Aldosterone blunts human baroreflex sensitivity by a nongenomic mechanism.
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 microg/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.


CONCLUSIONS
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.
Schmidt
B M W
BM
Institute of Clinical Pharmacology, University Hospital of Mannheim, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany. bernhardmwschmidt@yahoo.com
Horisberger
K
K
Feuring
M
M
Schultz
A
A
Wehling
M
M
D000328:Adult; D000450:Aldosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure; D002191:Canrenoic Acid / Q000008:administration & dosage; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007700:Kinetics; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage; D010919:Placebos
D000451:Mineralocorticoid Receptor Antagonists; D010919:Placebos; D000450:Aldosterone; D002191:Canrenoic Acid