ATTENUATION OF ADRENOMEDULLIN-INDUCED RENAL VASODILATATION BY N-G-NITRO-L-ARGININE BUT NOT GLIBENCLAMIDE

1 The present study was conducted in order to elucidate the in vivo co ntribution of nitric oxide (NO) and the glibenclamide-sensitive potass ium channel in the renal action of adrenomedullin in anaesthetized dog s. 2 Intrarenal arterial infusion of adrenomedullin (20 ng kg(-1) min( -1)) elicited a pronounced increase in renal blood flow with no change s in systemic blood pressure. The renal vasodilator action of adrenome dullin was markedly attenuated by pretreatment with N-G-nitro L-argini ne (L-NOARG), but this was reversed by continuous infusion of L-argini ne. 3 Pretreatment with glibenclamide almost completely blocked the re nal vasodilatation induced by lemakalim, but had no effect on the rena l vasodilator and diuretic action of adrenomedullin. 4 Intrarenal arte rial infusion of adrenomedullin induced diuresis and natriuresis. Diur etic and natriuretic action of adrenomedullin was also attenuated by L -NOARG. L-Arginine partly reversed the effect of L-NOARG and adrenomed ullin-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 i nvolved in the renal action of adrenomedullin, at least, not in anaest hetized dogs. Since the inhibition of L-NOARG of adrenomedullin-induce d diuresis occurred concomitantly with the attenuation of the renal va sodilator action of adrenomedullin, direct involvement of NO in adreno medullin-induced diuresis remains to be established.