There is increasing evidence for the importance of rapid nongenomic effects of aldosterone on the human vasculature. In vitro animal experiments in renal arterioles also suggest the presence of such effects on the renal vasculature. We conducted a clinical study to explore these effects in vivo in humans. Thirteen healthy male volunteers were examined. Aldosterone (500 microg) or placebo was injected intravenously with or without coinfusion of N(G) monomethyl-L-arginine (L-NMMA) in a randomized, double-blinded 4-fold crossover design. Renal plasma flow and glomerular filtration rate were measured by constant infusion clearance technique using inulin and para-aminohippuric acid. Injection of aldosterone without concomitant infusion of L-NMMA changed the renal plasma flow and glomerular filtration rate not statistically significant compared with placebo. Coinfusion of L-NMMA unmasked the effect of aldosterone: aldosterone with L-NMMA decreased the glomerular filtration rate slightly (-1.4+/-6.2 mL/min), whereas infusion of L-NMMA alone increased the glomerular filtration rate (8.3+/-9.8 mL/min; P=0.004). L-NMMA alone decreased renal plasma flow by 58.2+/-97.5 mL/min, and aldosterone with L-NMMA decreased renal plasma flow by 190.0+/-213.7 mL/min (P=0.074). Accordingly, Aldosterone with L-NMMA increased renal vascular resistance much more than L-NMMA alone (1588+/-237 versus 614+/-240 dynxsxcm(-5); P=0.014). These data indicate that aldosterone acts via rapid nongenomic effects in vivo in humans at the renal vasculature. Antagonizing the endothelial NO synthase unmasks these effects. Therefore, rapid nongenomic aldosterone effects increase renal vascular resistance and thereby mediate arterial hypertension if endothelial dysfunction is present.