Mechanisms of adrenomedullin-induced vasodilation in the rat kidney

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1995-04, Vol.25 (4), p.790-795
• Main Authors: HIRATA, Y, HAYAKAWA, H, MATSUO, H, OMATA, M, SUZUKI, Y, SUZUKI, E, IKENOUCHI, H, KOHMOTO, O, KIMURA, K, KITAMURA, K, ETO, T, KANGAWA, K
• Format: Article
• Language: English
• Subjects: Adrenomedullin; Animals; Antihypertensive Agents - pharmacology; Arterial hypertension. Arterial hypotension; Arterioles - drug effects; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Calcium - metabolism; Cardiology. Vascular system; Experimental diseases; Kidney - drug effects; Kidney - metabolism; Kidney Glomerulus - blood supply; Medical sciences; Nitric Oxide - metabolism; Peptides - pharmacology; Rats; Rats, Wistar; Renal Circulation - drug effects; Vasodilation
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.25.4.790

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.