Mechanisms of Adrenomedullin-Induced Vasodilation in the Rat Kidney

Abstract

To explore the mechanisms of adrenomedullin-induced vasorelaxation, we tested the effects of adrenomedullin on renal function in rats in vivo and measured the release of endothelium-derived nitric oxide from isolated perfused rat kidney (using a chemiluminescence assay) and the diameters of the glomerular arterioles in the hydronephrotic kidney. Adrenomedullin decreased blood pressure in a dose-dependent manner (3 nmol/kg: −29±2% [SEM]; P<.01) and slightly increased the glomerular filtration rate and urinary sodium excretion (+108%; P<.05). These changes were associated with significant increases in urinary excretion of cyclic AMP (+54%; P<.05). Adrenomedullin decreased renal vascular resistance (10−7 mol/L adrenomedullin: −41±2%; P<.001) and increased release of nitric oxide (+5.1±0.7 fmol/min per gram kidney weight; P<.001) in the isolated kidney. This increase in nitric oxide release was abolished by the inhibitor NG-monomethyl-l-arginine, and it also reversed the decrease in renal vascular re...