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
References
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