Rapid nongenomic effects of aldosterone on human forearm vasculature.
The impact of aldosterone in cardiovascular disease and hypertension has recently gained new interest. Aldosterone is now suggested to be a more common cause of hypertension than previously believed and has been linked to myocardial fibrosis, independent of its hypertensive effects. Finally, rapid nongenomic aldosterone effects have been proposed to be important in hypertension, in addition to its genomic effects. Forty-eight healthy male volunteers were examined in a randomized, placebo-controlled, double-blind crossover trial to elucidate the rapid nongenomic, vascular effects of aldosterone in humans. Forearm blood flow was measured by venous occlusion plethysmography. First, aldosterone (500 ng/min) and placebo were infused into the brachial artery for 8 minutes. The volunteers then received ascending doses of acetylcholine, NG-monomethyl-L-arginine (L-NMMA), sodium nitroprusside, or phenylephrine. Aldosterone increased forearm blood flow (P<0.001, ANOVA). The maximum effect was an increase in forearm blood flow with aldosterone of 7.9+/-2.6% compared with 0.1+/-1.9% with placebo treatment after 8 minutes. With aldosterone, L-NMMA induced a greater vasoconstriction (P<0.05, ANOVA), sodium nitroprusside induced an attenuated vasoconstriction (P<0.01, ANOVA), and phenylephrine induced an exaggerated vasoconstriction (P<0.01, ANOVA) within minutes as compared with placebo. These data suggest that aldosterone acts through rapid nongenomic effects at the endothelium by increasing NO release and at the vascular smooth muscle cells by promoting vasoconstriction. This is consistent with in vitro data showing an increase in intracellular calcium in both cell types. Disturbances of these aldosterone effects on both levels might be important in promoting hypertension.
Schmidt
Bernhard M W
BM
Department of Medicine IV/Nephrology, University of Erlangen-Nürnberg, Germany.
Oehmer
Sebastian
S
Delles
Christian
C
Bratke
Renate
R
Schneider
Markus P
MP
Klingbeil
Arnfried
A
Fleischmann
Erwin H
EH
Schmieder
Roland E
RE
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005542:Forearm / Q000098:blood supply; D016678:Genome; D006801:Humans; D007700:Kinetics; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000097:blood / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D000450:Aldosterone; D000109:Acetylcholine