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Regional haemodynamic effects of human and rat adrenomedullin in conscious rats
Author(s) -
Gardiner S.M.,
Kemp P.A.,
March J.E.,
Bennett T.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb17179.x
Subject(s) - adrenomedullin , calcitonin gene related peptide , vasodilation , medicine , endocrinology , antagonist , hemodynamics , mesenteric arteries , calcitonin , chemistry , receptor , neuropeptide , artery
1 Male, Long Evans rats were chronically instrumented with pulsed Doppler flow probes and intravascular catheters to permit assessment of the regional haemodynamic responses to human and rat adrenomedullin, to compare the responses to human adrenomedullin to those of human α‐CGRP in the absence and presence of the CGRP 1 ‐receptor antagonist, human α‐CGRP [8–37], and to determine the involvement of nitric oxide (NO)‐mediated mechanisms in the responses to human adrenomedullin, relative to human α‐CGRP. 2 Human and rat adrenomedullin (0.3, 1, and 3 nmol kg −1 , i.v.) caused dose‐dependent hypotension and tachycardia, accompanied by increases in renal, mesenteric and hindquarters flows and vascular conductances. At the lowest dose only, the hypotensive and mesenteric vasodilator effects of rat adrenomedullin were significantly greater than those of human adrenomedullin. 3 Human α‐CGRP at a dose of 1 nmol kg −1 caused hypotension, tachycardia and increases in hindquarters flow and vascular conductance, but reductions in renal and mesenteric flows, and only transient vasodilatations in these vascular beds. These effects were substantially inhibited by human α‐CGRP [8–37] (100 nmol kg −1 min −1 ), but those of human adrenomedullin (1 nmol kg −1 ) were not; indeed, the mesenteric haemodynamic effects of the latter peptide were enhanced by the CGRP 1 ‐receptor antagonist. 4 In the presence of the NO synthase inhibitor, N G ‐nitro‐ 1 ‐arginine methyl ester ( 1 ‐NAME, 183 nmol kg −1 min −1 ), there was only a slight, but significant, inhibition of the hindquarters hyperaemic vasodilator effect of human adrenomedullin, but not that of human α‐CGRP. 5 These results indicate that the marked regional vasodilator effects of human (and rat) adrenomedullin are largely independent of NO and, in vivo , do not involve CGRP 1 ‐receptors.