Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: Roles of the peripheral vasopressin and central cholinergic systems

Abstract

Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g) female rats (N = 7 in each group) the effects of intracerebroventricularly (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral V-1 receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1) icv ADM (750 ng/10 mu L) caused an increase in both blood pressure and HR (Delta MAP = 11.8 +/- 2.3 mmHg and Delta HR = 39.7 +/- 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP(8-37)) and ADM receptor antagonist (ADM(22-52)) blocked the effect of central ADM on blood pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 mu g/10 mu L, icv) and the muscarinic receptor antagonist atropine (5 mu g/10 mu L, icv) prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 mu g/10 mu L, icv). 4) The V-1 receptor antagonist [beta-mercapto-beta-beta-cyclopentamethylenepropionyl(1), O-me-Tyr(2),Arg(8)]-vasopressin (V2255; 10 mu g/kg), that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V-1 receptors in the increasing effects of icv ADM on blood pressure and HR.