA) is characterized by the autonomous overproduction of aldosterone. Its prevalence has increased since the use of the aldosterone (ALD)/plasma renin activity (PRA) ratio (ARR). The objective of this study is to determine ARR and ARC (ALD/plasma renin concentration ratio) cut-off values (COV) and their diagnostic concordance (DC%) in the screening for PA in an Argentinian population.Design multicenter prospective study. We studied 353 subjects (104 controls and 249 hypertensive patients). Serum aldosterone, PRA and ARR were determined. In 220 randomly selected subjects, 160 hypertensive patients and 60 controls, plasma renin concentration (PRC) was simultaneously measured and ARC was determined. According to the 95th percentile of controls, we determined a COV of 36 for ARR and 2.39 for ARC, with ALD ≥ 15 ng/dL. In 31/249 hypertensive patients, ARR was ≥ 36. PA diagnosis was established in 8/31 patients (23/31 patients did not complete confirmatory tests). DC% between ARR and ARC was calculated. A significant correlation between ARR and ARC (r = 0.742; p 0.3 ng/mL/h and PRC > 5 pg/mL. DC% for ARR and ARC above or below 36 and 2.39 was 79.1%, respectively. This first Argentinian multicenter study determined a COV of 36 for ARR and 2.39 for ARC. Applying an ARR ≥ 36 in the hypertensive group, we confirmed PA in a higher percentage of patients than the previously reported one in our population. As for ARC, further studies are needed for its clinical application, since DC% is acceptable only for medium range renin values.

  9. Estimation of the number of angiotensin II AT1 receptors in rat kidney afferent and efferent arterioles

    DEFF Research Database (Denmark)

    Razga, Zsolt; Nyengaard, Jens Randel

    2007-01-01

    of angiotensin II AT1 receptors along the length of the arterioles and per arteriole, we combined immunoelectron microscopy with stereology. RESULTS: The number of AT1 receptor molecules was significantly lower in the renin-positive smooth muscle cells (SMCs) than in the renin-negative SMCs of the afferent...

  10. Blockade of AT1 receptors by losartan did not affect renin gene expression in kidney medulla

    Czech Academy of Sciences Publication Activity Database

    Tybitanclová, K.; Szabová, L.; Grima, M.; Ingert, C.; Železná, Blanka; Zórad, Š.

    2006-01-01

    Roč. 25, č. 1 (2006), s. 43-51 ISSN 0231-5882 Grant - others:VEGA(SK) 2/5090/25 Institutional research plan: CEZ:AV0Z50520514 Keywords : AT1 receptor * renin-angiotensin system * kidneys Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.771, year: 2006

  11. Impact of glycaemic control on the effect of direct renin inhibition in the AVOID study

    DEFF Research Database (Denmark)

    Persson, Frederik; Lewis, Julia B; Lewis, Edmund J

    2012-01-01

    Hyperglycaemia induces development and progression of microvascular complications in diabetes. A direct link between high glucose levels and intrarenal renin-angiotensin activation has been demonstrated. This post-hoc analysis assessed the influence of baseline glycaemic control on the reduction ...

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

    Directory of Open Access Journals (Sweden)

    Hernán Trimarchi

    2007-10-01

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

  13. [Role of adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes].

    Science.gov (United States)

    Li, H Y; Li, P; Shen, S M; Zhang, X B; Feng, W H; Huang, H; Chen, W; Zhu, D L

    2017-11-14

    Objective: To investigate the role of adrenal vein sampling (AVS) in identifying the subtype of primary aldosteronism (PA). Methods: AVS was performed in 50 patients who were confirmed as PA between September 2010 and September 2016 in Nanjing Drum Tower Hospital. Clinical, biochemical and follow-up data were reviewed retrospectively. Bilaterally simultaneous catheterization without cosyntropin stimulation and contemporaneous cortisol measurement during AVS were used. Selectivity index (SI)≥1.5 suggested that the sample was from the adrenal vein.Lateralization index (LI) ≥2 suggested unilateral disease.Clinical data was further compared and the AVS findings were analyzed. Results: AVS was successful performed in 41 cases of 50 patients, and the success rate was 82%. According to the results of AVS and postoperative pathology, 41 cases were divided into aldosterone-producing adenoma (APA)/unilateral adrenal hyperplasia (UAH) group (24 cases) and idiopathic hyperaldosteronism (IHA) group (17 cases). Compared with IHA group, patients with APA/UAH showed longer duration of hypertension[10.0 (5.0, 13.0) y vs 4.0 (2.0, 8.0) y, P =0.046], higher proportion of hypokalemia (95.8% vs 64.7%, P =0.009). Furthermore, patients with APA/UAH demonstrated lower plasma renin activity ( P =0.089), higher plasma aldosterone concentration and aldosterone to renin ratio (ARR) (both P AVS. AVS is useful in subtype diagnosis of PA with equivocal imaging findings.

  14. Angiotensin II type 1 receptor (A1166C) gene polymorphism in ...

    African Journals Online (AJOL)

    H. El-banawy

    2015-01-05

    Jan 5, 2015 ... sure and body fluids, via renin-angiotensin–aldosterone system ... the most studied one is the A1166C variant.2–5,8,10–14 It is a ... polymorphism on the development of ESRD in adult Egyptian ... teaching hospital, Alexandria University. ..... important part of the clinical process of renal risk identifica- tion.

  15. Association of Post-Saline Load Plasma Aldosterone Levels With Left Ventricular Hypertrophy in Primary Hypertension.

    Science.gov (United States)

    Catena, Cristiana; Verheyen, Nicolas D; Url-Michitsch, Marion; Kraigher-Krainer, Elisabeth; Colussi, GianLuca; Pilz, Stefan; Tomaschitz, Andreas; Pieske, Burkert; Sechi, Leonardo A

    2016-03-01

    Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity in hypertension. Current evidence suggests a contribution to LVH of plasma aldosterone levels that are inappropriately elevated for the salt status. The aim of this study was to investigate whether inappropriate modulation of aldosterone production by a saline load is associated with left ventricular (LV) mass in hypertensive patients. In 90 hypertensive patients free of clinically relevant cardiovascular complications in whom secondary forms of hypertension were ruled out, we performed a standard intravenous saline load (0.9% NaCl, 2 l in 4 hours) with measurement of plasma aldosterone and active renin at baseline and end of infusion. Bi-dimensional echocardiography was performed for the assessment of cardiac morphology and function. LVH was present in 19% of patients who had significantly worse renal function and higher body mass, blood pressure, and plasma aldosterone levels measured both at baseline and after the saline load than patients without LVH. LV mass was directly related to age, body mass, systolic blood pressure, duration of hypertension, baseline, and post-saline load plasma aldosterone levels and inversely to glomerular filtration. Multivariate regression analysis showed independent correlation of LV mass with body mass, systolic blood pressure, and plasma aldosterone levels measured after intravenous saline load, but not at baseline. In patients with hypertension, aldosterone levels measured after intravenous saline load are related to LV mass independent of age, body mass, and blood pressure, suggesting that limited ability of salt to modulate aldosterone production could contribute to LVH. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Pharmacological significance of the interplay between angiotensin receptors: MAS receptors as putative final mediators of the effects elicited by angiotensin AT1 receptors antagonists.

    Science.gov (United States)

    Pernomian, Larissa; Pernomian, Laena; Gomes, Mayara S; da Silva, Carlos H T P

    2015-12-15

    The interplay between angiotensin AT1 receptors and MAS receptors relies on several inward regulatory mechanisms from renin-angiotensin system (RAS) including the functional crosstalk between angiotensin II and angiotensin-(1-7), the competitive AT1 antagonism exhibited by angiotensin-(1-7), the antagonist feature assigned to AT1/MAS heterodimerization on AT1 signaling and the AT1-mediated downregulation of angiotensin-converting enzyme 2 (ACE2). Recently, such interplay has acquired an important significance to RAS Pharmacology since a few studies have supporting strong evidences that MAS receptors mediate the effects elicited by AT1 antagonists. The present Perspective provides an overview of the regulatory mechanisms involving AT1 and MAS receptors, their significance to RAS Pharmacology and the future directions on the interplay between angiotensin receptors. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Angiotensin II dependent cardiac remodeling in the eel Anguilla anguilla involves the NOS/NO system

    DEFF Research Database (Denmark)

    Filice, Mariacristina; Amelio, Daniela; Garofalo, Filippo

    2017-01-01

    Angiotensin II (AngII), the principal effector of the Renin-Angiotensin System (RAS), plays an important role in controlling mammalian cardiac morpho-functional remodelling. In the eel Anguilla anguilla, one month administration of AngII improves cardiac performance and influences the expression ...

  18. Renoprotective effects of angiotensin II receptor blockade in type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Andersen, S; Tarnow, L; Rossing, P

    2000-01-01

    BACKGROUND: Angiotensin I-converting enzyme (ACE) inhibitors reduce angiotensin II formation and induce bradykinin accumulation. Animal studies suggest that bradykinin may play a role for the effects of ACE inhibition on blood pressure and kidney function. Therefore, we compared the renal and hem...... inhibition is primarily caused by interference in the renin-angiotensin system. Our study suggest that losartan represents a valuable new drug in the treatment of hypertension and proteinuria in type 1 diabetic patients with diabetic nephropathy....... and hemodynamic effects of specific intervention in the renin-angiotensin system by blockade of the angiotensin II subtype-1 receptor to the effect of ACE inhibition. METHODS: A randomized, double-blind, cross-over trial was performed in 16 type 1 diabetic patients (10 men), age 42 +/- 2 years (mean +/- SEM...

  19. Angiotensin II receptor one (AT1) mediates dextrose induced endoplasmic reticulum stress and superoxide production in human coronary artery endothelial cells.

    Science.gov (United States)

    Haas, Michael J; Onstead-Haas, Luisa; Lee, Tracey; Torfah, Maisoon; Mooradian, Arshag D

    2016-10-01

    Renin-angiotensin-aldosterone system (RAAS) has been implicated in diabetes-related vascular complications partly through oxidative stress. To determine the role of angiotensin II receptor subtype one (AT1) in dextrose induced endoplasmic reticulum (ER) stress, another cellular stress implicated in vascular disease. Human coronary artery endothelial cells with or without AT1 receptor knock down were treated with 27.5mM dextrose for 24h in the presence of various pharmacologic blockers of RAAS and ER stress and superoxide (SO) production were measured. Transfection of cells with AT1 antisense RNA knocked down cellular AT1 by approximately 80%. The ER stress was measured using the placental alkaline phosphatase (ES-TRAP) assay and western blot analysis of glucose regulated protein 78 (GRP78), c-jun-N-terminal kinase 1 (JNK1), phospho-JNK1, eukaryotic translation initiation factor 2α (eIF2α) and phospho-eIF2α measurements. Superoxide (SO) generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride (MCLA) chemiluminescence. In cells with AT1 knock down, dextrose induced ER stress was significantly blunted and treatment with 27.5mM dextrose resulted in significantly smaller increase in SO production compared to 27.5mM dextrose treated and sham transfected cells. Dextrose induced ER stress was reduced with pharmacologic blockers of AT1 (losartan and candesartan) and mineralocorticoid receptor blocker (spironolactone) but not with angiotensin converting enzyme inhibitors (captopril and lisinopril). The dextrose induced SO generation was inhibited by all pharmacologic blockers of RAAS tested. The results indicate that dextrose induced ER stress and SO production in endothelial cells are mediated at least partly through AT1 receptor activation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD).

    Science.gov (United States)

    Ramanathan, Gnanasambandan; Ghosh, Santu; Elumalai, Ramprasad; Periyasamy, Soundararajan; Lakkakula, Bhaskar V K S

    2016-06-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. m0 ethods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction. All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD. The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients.

  1. Plasma renin activity in patients with ischaemic heart disease

    International Nuclear Information System (INIS)

    Urbanek, J.; Hofman, O.; Reisenauer, R.; Slaby, A.

    1977-01-01

    Plasma renin activity (PRA) stimulated by upright posture was measured in 300 men aged 45-64 years using a radioimmunoassay of angiotensin-I. The examined subjects were normotensive or patients with benign essential hypertension and were divided into 6 groups according to the absence of manifest atherosclerosis, the presence of definite angina pectoris or a history of myocardial infarction. Each group contained 50 unselected subjects, with a comparable mean age. Significant differences in mean PRA were found between corresponding groups of hypertensives and normotensives, the values in hypertensives being lower. The percentage of low renin values was higher in hypertensives with ischaemic heart disease than in other groups. It is suggested that this finding might be explained by functional disturbances in the kidneys in hypertensives with ischaemic heart disease. (orig.) [de

  2. Plasma renin activity in patients with ischaemic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Urbanek, J; Hofman, O; Reisenauer, R; Slaby, A [Karlova Universita, Prague (Czechoslovakia). Inst. of Biophysics and Nuclear Medicine; Karlova Universita, Prague (Czechoslovakia). IV. Dept. of Internal Medicine; Vyzkumny Ustav Endokrinologicky, Prague [Czechoslovakia

    1977-04-01

    Plasma renin activity (PRA) stimulated by upright posture was measured in 300 men aged 45 to 64 years using a radioimmunoassay of angiotensin-I. The examined subjects were normotensive or patients with benign essential hypertension and were divided into 6 groups according to the absence of manifest atherosclerosis, the presence of definite angina pectoris or a history of myocardial infarction. Each group contained 50 unselected subjects, with a comparable mean age. Significant differences in mean PRA were found between corresponding groups of hypertensives and normotensives, the values in hypertensives being lower. The percentage of low renin values was higher in hypertensives with ischaemic heart disease than in other groups. It is suggested that this finding might be explained by functional disturbances in the kidneys in hypertensives with ischaemic heart disease.

  3. 21 CFR 862.1045 - Aldosterone test system.

    Science.gov (United States)

    2010-04-01

    ... treatment of primary aldosteronism (a disorder caused by the excessive secretion of aldosterone by the adrenal gland), hypertension caused by primary aldosteronism, selective hypoaldosteronism, edematous...

  4. Antihypertensive effects of double the maximum dose of valsartan in African-American patients with type 2 diabetes mellitus and albuminuria

    DEFF Research Database (Denmark)

    Weir, Matthew R; Hollenberg, Norman K; Zappe, Dion H

    2010-01-01

    The blood pressure (BP)-lowering response to renin-angiotensin-aldosterone system blockade in hypertensive African-Americans is typically less than in whites. To determine whether higher than conventional doses of renin-angiotensin-aldosterone system blockade can improve BP reduction in African-A...

  5. Aldosterone and glomerular filtration--observations in the general population.

    Science.gov (United States)

    Hannemann, Anke; Rettig, Rainer; Dittmann, Kathleen; Völzke, Henry; Endlich, Karlhans; Nauck, Matthias; Wallaschofski, Henri

    2014-03-10

    Increasing evidence suggests that aldosterone promotes renal damage. Since data on the association between aldosterone and renal function in the general population are sparse, we chose to address this issue. We investigated the associations between the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) and the estimated glomerular filtration rate (eGFR) in a sample of adult men and women from Northeast Germany. A study population of 1921 adult men and women who participated in the first follow-up of the Study of Health in Pomerania was selected. None of the subjects used drugs that alter PAC or ARR. The eGFR was calculated according to the four-variable Modification of Diet in Renal Disease formula. Chronic kidney disease (CKD) was defined as an eGFR < 60 ml/min/1.73 m2. Linear regression models, adjusted for sex, age, waist circumference, diabetes mellitus, smoking status, systolic and diastolic blood pressures, serum triglyceride concentrations and time of blood sampling revealed inverse associations of PAC or ARR with eGFR (ß-coefficient for log-transformed PAC -3.12, p < 0.001; ß-coefficient for log-transformed ARR -3.36, p < 0.001). Logistic regression models revealed increased odds for CKD with increasing PAC (odds ratio for a one standard deviation increase in PAC: 1.35, 95% confidence interval: 1.06-1.71). There was no statistically significant association between ARR and CKD. Our study demonstrates that PAC and ARR are inversely associated with the glomerular filtration rate in the general population.

  6. Polychlorinated biphenyl 126 stimulates basal and inducible aldosterone biosynthesis of human adrenocortical H295R cells

    International Nuclear Information System (INIS)

    Li, L.-A.; Wang, P.-W.; Chang, Louis W.

    2004-01-01

    To understand the effects of polychlorinated biphenyls (PCBs) on adrenal aldosterone biosynthesis, we have performed a systematical study to characterize the corresponding steroidogenic response of human adrenocortical cell line H295R to PCB126 exposure. We found that PCB126 at high concentrations stimulated basal and inducible aldosterone production. The aldosterone induction occurred concomitantly with activation of the CYP11B2 gene. Despite the fact that PCB126 acted in synergy with both potassium and angiotensin II (Ang II) in activation of aldosterone synthesis, PCB126 only modestly increased CYP11B2 mRNA expression in the presence of Ang II contrary to the synergistic transcriptional induction elicited by PCB126 and potassium. This implicated that PCB126 had differential interactions with the potassium and Ang II signaling systems in the regulation of aldosterone biosynthesis. In addition, high concentrations of PCB126 elevated transcriptional expression of the type I Ang II receptor (AT 1 ) and might thus sensitize the cellular Ang II responsiveness in both basal and inducible aldosterone biosynthesis. SF-1 was not involved in the PCB126-induced transcriptional regulation despite its importance in steroidogenic gene activation

  7. Role of calcium in effects of atrial natriuretic peptide on aldosterone production in adrenal glomerulosa cells

    International Nuclear Information System (INIS)

    Chartier, L.; Schiffrin, E.L.

    1987-01-01

    Atrial natriuretic peptide (ANP) inhibits the stimulation of aldosterone secretion by isolated adrenal glomerulosa cells produced by angiotensin II (ANG II), ACTH, and potassium. The effect of ANP on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium on isolated rat adrenal glomerulosa cells was studied. In the presence of ANP the maximal response of aldosterone output stimulated by ANG II or potassium decreased and the half-maximum (EC 50 ) of the response to ACTH was displaced to the right. Because these effects resemble those of calcium-channel blockers, the authors investigated the effect of different concentrations of nifedipine, a dihydropyridine calcium-channel blocker, on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium. Nifedipine produced effects similar to ANP. The maximal response of aldosterone stimulated by ANG II and potassium was decreased and the dose-response curve to ACTH was displaced to the right. ANP decreased the maximal response of aldosterone to the dihydropyridine derivative BAY K8644, a calcium-channel activator, without change in its EC 50 . In contrast, nifedipine displaced the dose-response curve to BAY K8644 to the right as expected of a competitive inhibitor. The effect of ANP and nifedipine on basal and stimulated 45 Ca influx into isolated rat adrenal glomerulosa cells was studied. ANP may act on the rat adrenal glomerulosa cells at least in part by interference with calcium entry

  8. Angiotensin effects on calcium and steroidogenesis in adrenal glomerulosa cells

    International Nuclear Information System (INIS)

    Elliott, M.E.; Siegel, F.L.; Hadjokas, N.E.; Goodfriend, T.L.

    1985-01-01

    We investigated the role of cellular calcium pools in angiotensin II-stimulated aldosterone synthesis in bovine adrenal glomerulosa cells. Angiotensin II decreased the size of the exchangeable cell calcium pool by 34%, consistent with previous observations that angiotensin II causes decreased uptake of 45 Ca+2 into cells and increased efflux of 45 Ca+2 from preloaded cells. Atomic absorption spectroscopy showed that angiotension II caused a decrease of 21% in total cellular calcium. Angiotensin II caused efflux of 45 Ca+2 in the presence of EGTA and retarded uptake of 45 Ca+2 when choline was substituted for sodium, suggesting that hormone effects on calcium pools do not involve influx of trigger calcium or sodium. Cells incubated in calcium-free buffer and 0.1 mM or 0.5 mM EGTA synthesized reduced (but still significant) amounts of the steroid in response to hormone. Cells incubated in increasing concentrations of extracellular calcium contained increasing amounts of intracellular calcium and synthesized increasing amounts of aldosterone in response to angiotensin II. These results point to the participation of intracellular calcium pools in angiotensin II-stimulated steroidogenesis and the importance of extracellular calcium in maintaining these pools

  9. Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors

    Science.gov (United States)

    Okada, Yoshiyuki; Jarvis, Sara S; Best, Stuart A; Bivens, Tiffany B; Adams-Huet, Beverley; Levine, Benjamin D; Fu, Qi

    2013-01-01

    Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n= 7), or a diuretic, hydrochlorothiazide (n= 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P= 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)−1 pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)−1; P= 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)−1), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)−1; P= 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P= 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r= 0.74, P= 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin–angiotensin–aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive

  10. A novel interaction between sympathetic overactivity and aberrant regulation of renin by miR-181a in BPH/2J genetically hypertensive mice.

    Science.gov (United States)

    Jackson, Kristy L; Marques, Francine Z; Watson, Anna M D; Palma-Rigo, Kesia; Nguyen-Huu, Thu-Phuc; Morris, Brian J; Charchar, Fadi J; Davern, Pamela J; Head, Geoffrey A

    2013-10-01

    Genetically hypertensive mice (BPH/2J) are hypertensive because of an exaggerated contribution of the sympathetic nervous system to blood pressure. We hypothesize that an additional contribution to elevated blood pressure is via sympathetically mediated activation of the intrarenal renin-angiotensin system. Our aim was to determine the contribution of the renin-angiotensin system and sympathetic nervous system to hypertension in BPH/2J mice. BPH/2J and normotensive BPN/3J mice were preimplanted with radiotelemetry devices to measure blood pressure. Depressor responses to ganglion blocker pentolinium (5 mg/kg i.p.) in mice pretreated with the angiotensin-converting enzyme inhibitor enalaprilat (1.5 mg/kg i.p.) revealed a 2-fold greater sympathetic contribution to blood pressure in BPH/2J mice during the active and inactive period. However, the depressor response to enalaprilat was 4-fold greater in BPH/2J compared with BPN/3J mice, but only during the active period (P=0.01). This was associated with 1.6-fold higher renal renin messenger RNA (mRNA; P=0.02) and 0.8-fold lower abundance of micro-RNA-181a (P=0.03), identified previously as regulating human renin mRNA. Renin mRNA levels correlated positively with depressor responses to pentolinium (r=0.99; P=0.001), and BPH/2J mice had greater renal sympathetic innervation density as identified by tyrosine hydroxylase staining of cortical tubules. Although there is a major sympathetic contribution to hypertension in BPH/2J mice, the renin-angiotensin system also contributes, doing so to a greater extent during the active period and less during the inactive period. This is the opposite of the normal renin-angiotensin system circadian pattern. We suggest that renal hyperinnervation and enhanced sympathetically induced renin synthesis mediated by lower micro-RNA-181a contributes to hypertension in BPH/2J mice.

  11. Aldosterone synthase C-344T, angiotensin II type 1 receptor ...

    Indian Academy of Sciences (India)

    2014-12-26

    Dec 26, 2014 ... other causes of secondary hypertension), diabetes or under any kind of .... used for the analysis of CYP11B2 C-344T and ATR1 A1166C ...... Staessen J. A., Li Y. and Thijs L. 2007 Meta-analysis of blood pres- sure and the ...

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

    African Journals Online (AJOL)

    Chibuike

    high fat, high sugar, low fibre diet – is another modifiable risk factor for .... identifying appropriate proteolytic enzymes and food protein raw materials, based on .... consumption of milk protein hydrolysates enriched with the LTPs,. IPP/VPP ...

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

    NARCIS (Netherlands)

    Harst, Pim van der

    2006-01-01

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

  14. Therapeutic targets of renin-angiotensin system in ocular disorders

    Directory of Open Access Journals (Sweden)

    Rajesh Choudhary

    2017-03-01

    Conclusions: The RAS components are present in the extrarenal tissues including ocular tissue and have an imperative role in the ocular pathophysiology. The clinical studies are needed to show the role of therapeutic modalities targeting RAS in the treatment of different ocular disorders.

  15. Renin-angiotensin system in human coronavirus pathogenesis

    NARCIS (Netherlands)

    Wevers, Brigitte A.; van der Hoek, Lia

    2010-01-01

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

  16. Aldosterone synthase gene polymorphism in alimentary obesity, metabolic syndrome components, some secondary forms of arterial hypertension, pathology of the adrenals glands core (literature review

    Directory of Open Access Journals (Sweden)

    S.N. Koval

    2017-08-01

    populations. Europeans, Asians, Africans and North Americans were among them and were genotyped by CYP11B2. To date, there is ample evidence that fatty tissue (FT, apart from a source of energy, is an active endocrine organ that plays a key role in maintaining homeostasis and participating in the pathogenesis of a number of diseases. Its excess is accompanied by hyperactivation of tissue renin-angiotensin-aldosterone system (RAAS, strengthening of local and systemic synthesis of AL and the emergence of secondary aldosteronism. AL, in its turn, has a direct effect on FT due to increased MKR density expressed on adipocytes surface, leading to acceleration in the maturation of the latter and a further increase in FT. Getting into the systemic blood circulation and effecting other organs, the excess AL promotes the development of insulin resistance, atherosclerosis, the progression of systemic inflammatory reactions. MKR activation in FT plays not only the key role in sodium reabsorption by kidneys and the control of BP, but also in the differentiation of preadipocytes into mature adipocytes in FT, induction of inflammation and hyperproduction of cytokines — tumor necrotic factor alpha (TNF-α, monocyte chemotactic protein (MCP-1 and interleukin 6 (IL-6 in the white FT, a decrease in the thermogenic activity and trans­cription of the uncoupling protein-1 (UCP-1 in brown FT. MCR hyperactivation was detected in mice with AO (obese db/db mice, associated with increased BMI in humans and contributes to the development of IR and associated with AO cardiovascular diseases. The gene polymorphism of AS may be a marker of aggravated pregnancy, the presence of gestational hypertension or pre-eclampsia. Some studies found that AS gene polymorphism can affect plasma glucose levels. AS gene polymorphism was not associated with the progression of diabetic nephropathy (DN, but is associated with AH in persons with type 2 diabetes mellitus. National authors conclude about the association

  17. Fundamental and clinical study of direct immunoradiometric assay in human renin concentration

    International Nuclear Information System (INIS)

    Kurimoto, Fumihiko; Horiuchi, Junko; Sakurai, Hyoichiro; Suzuki, Hiromichi; Takita, Takashi; Saruta, Takao.

    1988-01-01

    'Renin RIA Pasteur' kit for directly measuring renin concentration in human plasma (PRC) was fundamentally and clinically evaluated. A standard curve for PRC was linear in the range of 10 - 640 pg/ml. Reproducibility, recovery, and stability were satisfactory. There was a significantly positive correlation between direct PRC and conventional plasma renin activity (PRA) and indirect PRC. PRC was directly measured in 119 healthy volunteers and 15 patients with primary aldosteronism (4), Cushing's syndrome (6), or non-functioning tumor (5). The basal PRC was 32.4 +- 18.8 pg/ml for men and 37.9 +- 22.6 pg/ml for women. PRC for primary aldosteronism was below detectable levels, and remained unchanged even after the administratin of ACTH. In the case of Cushing's syndrome, mean PRC and PRA were 19 pg/ml and 1.2 ng/ml/hr, and did not respond to ACTH. Although the administration of ATCH was significantly associated with a decreased PRC, there was only tendency toward the decreased PRA in the case of non-functioning tumors. The results indicate the usefulness of the present kit in terms of its ability to directly measure PRC without any complicated procedures. (Namekawa, K.)

  18. Effects of angiotensin II receptor blockade on cerebral, cardiovascular, counter-regulatory, and symptomatic responses during hypoglycaemia in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Færch, Louise H; Thorsteinsson, Birger; Tarnow, Lise

    2015-01-01

    INTRODUCTION: High spontaneous activity of the renin-angiotensin system (RAS) results in more pronounced cognitive impairment and more prolonged QTc interval during hypoglycaemia in type 1 diabetes. We tested whether angiotensin II receptor blockade improves cerebral and cardiovascular function d...

  19. Dietary sodium modulation of aldosterone activation and renal function during the progression of experimental heart failure.

    Science.gov (United States)

    Miller, Wayne L; Borgeson, Daniel D; Grantham, J Aaron; Luchner, Andreas; Redfield, Margaret M; Burnett, John C

    2015-02-01

    Aldosterone activation is central to the sodium–fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: (i) high sodium [250 mEq (5.8 g) per day, n =6]; (ii) standard sodium [58 mEq (1.3 g) per day, n =6]; and (iii) sodium restriction [11 mEq (0.25 g) per day, n =6]. During the 38-day study, haemodynamics, renal function, plasma renin activity (PRA), and aldosterone were measured. Changes in haemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups; however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression.

  20. Aldosterone and cortisol co-secreting bifunctional adrenal cortical carcinoma: A rare event

    Directory of Open Access Journals (Sweden)

    Puskar Shyam Chowdhury

    2014-01-01

    Full Text Available Adrenocortical carcinoma (ACC co-secreting aldosterone and cortisol is extremely rare. We report the case of a 37-yearold female who presented with paresis and facial puffiness. Evaluation revealed hypertension, hyperglycemia, severe hypokalemia and hyperaldosteronemia with elevated plasma aldosterone to renin ratio (ARR. Urinary free cortisol estimation showed elevated levels. Computed tomography scan revealed a right adrenal mass. Radical adrenalectomy specimen revealed ACC (T3N1. Post-operatively, the patient became normotensive and euglycemic with normalization of urinary cortisol and ARR. This case highlights the need for a complete evaluation in patients of hyperaldosteronism if overlapping symptoms of hypercortisolism are encountered, to avoid post-operative adrenal crisis.

  1. Impact of angiotensin II on skeletal muscle metabolism and function in mice: contribution of IGF-1, Sirtuin-1 and PGC-1α.

    Science.gov (United States)

    Kackstein, Katharina; Teren, Andrej; Matsumoto, Yasuharu; Mangner, Norman; Möbius-Winkler, Sven; Linke, Axel; Schuler, Gerhard; Punkt, Karla; Adams, Volker

    2013-05-01

    Activation of the renin-angiotensin-aldosterone system and increased levels of angiotensin II (Ang-II) occurs in numerous cardiovascular diseases such as chronic heart failure (CHF). Another hallmark in CHF is a reduced exercise tolerance with impaired skeletal muscle function. The aim of this study was to investigate in an animal model the impact of Ang-II on skeletal muscle function and concomitant molecular alterations. Mice were infused with Ang-II for 4 weeks. Subsequently, skeletal muscle function of the soleus muscle was assessed. Expression of selected proteins was quantified by qRT-PCR and Western blot. Infusion of Ang-II resulted in a 33% reduction of contractile force, despite a lack of changes in muscle weight. At the molecular level an increased expression of NAD(P)H oxidase and a reduced expression of Sirt1, PGC-1α and IGF-1 were noticed. No change was evident for the ubiquitin E3-ligases MuRF1 and MafBx and α-sarcomeric actin expression. Cytophotometrical analysis of the soleus muscle revealed a metabolic shift toward a glycolytic profile. This study provides direct evidence of Ang-II-mediated, metabolic deterioration of skeletal muscle function despite preserved muscle mass. One may speculate that the Ang-II-mediated loss of muscle force is due to an activation of NAD(P)H oxidase expression and a subsequent ROS-induced down regulation of IGF-1, PGC-1α and Sirt1. Copyright © 2012 Elsevier GmbH. All rights reserved.

  2. Angiotensin receptor blockers: Focus on cardiac and renal injury.

    Science.gov (United States)

    Arumugam, Somasundaram; Sreedhar, Remya; Thandavarayan, Rajarajan A; Karuppagounder, Vengadeshprabhu; Krishnamurthy, Prasanna; Suzuki, Kenji; Nakamura, Masahiko; Watanabe, Kenichi

    2016-04-01

    Angiotensin II, an important component of renin angiotensin system, is a potent vasopressor and its actions are mostly mediated via angiotensin II type 1 receptor (AT1R) and role of AT2R in counterbalancing the actions of AT1R stimulation are under extensive research. In addition to its physiological actions, angiotensin II plays important roles in the pathogenesis of atherosclerosis, hypertension, left ventricular hypertrophy, and heart failure. The effects of angiotensin II can be blocked by either suppressing its production by blocking angiotensin converting enzyme or by antagonizing its actions on AT1R using angiotensin II receptor blockers (ARBs). Instead of the extensive use of ARBs in the treatment of various cardiovascular diseases, proper selection of a particular ARB is crucial as the clinical condition of individual patient is different and also their economic status would play an essential role in medication compliance. Thus a critical review of the proven and promising actions of ARBs against various pathological conditions will be of great importance for the clinicians as well as for the researchers. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Aliskiren suppresses the renin–angiotensin–aldosterone system and reduces blood pressure and albuminuria in elderly chronic kidney disease patients with hypertension

    Directory of Open Access Journals (Sweden)

    Morishita Y

    2012-09-01

    Full Text Available Yoshiyuki Morishita,1 Toshihiro Yasui,2 Akihiko Numata,1 Akira Onishi,1 Kenichi Ishibashi,3 Eiji Kusano11Department of Internal Medicine, Jichi Medical University, Shimotsuke, Japan; 2National Health Insurance Yukawa Clinic, Niimi, Japan; 3Department of Medical Physiology, Meiji Pharmaceutical University, Tokyo, JapanBackground: We investigated the effects of aliskiren in terms of its inhibition of the renin–angiotensin–aldosterone system (RAAS as well as that on blood pressure (BP, and renal and cardiac protection in elderly chronic kidney disease (CKD patients with hypertension.Methods: Nineteen elderly CKD patients (nine males, ten females, aged 74.6 ± 5.8 years were assigned to receive 150 mg/day of aliskiren added to existing antihypertensives for 6 months. Changes in plasma renin activity (PRA, angiotensin I (Ang I, angiotensin II (Ang II, aldosterone (Ald, BP, estimated glomerular filtration rate (eGFR, urine albumin/creatinine ratio (UACR, left ventricular ejection fraction (LVEF, interventricular septum thickness (IVST, left ventricular posterior wall thickness (LVPWT, and plasma brain natriuretic peptide (BNP levels were evaluated.Results: Aliskiren suppressed the RAAS as follows: PRA 1.3 ± 1.0 to 0.3 ± 0.3 ng/mL/hour, P < 0.05; Ang I 59.5 ± 32.1 to 26.0 ± 17.3 pg/mL, P < 0.05; Ang II 58.4 ± 62.1 to 14.3 ± 9.0 pg/mL, P < 0.05; and Ald 86.1 ± 38.3 to 80.1 ± 52.6 pg/mL, not significant (NS. Aliskiren reduced BP (153.6/77.2 ± 14.9/10.4 to 130.9/72.2 ± 15.6/9.9 mmHg, P < 0.05. It also reduced UACR (747.1 ± 1121.4 to 409.6 ± 636.8 mg/g, P < 0.05, whereas it did not change eGFR (52.1 ± 29.2 to 51.2 ± 29.3 mL/min/1.73 m2, NS, LVEF (66.8 ± 7.9 to 66.5% ± 6.8%, NS, IVST (10.1 ± 1.8 to 9.9 ± 1.8 mm, NS, LVPWT (10.0 ± 1.6 mm to 10.0 ± 1.4 mm, NS, or BNP (48.2 ± 46.0 to 54.9 ± 41.1 pg/mL, NS.Conclusion: Aliskiren was effective for BP control and reduced UACR while maintaining eGFR and heart function in elderly CKD

  4. Normotensive sodium loading in normal man: Regulation of renin secretion during beta-receptor blockade

    DEFF Research Database (Denmark)

    Mølstrøm, Simon; Larsen, Nils Heden;