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+.
Pomerleau
F
F
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
Fournier
A
A
Cadieux
A
A
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D014660:Vasoactive Intestinal Peptide; D015740:Calcitonin Gene-Related Peptide