Attenuation of adrenomedullin‐induced renal vasodilatation by N^G‐nitro L‐arginine but not glibenclamide

Abstract

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' min-) 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 N0-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.

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…The peptide has been demonstrated in the endothelial cells of human cavernosal tissue (Marinoni et al, 2005). Adrenomedullin inhibits the contraction of several types of smooth muscle cells not only through an increase in cAMP production, but also be stimulating the release of NO (Miura et al, 1995). Injected intracavernosally in cats, adrenomedullin caused increases in intracavernosal pressure and in penile length, an effect also found with CGRP (Champion et al, 1997a,b,c).…”

Hemodynamic, Hormone, and Urinary Effects of Adrenomedullin Infusion in Essential Hypertension

“…26 Although the exact mechanisms by which AM produces vasodilatation are not defined, there is evidence that it acts indirectly through NO and through cAMP-mediated mechanisms and via the inhibition of angiotensin II and endothelin production. 20,[32][33][34] AM in animals also acts in the kidney, relaxing both efferent and afferent glomerular arterioles, increasing glomerular filtration, and inducing natriuresis. 32,33 In addition, AM may inhibit VSMC and cardiac muscle hypertrophy.…”

Renoprotective Effect of Chronic Adrenomedullin Infusion in Dahl Salt-Sensitive Rats

“…Interestingly, long-term AM infusion significantly decreased the plasma renin concentration in DS rats. In previous studies, the effects of acute administration of AM on plasma renin activity in vivo were controversial, 20,21 because excessive reduction of blood pressure induced by AM may induce renin secretion. However, Khan et al 17 reported that chronic administration of AM significantly reduced the plasma renin activity in renovascular hypertensive rats, suggesting direct inhibitory effects of chronic AM infusion on renin secretion.…”