The effect of aldosterone on adipocyte-derived relaxation occurs via non-genomic and genomic effects on the vasculature

King's College London (2008) Proc Physiol Soc 13, PC43

Poster Communications: The effect of aldosterone on adipocyte-derived relaxation occurs via non-genomic and genomic effects on the vasculature

C. Agabiti-Rosei1, S. Withers1, A. Greenstein1, R. Aslam1, K. Khavandi1, K. Sonoyama1, R. Malik1, A. Heagerty1

1. Medicine, University of Manchester, Manchester, United Kingdom.

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Introduction: There is increasing evidence suggesting a link between aldosterone and components of the metabolic syndrome, particularly abdominal obesity and arterial hypertension. We have shown that the anticontractile property of perivascular adipose tissue is lost in patients with this syndrome; the aim of this study was to investigate whether aldosterone was able to influence this anticontractile response and whether this was due to genomic or non-genomic effects and if any influence could be reversed. Methods: Small arterial segments (2mm, <200µm internal diameter) were dissected from healthy male wistar rats and studied using wire myography. The effects of aldosterone and its non-genomic and genomic antagonists, eplerenone and spironolactone respectively, were assessed under normoxic conditions following short and long incubations (10min and 3hours). Contractile responses to noradrenaline were calculated as a percentage of KCl contraction, and expressed as mean±SEM. Results: Adipose tissue exhibited an anti-contractile effect on arteries (no adipocytes: 136±6% vs adipocytes 87±4%, n=10, P<0.0001) which was lost following 10min incubation with aldosterone (5nM) (adipocytes: 87±4%, n=10 vs. adipocytes + aldosterone: 124±6% n=9, P<0.001). Short incubation with eplerenone, but not spironolactone, restored the contractility to levels similar to arteries with adipocytes alone (88±3%, n=6). Three hour incubation of aldosterone caused a loss of the anti-contractile effect similar to that observed with short incubation (134±5%, n=3) however, both eplerenone and spironolactone were only able to partially restore this effect (adipocytes + 3hr aldosterone: 134±5% vs. adipocytes + 3hr aldosterone + eplerenone: 122±2%, n=3, P=0.0358, adipocytes + 3hr aldosterone + spironolactone: 102±6%, n=3). Contractility of arteries without adipocytes was not significantly affected by any intervention. Conclusion: Aldosterone ameliorates the anticontractile effect of adipose tissue via a predominantly non-genomic effect, because eplerenone can only partially restore contractility following longer incubations. Whether a combination of eplerenone and spironolactone is able to fully restore the effects of aldosterone on contractility is yet to be established.



Where applicable, experiments conform with Society ethical requirements.

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