CENTRALLY INDUCED VASOPRESSOR AND SYMPATHETIC RESPONSES TO A NOVEL ENDOGENOUS PEPTIDE, ADRENOMEDULLIN, IN ANESTHETIZED RATS

Possible central actions of adrenomedullin were explored and compared with the peripheral effects by injecting it into the lateral ventricle , cisterna magna, and femoral vein in urethane-anesthetized rats. Adre nomedullin, 1.0 to 3.0 nmol/kg, injected intravenously (IV), caused a transient vasodepression of about 10 to 30 mm Hg, dose dependently, wh ich lasted for <15 min. On the other hand, intracerebroventricular (IC V) and intracisternal (IC) injections of adrenomedullin elicited susta ined elevations of arterial pressure of gradual onset, dose dependentl y; the arterial pressure started to rise at about 3 min after the inje ction, and gained peak response after >20 min. The pressor response la sted for >2 h. Heart rate was not significantly influenced by these do ses of adrenomedullin. The abdominal sympathetic outflow was markedly increased in relation to the blood pressure elevation. The time-course of the responses was quite similar with both ICV and IC injections. H ypotensive effects of IV injected adrenomedullin was partially attenua ted, and the centrally induced vasopressor responses were abolished by the pretreatment with human calcitonin gene-related peptide (hCGRP)-r eceptor antagonist, hCGRP(8-37). These findings indicate that the rece ptors for adrenomedullin exist in the brain, and that the receptor sit e may be anatomically far from the surface of the brain and the ventri cular system because the onset of the pressor response was delayed. Or , CGRP and adrenomedullin may share the same receptors, particularly i n the brain.