Effects of calcitonin gene‐related peptide receptor antagonists on renal actions of adrenomedullin

Abstract

Adrenomedullin is a novel vasoactive peptide which is produced in the lungs, ventricle, kidneys, heart and adrenal medulla. Adrenomedullin shows homology to calcitonin gene‐related peptide (CGRP) and has similar pharmacological actions to CGRP. This study examined the dose‐response effects of adrenomedullin (rat, 11–50) on mean arterial pressure (MAP), heart rate (HR), renal blood flow (RBF), glomerular filtration rate (GFR) and renal tubular electrolyte excretion in Inactin‐anaesthetized Sprague Dawley rats. The possible involvement of CGRP receptors in actions of adrenomedullin was also examined via renal arterial injection of a CGRP receptor antagonist, CGRP (8–37) (1 or 10 nmol kg−1) or [Tyr0]CGRP(28–37) (3 or 30 nmol kg−1), starting 15 min prior to the administration of adrenomedullin. Renal arterial infusion (0.001 to 1 nmol kg−1) of adrenomedullin did not alter MAP, HR and renal K+ excretion but dose‐dependently increased RBF and arterial conductance, GFR, urine flow and Na+ excretion. The renal actions of adrenomedullin were not blocked by either the low or the high dose of CGRP(8–37) or [Tyr0]CGRP(28–37). The results show that adrenomedullin causes renal vasodilatation, increments in GFR, diuresis and natriuresis. The renal actions of adrenomedullin are not mediated via the activation of CGRP1 receptors. 1995 British Pharmacological Society