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 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.
Hirata
Y
Y
Second Department of Internal Medicine, University of Tokyo, Japan.
Hayakawa
H
H
Suzuki
Y
Y
Suzuki
E
E
Ikenouchi
H
H
Kohmoto
O
O
Kimura
K
K
Kitamura
K
K
Eto
T
T
Kangawa
K
K
D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply; D009569:Nitric Oxide / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*; D014664:Vasodilation
D000959:Antihypertensive Agents; D010455:Peptides; D053607:Adrenomedullin; D009569:Nitric Oxide; D002118:Calcium