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Exp Clin Endocrinol Diabetes 2005; 113(5): 252-256
DOI: 10.1055/s-2005-837650
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Aldosterone Blunts Human Baroreflex Sensitivity by a Nongenomic Mechanism

B. M. W. Schmidt1 , 2 , K. Horisberger1 , M. Feuring1 , A. Schultz1 , M. Wehling1
  • 1Institute of Clinical Pharmacology, University Hospital of Mannheim, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany
  • 2Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Nürnberg, Germany
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Publication History

Received: February 23, 2004 First decision: May 3, 2004

Accepted: December 4, 2004

Publication Date:
30 May 2005 (online)

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Abstract

Background: Impaired baroreflex sensitivity (BRS) is a negative predictive factor of mortality in cardiovascular disease. Aldosterone has been shown to decrease BRS in humans and animal models. However, the mode of aldosterone action, whether genomic or nongenomic has not been determined. Therefore, we conducted a clinical study to examine whether BRS, as measured by the phenylephrine method, is impaired in humans by aldosterone by a nongenomic mechanism. Methods: In a randomised, double-blinded, fourfold cross-over trial in 16 healthy male volunteers, BRS was tested 15 minutes after initiation of a continuous infusion of aldosterone (3 µg/minute) or placebo. 6 hours earlier, this period was preceded by an injection of either canrenoate (400 mg) or placebo. Results: BRS was 34.6 ± 4.7 ms/mm Hg in the placebo/placebo period. It was significantly blunted in the placebo/aldosterone (25.5 ± 1.8 ms/mm Hg) as well as in the canrenoate/placebo (24.0 ± 1.5 ms/mm Hg) and the canrenoate/aldosterone (25.4 ± 2.5 ms/mm Hg) periods. Conclusion: These data suggest that the decreased BRS caused by aldosterone is due to a rapid, thus presumably nongenomic mechanism, as these effects occur in a time frame that excludes genomic aldosterone effects at large. The mineralocorticoid receptor (MR) antagonist canrenoate does not block these effects, but blunts BRS by itself.

Key words

Aldosterone - nongenomic effects - baroreflex sensitivity

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MD Bernhard M. W. Schmidt

Medical Department IV/4,
University of Erlangen-Nürnberg
Klinikum Nürnberg Süd

Breslauer Straße 201

90471 Nürnberg

Germany

Phone: + 499113985124

Fax: + 49 91 13 98 31 83

Email: bernhardmwschmidt@yahoo.com

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