Calcitonin gene-related peptide (CGRP) is a potent non-endothelium-dependent inhibitor of coronary vasomotor tone.

1 Ring segments of bovine left circumflex coronary artery were pre-contracted with 5-hydroxytryptamine or phenylephrine and then exposed to increasing concentrations of calcitonin gene-related peptide (CGRP) and other drugs. 2 CGRP administration resulted in dose-dependent inhibition of induced tone. Maximal relaxation to CGRP was 89 +/- 5% and the concentration required to achieve 50% maximal relaxation (EC50) was 2.11 +/- 1.35 X 10(-9)M. 3 CGRP-induced relaxation was not affected by removal of endothelial cells nor was it significantly altered by incubation of coronary vessels with atropine, propranolol, phentolamine (all 10(-6)M) or indomethacin (10(-5)M). 4 From these data we conclude that CGRP is a potent inhibitor of coronary artery vasomotor tone which appears to act directly on vascular smooth muscle rather than through the release of a secondary mediator. These data support the possibility that CGRP may play a role in non-adrenergic, non-cholinergic regulation of coronary artery tone.