EFFECTS OF CALCITONIN-GENE-RELATED PEPTIDE RECEPTOR ANTAGONISTS ON RENAL ACTIONS OF ADRENOMEDULLIN

1 Adrenomedullin is a novel vasoactive peptide which is produced in th e lungs, ventricle, kidneys, heart and adrenal medulla. Adrenomedullin shows homology to calcitonin gene-related peptide (CGRP) and has simi lar pharmacological actions to CGRP. 2 This study examined the dose-re sponse effects of adrenomedullin (rat, 11-50) on mean arterial pressur e (MAP), heart rate (HR), renal blood how (RBF), glomerular filtration rate (GFR) and renal tubular electrolyte excretion in Inactin-anaesth etized Sprague Dawley rats. The possible involvement of CGRP receptors in actions of adrenomedullin was also examined via renal arterial inj ection of a CGRP receptor antagonist, CGRP (8-37) (1 or 10 nmol kg(-1) ) or [Tyr(0)]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 rena l K+ excretion but dose-dependently increased PBF and arterial conduct ance, GFR, urine flow and Na+ excretion. 4 The renal actions of adreno medullin were not blocked by either the low or the high dose of CGRP(8 -37) or [Tyr(0)]CGRP(28-37). 5 The results show that adrenomedullin ca uses renal vasodilatation, increments in GFR, diuresis and natriuresis . The renal actions of adrenomedullin are not mediated via the activat ion of CGRP(1) receptors.