Mouse aorta: a preparation highly sensitive to the vasodilatory action of CGRP

Calcitonin gene-related peptide (CGRP), carbamylcholine, and vasoactive intestinal peptide (VIP) caused a concentration-related relaxation in mouse aorta precontracted to noradrenaline. Maximal relaxations obtained 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 exclusively mediated by endothelial cell-derived factors, whereas CGRP maintained a full vasodilatory action in denuded aorta. However, its concentration-response curve was slightly shifted to the right in the absence of endothelium. The relaxation caused by CGRP was also slightly inhibited at 2 x 10(-8) M by removal of endothelium and in the presence of methylene blue, NG-nitro-L-arginine methylester (L-NAME), or glibenclamide but was not affected by atropine, propranolol, indomethacin, or tetrodotoxin. Moreover, the absence of Ca2+ in the bathing solution had no inhibitory effect on CGRP-induced relaxation in noradrenaline-precontracted aorta. It is concluded that the relaxation evoked by CGRP in the mouse aorta does not mainly depend on an endothelium-derived factor or on the activation of ATP-sensitive K+ (KATP) channels but rather is caused by a mechanism primarily associated with the inhibition of the mobilization of intracellular Ca2+.