Functional role of alpha-calcitonin gene-related peptide in the regulationof the cardiovascular system

It remains unknown whether the extent of vasoactive response to exogenous c alcitonin gene-related peptide (CGRP) varies among different regional vascu lar beds. It is also unclear whether endogenous CGRP plays a functional rol e in regulating basal vascular activity. To address these two issues, exper iments were conducted in 27 anesthetized rats instrumented with a carotid f low probe and catheters in a jugular vein, left ventricle (LV), and femoral artery, and in 6 conscious dogs, chronically instrumented with LV pressure gauge, aortic and atrial catheters, and ascending aortic, coronary, caroti d, and renal flow probes. In both species, administration of human alpha -C GRP (0.1-0.5 mug/kg, i.v.) induced a dose-dependent peripheral vasodilation that was completely abolished by pretreatment with alpha -CGRP[8-37] (30 m ug/kg/min, i.v.), a competitive antagonist of CGRP receptors. Regional bloo d flow measured by the radioactive microsphere technique in rats showed tha t the a-CGRP (0.3 mug/kg, i.v.)-induced increase in blood flow was greater (p<0.05) in the heart (+53<plus/minus>16%) than in the brain (+14 +/-6%). I n the presence of beta -adrenergic receptor blockade with propranolol, howe ver, the increases in blood flow in these two vascular beds were identical. In conscious dogs, alpha -CGRP (0.3 mug/kg, i.v.) produced similar increas es in coronary (+24 +/-6%), carotid (+26 +/-3%), and renal (+26 +/-6%) bloo d flow, which were different from the patterns induced by other vasodilator s; at an equivalent level of reduction in mean arterial pressure and total peripheral resistance, a-CGRP increased coronary and carotid blood flow sig nificantly less (p < 0.05) than adenosine or nitroprusside. Unlike <alpha>- CGRP, adenosine and nitroprusside, as expected, induced pronounced differen tial blood flow changes in these vascular beds. Neither systemic hemodynami cs nor regional blood flow distribution was altered by the administration o f a pharmacological blocking dose of alpha -CGRP[8-37] in the two species. Thus, we conclude that endogenous alpha -CGRP does not play an important ro le in cardiovascular regulation under normal, resting conditions, although exogenous alpha -CGRP induces a marked, comparable vasorelaxation in differ ent regional vascular beds.