Vasodilating effects of human and rat calcitonin gene-related peptides in isolated porcine coronary arteries

Abstract

Human and rat alpha-calcitonin gene-related peptides (CGRPs) caused relaxation of porcine coronary arterial strips precontracted by 10(-5) M of prostaglandin (PG) F2 alpha at low concentrations. pD2 values for human and rat CGRPs in endothelium-preserved strips were 8.41 +/- 0.03 (n = 5) and 8.49 +/- 0.03 (n = 5), respectively. The same concentrations of CGRPs relaxed the endothelium-depleted preparations. CGRPs were much more potent and had steeper concentration-response curves than isoproterenol, nitroglycerin (GTN), isobutylmethylxanthine (IBMX), verapamil and nifedipine. Like isoproterenol, GTN and IBMX, but in contrast to the calcium antagonists, the relaxing potencies of human and rat CGRPs were greatly reduced in the strips precontracted by 50 mM of KCl. The relaxation caused by human CGRP was not affected by treatment with propranolol (10(-6) M) or cimetidine (10(-5) M). Human CGRP (1.6 X 10(-8) M) caused a significant (about 2-fold) elevation of the content of cyclic AMP in coronary tissue but did not cause any change in the content of cyclic GMP. CGRP-like immunoreactive fibers were found to be localized in the adventitia but not in the media or intima of the coronary artery. These results indicate a direct and endothelium-independent potent relaxant action of CGRP in coronary vessels. This relaxation could be caused by a mechanism not shared by calcium antagonists but associated with the rise in cyclic AMP.