Mechanism of CGRP-induced vasodilation in the rat isolated perfused kidney

We investigated the intracellular mechanisms involved in calcitonin gene-related peptide (CGRP)-induced vasodilation in rat isolated perfused kidney. CGRP-1 receptor antagonist, CGRP-8-37, abolished the responses. Endothelial denudation by Triton X-100 or nitric oxide (NO) synthase inhibition by NG-nitro-L-arginine attenuated the maximum dilation by about 63 and 55%, respectively. Protein kinase A inhibitor, KT-5720, caused an about 72% inhibition in CGRP-induced maximum dilation. Soluble guanylate cyclase inhibitor, ODQ, and ATP-sensitive potassium channel blocker, glibenclamide, inhibited the CGRP-induced maximum responses by 75 and 55%, respectively. Cyclooxygenase inhibitor, indomethacin, had no effect. Our data suggest that CGRP-1 receptors, endothelium, NO synthase, protein kinase A, soluble guanylate cyclase, and ATP-sensitive potassium channels, but not the cyclooxygenase pathway, may play a role in CGRP-induced vasodilation in rat isolated perfused kidney.