(Hypertension. 1995;25:790-795.)
© 1995 American Heart Association, Inc.
Articles |
Mechanisms of Adrenomedullin-Induced Vasodilation in the Rat Kidney
From the Second Department of Internal Medicine, University of Tokyo (Y.H., H.H., Y.S., E.S., H.I., O.K., K. Kimura, M.O.); the First Department of Internal Medicine, Miyazaki Medical College, Miyazaki (K. Kitamura, T.E.); and Research Institute of National Cardiovascular Center, Osaka (K. Kangawa, H.M.), Japan.
Correspondence to Yasunobu Hirata, MD, Second Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
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 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.
Key Words: calcium • nitric oxide • arteriole • endothelium • vasodilation
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