α-Calcitonin gene-related peptide (α-CGRP) is a regulatory neuropeptide of 37 amino acids. It is widely distributed in the central and peripheral nervous system, predominantly in cell bodies of the dorsal root ganglion (DRG). It is the most potent vasodilator known to date and has inotropic and chronotropic effects. Using pharmacological and genetic approaches, our laboratory and other research groups established the protective role of α-CGRP in various cardiovascular diseases such as heart failure, experimental hypertension, myocardial infarction, and myocardial ischemia/reperfusion injury (I/R injury). α-CGRP acts as a depressor to attenuate the rise in blood pressure in three different models of experimental hypertension: (1) DOC-salt, (2) subtotal nephrectomy-salt, and (3) L-NAME-induced hypertension during pregnancy. Subcutaneous administration of α-CGRP lowers the blood pressure in hypertensive and normotensive humans and rodents. Recent studies also demonstrated that an α-CGRP analog, acylated α-CGRP, with extended half-life (~7 h) reduces blood pressure in Ang-II-induced hypertensive mouse, and protects against abdominal aortic constriction (AAC)-induced heart failure. Together, these studies suggest that α-CGRP, native or a modified form, may be a potential therapeutic agent to treat patients suffering from cardiac diseases.
Keywords: calcitonin gene-related peptide (CGRP); cardiovascular diseases; heart failure; hypertension; myocardial infarction; neuropeptide.