Adrenomedullin receptor antagonism by calcitonin gene-related peptide(8-37) inhibits carotid artery neointimal hyperplasia after balloon injury

Intimal injury by angioplasty results in a series of changes, including smo oth muscle cell hyperplasia, that lead to vascular restenosis. Adrenomedull in, a potent vasodilator peptide, has natriuretic effects, and its plasma c oncentration is elevated in cardiovascular diseases. Adrenomedullin is secr eted by endothelial and vascular smooth muscle cells, but its role in neoin timal hyperplasia after balloon injury has not been previously described. W e investigated the role of endogenous adrenomedullin in neointimal hyperpla sia using an in vivo rat model of postinjury vascular restenosis. In the in jured rats, bromodeoxyuridine-labeled nuclei in the media of untreated comm on carotid arteries were increased 2 days after injury, which were suppress ed by in vivo treatment with the adrenomedullin receptor antagonist calcito nin gene-related peptide (CGRP)(8-37). Inhibition of neointimal hyperplasia by CGRP(8-37) was distinct at 7 and 14 days, whereas CGRP(1-37) had no eff ect. The expression of adrenomedullin in the media of both untreated and tr eated common carotid arteries was elevated at 2 days and further enhanced i n hyperplastic intima of untreated common carotid arteries at 7 days. Our f indings suggest a novel role for endogenous adrenomedullin in balloon injur y-induced restenosis and indicate that CGRP(8-37) may be useful for the pre vention of vascular restenosis.