CALCITONIN-GENE-RELATED PEPTIDE REDUCES RENAL VASCULAR-RESISTANCE ANDMODULATES ET-1-INDUCED VASOCONSTRICTION

Calcitonin gene-related peptide (CGRP) is a novel polypeptide that exe rts important effect on the cardiovascular system through its vasorela xant properties. We studied in vivo in normal rats the effect of acute administration of CGRP on whole kidney function and showed that the i ntravenous infusion of the peptide resulted in a fall of blood pressur e associated with a marked increase in renal plasma flow (RPF) as well as glomerular filtration rate (GFR). These changes were reversible wi th discontinuation of CGRP infusion. To evaluate whether the renal hem odynamic responses to the peptide were mediated by endogenous vasodila tory prostaglandins of endothelial origin, animals were preexposed to indomethacin, a cyclooxygenase enzyme inhibitor. Inhibition of prostag landins synthesis with indomethacin failed, however, to prevent the in crease in RPF and GFR observed during CGRP infusion. By contrast, N-G- nitro-L-arginine methyl ester (L-NAME), which inhibits the synthesis o f 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 rena l 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-l. Thi s indicates that CGRP regulates renal hemodynamics and modulates the d eleterious effects of vasoconstrictive substances on the kidney.