Attenuation of adrenomedullin-induced renal vasodilatation by NG-nitro L-arginine but not glibenclamide.
1. The present study was conducted in order to elucidate the in vivo contribution of nitric oxide (NO) and the glibenclamide-sensitive potassium channel in the renal action of adrenomedullin in anaesthetized dogs. 2. Intrarenal arterial infusion of adrenomedullin (20 ng kg-1 min-1) elicited a pronounced increase in renal blood flow with no changes in systemic blood pressure. The renal vasodilator action of adrenomedullin was markedly attenuated by pretreatment with NG-nitro L-arginine (L-NOARG), but this was reversed by continuous infusion of L-arginine. 3. Pretreatment with glibenclamide almost completely blocked the renal vasodilatation induced by lemakalim, but had no effect on the renal vasodilator and diuretic action of adrenomedullin. 4. Intrarenal arterial infusion of adrenomedullin induced diuresis and natriuresis. Diuretic and natriuretic action of adrenomedullin was also attenuated by L-NOARG. L-Arginine partly reversed the effect of L-NOARG and adrenomedullin-induced diuresis and natriuresis. 5. These data indicate that the in vivo renal vasodilator action of adrenomedullin is mediated by the release of NO. The glibenclamide-sensitive potassium channel is not involved in the renal action of adrenomedullin, at least, not in anaesthetized dogs. Since the inhibition of L-NOARG of adrenomedullin-induced diuresis occurred concomitantly with the attenuation of the renal vasodilator action of adrenomedullin, direct involvement of NO in adrenomedullin-induced diuresis remains to be established.
Miura
K
K
Department of Pharmacology, Osaka City University Medical School, Japan.
Ebara
T
T
Okumura
M
M
Matsuura
T
T
Kim
S
S
Yukimura
T
T
Iwao
H
H
D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D014664:Vasodilation
D000959:Antihypertensive Agents; D010455:Peptides; D015221:Potassium Channels; D053607:Adrenomedullin; D009569:Nitric Oxide; D001120:Arginine; D005905:Glyburide