RENAL VASCULAR AND TUBULAR ACTIONS OF CALCITONIN-GENE-RELATED PEPTIDE- EFFECT OF N-G-NITRO-L-ARGININE METHYL-ESTER

The existence of calcitonin gene-related peptide (CGRP) nerve fibers a nd CGRP receptors in the kidney and the coupling of the receptors to a denylyl cyclase suggest that CGRP participates in renal regulation. Th is study investigates the dose-effect relationship of CGRP on renal bl ood flow (RBF) and arterial conductance, glomerular filtration rate (G FR) and tubular excretion in Inactin-anesthetized, Sprague-Dawley rats . The contributions of endothelium-derived relaxing factor/nitric oxid e in the renal actions of CGRP also were investigated via renal arteri al injection of the nitric oxide synthase inhibitor, N-G-nitro-L-argin ine methyl ester (L-NAME, 0.5 or 5 mg/kg). Renal arterial infusion of CGRP (0.3-300 pmol/kg/min) did not affect mean arterial pressure or he art rate. Low doses of CGRP increased RBF, arterial conductance and GF R, but the highest dose reduced RBF and conductance without affecting GFR. High doses of CGRP also increased urine flow and excretions of Na + and K+. The renal vasodilator but not the constrictor effect of CGRP was inhibited by both doses of L-NAME. The increase in GFR by the low est dose of CGRP was attenuated by the low dose and abolished by the h igh dose of L-NAME. L-NAME did not inhibit the diuretic, natriuretic a nd kaliuretic effects elicited by high doses of CGRP. The results show that a low dose of CGRP causes renal vasodilatation via the release o f endothelium-derived relaxing factor/nitric acid.