MOUSE AORTA - A PREPARATION HIGHLY SENSITIVE TO THE VASODILATORY ACTION OF CGRP

Calcitonin gene-related peptide (CGRP), carbamylcholine, and vasoactiv e intestinal peptide (VIP) caused a concentration-related relaxation i n mouse aorta precontracted to noradrenaline. Maximal relaxations obta ined were 110, 44, and 46% with median effective concentrations (EC50) values of 7.8, 813.7, and 24.5 nM for CGRP, carbamylcholine, and VIP, respectively. The carbamylcholine- and VIP-induced relaxations were e xclusively mediated by endothelial cell-derived factors, whereas CGRP maintained a full vasodilatory action in denuded aorta. However, its c oncentration-response curve was slightly shifted to the right in the a bsence of endothelium. The relaxation caused by CGRP was also slightly inhibited at 2 x 10(-8) M by removal of endothelium and in the presen ce of methylene blue, N-G-nitro-L-arginine methylester (L-NAME), or gl ibenclamide but was not affected by atropine, propranolol, indomethaci n, or tetrodotoxin. Moreover the absence of Ca2+ in the bathing soluti on had no inhibitory effect on CGRP-induced relaxation in noradrenalin e-precontracted aorta. It is concluded that the relaxation evoked by C GRP in the mouse aorta does not mainly depend on an endothelium-derive d factor or on the activation of ATP-sensitive K+ (K-ATP) channels but rather is caused by a mechanism primarily associated with the inhibit ion of the mobilization of intracellular Ca2+.