Comparison of responses to rat and human adrenomedullin in the hindlimb vascular bed of the cat.
Responses to rat (r) adrenomedullin (ADM) and human (h) ADM were compared in the hindlimb vascular bed of the cat under conditions of controlled blood flow. Intra-arterial injections of rADM and hADM in doses of 0.03-1 nmol caused dose-related decreases in hindlimb perfusion pressure. In terms of relative vasodilator activity, rADM was similar to hADM. The time course of the vasodilator response and the recovery half times (T1/2) for the vasodilator response to rADM and hADM were not significantly different. Decreases in hindlimb perfusion pressure in response to rADM and hADM were not altered by the calcitonin gene-related peptide receptor antagonist, rCGRP(8-37), at the same time, vasodilator responses to calcitonin gene-related peptide (CGRP) were significantly reduced. The T1/2 of the vasodilator response to rADM and hADM were significantly greater after administration of the cAMP-selective, type IV phosphodiesterase inhibitor, rolipram. These data demonstrate that decreases in hindlimb perfusion pressure in response to rADM and hADM are similar and that vasodilator responses to rADM are not dependent on the activation of CGRP receptors in the hindlimb vascular bed of the cat. These data further suggest that decreases in hindlimb perfusion pressure in response to rADM are mediated by smooth muscle increases in cAMP levels.
Champion
H C
HC
Department of Pharmacology and Medicine SL83, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Lambert
D G
DG
McWilliams
S M
SM
Shah
M K
MK
Murphy
W A
WA
Coy
D H
DH
Kadowitz
P J
PJ
D053607:Adrenomedullin; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000494:pharmacology; D002415:Cats; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000502:physiology; D020889:Rolipram; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D010446:Peptide Fragments; D010455:Peptides; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D018015:Receptors, Calcitonin Gene-Related Peptide; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide; D020889:Rolipram