Rapid non-genomic effects of aldosterone on the renal vasculature.
There is increasing evidence for the importance of rapid non-genomic effects of aldosterone on the human vasculature including renal vessels. Arima and colleagues by examining isolated perfused afferent and efferent arterioles from rabbit kidneys found a vasoconstriction in both. In another study the same group showed that endothelium-derived nitric oxide (NO) modulates the vasoconstrictor response to aldosterone in rabbit preglomerular afferent arterioles. Disrupting the endothelium as well as blockade of endothelial NO synthase (eNOS) augmented aldosterone-induced vasoconstriction in this study. Uhrenholt et al. found no effect of aldosterone alone to afferent arterioles but a suppression of depolarisation-induced vasoconstriction. After the blockade of eNOS the aldosterone effect was completely suppressed. In a clinical study in healthy male volunteers injection of aldosterone had no statistically significant effects. Co-infusion of the eNOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA) changed the effect of aldosterone on renal hemodynamics. Aldosterone in co-infusion with L-NMMA decreased renal plasma flow (RPF) much stronger than L-NMMA alone. Infusion of L-NMMA alone increased GFR whereas aldosterone/L-NMMA lowered GFR slightly. Aldosterone co-infused with L-NMMA strongly increased renal vascular resistance (RVR). The increase was on top of the smaller increase that was induced by L-NMMA infusion. These data indicate that aldosterone acts via rapid non-genomic effects in vivo in humans at the renal vasculature. Antagonizing the endothelial nitric oxide synthase unmasks these effects. Therefore, rapid non-genomic aldosterone effects increase renal vascular resistance and thereby may mediate arterial hypertension if endothelial dysfunction is present.
Schmidt
Bernhard M W
BM
Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054 Erlangen, Germany. bernhardmwschmidt@yahoo.com
D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001783:Blood Flow Velocity; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000473:pathology; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010477:Perfusion; D011817:Rabbits; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019323:omega-N-Methylarginine; D000450:Aldosterone; D052250:Nitric Oxide Synthase Type III