Human alpha- and beta-CGRP and rat alpha-CGRP are coronary vasodilators in the rat.
The effects of the recently described human alpha-calcitonin gene-related peptide (CGRP), human beta-CGRP and rat alpha-CGRP have been compared with those of the vasodilator sodium nitroprusside, on the rat and rabbit isolated heart. Hearts were perfused at constant flow and [Arg8]-vasopressin was used to increase coronary perfusion pressure. In the rat heart, the order of potency for evoking cumulative dose-dependent falls in perfusion pressure was human beta-CGRP greater than rat alpha-CGRP greater than human alpha-CGRP greater than sodium nitroprusside. In the same preparations the three CGRPs (but not sodium nitroprusside) elicited cumulative dose-related increases in heart rate. In the rabbit heart the order of potency for vasodilatation was rat alpha-CGRP greater than human alpha-CGRP greater than sodium nitroprusside. In marked contrast to results from the rat, neither rat alpha-CGRP nor human alpha-CGRP altered heart rate in the rabbit isolated heart. These results show that human alpha- and beta-CGRP and rat alpha-CGRP are vasodilators in the coronary vasculature, but that there is species variation as CGRP had a positive chronotropic effect in the rat heart but not in the rabbit heart.
D000595:Amino Acid Sequence; D000818:Animals; D015740:Calcitonin Gene-Related Peptide; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000494:pharmacology / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D051381:Rats; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents
D009419:Nerve Tissue Proteins; D014665:Vasodilator Agents; D015740:Calcitonin Gene-Related Peptide