Amylin-induced relaxation of the perfused mesenteric arterial bed: meditation by calcitonin gene-related peptide receptors.

ABSTRACT

Amylin is a 37-amino acid peptide that shares considerable homology with calcitonin gene-related peptide (CGRP). Both peptides exert glycoregulatory actions and produce vasodilation of the cardiovascular system. We wished to determine if amylin exerts vasodilatory action in the perfused mesenteric arterial bed in a manner similar to that of CGRP and if so, to determine if amylin and CGRP share a common mechanism of action. Amylin 10(-8), 10(-7), and 10(-6)M produced significant decreases in perfusion pressure by 18, 34, and 45 mm Hg, respectively, of the perfused mesenteric arterial bed pretreated with guanethidine (7 x 10(-6)M) and precontracted with methoxamine (10(-6)-10(-5)M). Amylin was approximately 10 times less potent than CGRP. This vasodilatory effect was not antagonized by atropine in a concentration (10(-6)M) that blocked the vasodilatory action of acetylcholine (ACh) or of nadolol in a concentration that blocked the response to isoproterenol (ISO 10(-6)M). In contrast, the CGRP receptor antagonist [8-37]hCGRP blocked the response of both amylin and CGRP while failing to block the effect of ISO. The depressor effects of CGRP (10(-8)M), amylin (10(-6)M), and ISO (10(-5)M) were 38, 43, and 42 mm Hg without and 5, 12, and 44 mm Hg with [8-37]hCGRP (10(-7)M), respectively. Simultaneous administration of CGRP and amylin failed to produce an additive effect. The depressor effects of CGRP (10(-8)M), amylin (10(-7)M), and CGRP (10(-8)M) plus amylin (10(-7)M) were 50, 32, and 45 mm Hg, respectively. We conclude that amylin exerts a vasodilator action in the perfused mesenteric arterial bed by acting on CGRP1 receptors and suggest that this glycoregulatory hormone may also exert regulatory actions in the vasculature in a manner similar to that of CGRP.