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Human alpha- and beta-CGRP and rat alpha-CGRP are coronary vasodilators in the rat
Insights
Human and rat calcitonin gene-related peptides (CGRP) act as vasodilators in isolated rat and rabbit hearts. However, CGRP demonstrated species-specific effects on heart rate, increasing it in rats but not rabbits.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Endocrinology
Background:
- Calcitonin gene-related peptide (CGRP) is a newly identified peptide with known vasodilatory properties.
- Understanding the specific effects of different CGRP variants across species is crucial for cardiovascular research.
Purpose of the Study:
- To compare the vasodilatory potency of human alpha-CGRP, human beta-CGRP, and rat alpha-CGRP against sodium nitroprusside.
- To investigate the effects of these CGRP variants on heart rate in isolated rat and rabbit hearts.
Main Methods:
- Isolated rat and rabbit hearts were perfused at a constant flow.
- Vasodilatory responses were measured by changes in coronary perfusion pressure.
- [Arg8]-vasopressin was used to induce vasoconstriction for testing vasodilator efficacy.
- Heart rate chronotropic effects were also monitored.
Main Results:
- In rat hearts, human beta-CGRP was the most potent vasodilator, followed by rat alpha-CGRP, human alpha-CGRP, and sodium nitroprusside.
- Human alpha-CGRP, human beta-CGRP, and rat alpha-CGRP increased heart rate in rat preparations.
- In rabbit hearts, rat alpha-CGRP was the most potent vasodilator, followed by human alpha-CGRP and sodium nitroprusside.
- Neither human nor rat alpha-CGRP affected heart rate in rabbit hearts.
Conclusions:
- Human alpha-CGRP, human beta-CGRP, and rat alpha-CGRP are effective vasodilators in coronary vasculature.
- Significant species variation exists in the cardiovascular effects of CGRP, particularly concerning its chronotropic impact on the heart.
Abstract:
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.