Calcitonin gene-related peptide reduces renal vascular resistance and modulates ET-1-induced vasoconstriction.
Calcitonin gene-related peptide (CGRP) is a novel polypeptide that exerts important effect on the cardiovascular system through its vasorelaxant properties. We studied in vivo in normal rats the effect of acute administration of CGRP on whole kidney function and showed that the intravenous infusion of the peptide resulted in a fall of blood pressure associated with a marked increase in renal plasma flow (RPF) as well as glomerular filtration rate (GFR). These changes were reversible with discontinuation of CGRP infusion. To evaluate whether the renal hemodynamic responses to the peptide were mediated by endogenous vasodilatory prostaglandins of endothelial origin, animals were preexposed to indomethacin, a cyclooxygenase enzyme inhibitor. Inhibition of prostaglandins synthesis with indomethacin failed, however, to prevent the increase in RPF and GFR observed during CGRP infusion. By contrast, NG-nitro-L-arginine methyl ester (L-NAME), which inhibits the synthesis of nitric oxide, a newly discovered endothelium-derived relaxing factor, completely abolished the renal hemodynamic changes induced by CGRP. Moreover, L-arginine infusion in L-NAME-treated rats restored the renal response to CGRP. We have also shown that systemic infusion of CGRP progressively normalized RPF and GFR that were reduced in response to a bolus intravenous injection of the vasoconstrictor endothelin-1. This indicates that CGRP regulates renal hemodynamics and modulates the deleterious effects of vasoconstrictive substances on the kidney.
Amuchastegui
C S
CS
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Remuzzi
G
G
Perico
N
N
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D016232:Endothelins; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin