MECHANISMS OF ADRENOMEDULLIN-INDUCED VASODILATION IN THE RAT-KIDNEY

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 N-G-monomethyl-L-arginine, and it also reversed the decrease in renal Vascular resistance seen with adrenomedullin. Renal responses of deoxycorticosterone acetate-salt hypertensive rats to adrenomedullin were significantly smaller than those of control rats for both release of nitric oxide (10(-7) mol/L adrenomedullin: +0.8+/-0.2 fmol/min per gram kidney weight; P<.01 versus control) and renal vasodilation (-28+/-6%; P<.05). Videomicroscopic analysis revealed that adrenomedullin increased the diameters of both afferent and efferent arterioles (3 nmol/kg: +11%; P<.05). Thus, adrenomedullin-induced renal vasodilation is partially endothelium dependent and is attenuated in deoxycorticosterone acetate-salt hypertension, probably due to endothelial damage.