Document Detail


Blood pressure response to angiotensin II is enhanced in obese Zucker rats and is attributed to an aldosterone-dependent mechanism.
MedLine Citation:
PMID:  22452651     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Helge Müller-Fielitz; Margot Lau; Olaf Jöhren; Florian Stellmacher; Markus Schwaninger; Walter Raasch
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  166     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-24     Completed Date:  2012-12-10     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2417-29     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Affiliation:
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adrenalectomy
Aldosterone / metabolism*
Angiotensin II / pharmacology*
Animals
Blood Pressure / drug effects*
Hypertension / chemically induced*
Male
Obesity / metabolism*
Rats
Rats, Zucker
Chemical
Reg. No./Substance:
11128-99-7/Angiotensin II; 52-39-1/Aldosterone
Comments/Corrections

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