Dataset Information

Blood pressure response to angiotensin II is enhanced in obese Zucker rats and is attributed to an aldosterone-dependent mechanism.

ABSTRACT: BACKGROUND AND PURPOSE: Plasma aldosterone levels correlate positively with obesity, suggesting a link between the hypertension associated with obesity and increased mineralocorticoid levels. We tested the hypothesis that aldosterone is involved in the BP response to angiotensin II (AngII) in obese rats. EXPERIMENTAL APPROACH: Lean (LZR) and obese (OZR) Zucker rats were treated with AngII (9 µg·h(-1) ; 4 weeks), and BP and plasma AngII and aldosterone were determined. KEY RESULTS: Chronic AngII increased the BP in OZR markedly more so than in LZR. Plasma AngII levels in LZR and OZR were similar after AngII treatment. The AngII stimulated a rise in plasma aldosterone that was sixfold more in OZR than in LZR. The thickness of the zona glomerulosa of the adrenal glands was selectively increased by AngII in OZR. Adrenal mRNA levels of CYP11B2 aldosterone synthase and the AT(1B) receptor were selectively increased in AngII-treated OZR. The BP response to chronic AngII stimulation was diminished in OZR after adrenalectomy when plasma aldosterone was absent. Acute bolus injections of AngII did not increase the BP response or aldosterone release in OZR. CONCLUSIONS AND IMPLICATIONS: The AngII-induced BP response is enhanced in obesity and this is associated with a specific increase in circulating aldosterone. Due to the AngII-induced growth of the zona glomerulosa in OZR, the AT(1B) receptors and aldosterone synthase may be selectively enhanced in obesity under concomitant AngII stimulation, increasing the adrenal synthesis of aldosterone. Our results confirm functionally that aldosterone plays a major role in obesity-related hypertension.

SUBMITTER: Muller-Fielitz H

PROVIDER: S-EPMC3448903 | biostudies-other | 2012 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Blood pressure response to angiotensin II is enhanced in obese Zucker rats and is attributed to an aldosterone-dependent mechanism.

Müller-Fielitz Helge H Lau Margot M Jöhren Olaf O Stellmacher Florian F Schwaninger Markus M Raasch Walter W

British journal of pharmacology 20120801 8

<h4>Background and purpose</h4>Plasma aldosterone levels correlate positively with obesity, suggesting a link between the hypertension associated with obesity and increased mineralocorticoid levels. We tested the hypothesis that aldosterone is involved in the BP response to angiotensin II (AngII) in obese rats.<h4>Experimental approach</h4>Lean (LZR) and obese (OZR) Zucker rats were treated with AngII (9 µg·h(-1) ; 4 weeks), and BP and plasma AngII and aldosterone were determined.<h4>Key results ...[more]

PMID: 22452651

Similar Datasets

Project description:Both angiotensin II type 1 receptor (AT1R) and nuclear factor-kappa B (NF-?B) play significant roles in the pathogenesis of hypertension and type 2 diabetes. However, the role of NF-?B in perpetuating renal AT1 receptors dysfunction remains unclear. The aim of the present study to determine whether blockade of NF-?B, could reverse the exaggerated renal AT1R function, reduce inflammatory state and oxidative stress, lower blood pressure in Zucker diabetic fatty (ZDF) rats.Pyrrolidine dithiocarbamate (PDTC), a NF-?B inhibitor (150 mg/kg in drinking water)or vehicle was administered orally to 12-weeks-old ZDF rats and their respective control lean Zucker (LZ) rats for 4 weeks. Blood pressure was measured weekly by tail-cuff method. AT1R functions were determined by measuring diuretic and natriuretic responses to AT1R antagonist (candesartan; 10 ?g/kg/min iv). The mRNA and protein levels of NF-?B, oxidative stress maker and AT1R were determined using quantitative real-time PCR and Western blotting, respectively. The NF-?B-DNA binding activity in renal cortex was measured by Electrophoretic mobility shift assay (EMSA).As compared with LZ rats, ZDF rats had higher blood pressure, impaired natriuresis and diuresis, accompanied with higher levels of oxidative stress and inflammation. Furthermore, AT1R expression was higher in renal cortex from ZDF rats; candesartan induced natriresis and diuresis, which was augmented in ZDF rats. Treatment with PDTC lowered blood pressure and improved diuretic and natriuretic effects in ZDF rats; meanwhile, the increased oxidative stress and inflammation were reduced; the increased AT1R expression and augmented candesartan-mediated natriuresis and diuresis were recoverd in ZDF rats. Our further study investigated the mechanisms of PDTC on AT1R receptor expression. It resulted that PDTC inhibited NF-?B translocation from cytosol to nucleus, inhibited binding of NF-?B with AT1R promoter, therefore, reduced AT1R expression and function.Our present study indicates blockade of NF-?B, via inhibition of binding of NF-?B with AT1R promoter, reduces renal AT1R expression and function, improves oxidative stress and inflammatory/anti-inflammatory balance, therefore, lowers blood pressure and recovers renal function in ZDF rats.

Dataset Information

Blood pressure response to angiotensin II is enhanced in obese Zucker rats and is attributed to an aldosterone-dependent mechanism.

Publications

Blood pressure response to angiotensin II is enhanced in obese Zucker rats and is attributed to an aldosterone-dependent mechanism.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets