Antagonistic effect of human alpha-CGRP [8-37] on the in vivo regional haemodynamic actions of human alpha-CGRP.
In conscious rats, infusion of human alpha-CGRP [8-37] (30 nmol/kg/min) caused small, reversible reductions in hindquarters flow and vascular conductance only, whereas at a dose of 300 nmol/kg/min there was a tachycardia and an increase in mean arterial blood pressure, together with renal, mesenteric and hindquarters vasoconstrictions. Human alpha-CGRP (0.03 nmol/kg/min) caused tachycardia, hypotension, and transient renal, but sustained hindquarters, vasodilatation; these changes were accompanied by mesenteric vasoconstriction. Infusion of human alpha-CGRP [8-37] (30 nmol/kg/min) during administration of human alpha-CGRP (0.03 nmol/kg/min) abolished the effects of the latter but these re-appeared when the human alpha-CGRP [8-37] infusion was stopped. This dose of human alpha-CGRP [8-37] did not affect cardiovascular responses to isoprenaline. These results indicate that human alpha-CGRP [8-37] is an effective antagonist of the cardiovascular actions of human alpha-CGRP in vivo.
Gardiner
S M
SM
Department of Physiology and Pharmacology, Queen's Medical Centre, Nottingham, U.K.
Compton
A M
AM
Kemp
P A
PA
Bennett
T
T
Bose
C
C
Foulkes
R
R
Hughes
B
B
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide; D007545:Isoproterenol