Effects of calcitonin gene-related peptide receptor antagonists on renal actions of adrenomedullin.
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.
Elhawary
A M
AM
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Poon
J
J
Pang
C C
CC
D053607:Adrenomedullin; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004231:Diuresis / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009994:Osmolar Concentration; D010455:Peptides / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010455:Peptides; D053607:Adrenomedullin; D012964:Sodium; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium