Rapid Nongenomic Effects of Aldosterone on the Renal Vasculature in Humans

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Abstract
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 μg) 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 andpara-aminohippuric acid. Injection of aldosterone without concomitant infusion ofl-NMMA changed the renal plasma flow and glomerular filtration rate not statistically significant compared with placebo. Coinfusion ofl-NMMA unmasked the effect of aldosterone: aldosterone withl-NMMA decreased the glomerular filtration rate slightly (−1.4±6.2 mL/min), whereas infusion ofl-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 withl-NMMA decreased renal plasma flow by 190.0±213.7 mL/min (P=0.074). Accordingly, Aldosterone withl-NMMA increased renal vascular resistance much more thanl-NMMA alone (1588±237 versus 614±240 dyn×s×cm−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.