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

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Abstract
1 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. 2 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. 3 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. 4 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). 5 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.