Analysis of responses to hAmylin, hCGRP, and hADM in isolated resistance arteries from the mesenteric vascular bed of the rat

Responses to human calcitonin gene-related peptide (hCGRP) and human adreno medullin (hADM) hAmylin were investigated in isolated mesenteric resistance arteries from the rat. The results of the present investigation show that hCGRP, hAmylin, and hADM induce dose-related vasodilator responses in isola ted resistance arteries from the rat mesenteric vascular bed. Vasodilator r esponses to hCGRP and hAmylin were not altered after denuding the vascular endothelium, after administration of the nitric oxide synthase inhibitor L- NA, or after administration of the soluble guanylate cyclase inhibitor ODQ, suggesting that vasodilator responses to hCGRP and hAmylin are not mediate d by the release of nitric oxide from the vascular endothelium and the subs equent increase in cGMP. Vasodilator responses to hCGRP, hAmylin, and hADM were not altered by the vascular selective K-ATP(+) channel antagonist U-37 883A. The role of the CGRP(1) receptor was investigated and responses to hC GRP and hAmylin, but not hADM, were significantly reduced following adminis tration of hCGRP-(8-37). Moreover, vasodilator responses to hCGRP and hAmyl in, but not hADM, were significantly reduced by hAmylin-(8-37), suggesting that an hAmylin-(8-37)-sensitive receptor mediates responses to hCGRP and h Amylin in the rat mesenteric artery. These data suggest that hCGRP and hAmy lin have direct vasodilator effects in the isolated mesenteric resistance a rtery that are mediated by hAmylin-(8-37)- and hCGRP-(8-37)-sensitive recep tors. (C) 2001 Elsevier Science Inc. All rights reserved.