Renal vascular and tubular actions of calcitonin gene-related peptide: effect of NG-nitro-L-arginine methyl ester.
The existence of calcitonin gene-related peptide (CGRP) nerve fibers and CGRP receptors in the kidney and the coupling of the receptors to adenylyl cyclase suggest that CGRP participates in renal regulation. This study investigates the dose-effect relationship of CGRP on renal blood flow (RBF) and arterial conductance, glomerular filtration rate (GFR) and tubular excretion in Inactin-anesthetized, Sprague-Dawley rats. The contributions of endothelium-derived relaxing factor/nitric oxide in the renal actions of CGRP also were investigated via renal arterial injection of the nitric oxide synthase inhibitor, NG-nitro-L-arginine 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 heart rate. Low doses of CGRP increased RBF, arterial conductance and GFR, 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 lowest dose of CGRP was attenuated by the low dose and abolished by the high dose of L-NAME. L-NAME did not inhibit the diuretic, natriuretic and kaliuretic effects elicited by high doses of CGRP. The results show that a low dose of CGRP causes renal vasodilatation via the release of endothelium-derived relaxing factor/nitric acid.
Elhawary
A M
AM
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Pang
C C
CC
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*
D010656:Phenylephrine; D009569:Nitric Oxide; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester