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(Circulation Research. 1999;85:1199.)
© 1999 American Heart Association, Inc.

Integrative Physiology

Adrenomedullin Receptor Antagonism by Calcitonin Gene-Related Peptide(8-37) Inhibits Carotid Artery Neointimal Hyperplasia After Balloon Injury

Koichi Shimizu, Hiroyuki Tanaka, Makoto Sunamori, Fumiaki Marumo, Masayoshi Shichiri

From the Department of Cardiothoracic Surgery (K.S., H.T., M. Sunamori) and the Second Department of Internal Medicine (F.M., M. Shichiri), Tokyo Medical and Dental University, Tokyo, Japan.

Correspondence to Masayoshi Shichiri, MD, Second Department of Internal Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail mshichiri.med2{at}med.tmd.ac.jp

Abstract—Intimal injury by angioplasty results in a series of changes, including smooth muscle cell hyperplasia, that lead to vascular restenosis. Adrenomedullin, a potent vasodilator peptide, has natriuretic effects, and its plasma concentration is elevated in cardiovascular diseases. Adrenomedullin is secreted by endothelial and vascular smooth muscle cells, but its role in neointimal hyperplasia after balloon injury has not been previously described. We investigated the role of endogenous adrenomedullin in neointimal hyperplasia using an in vivo rat model of postinjury vascular restenosis. In the injured rats, bromodeoxyuridine-labeled nuclei in the media of untreated common carotid arteries were increased 2 days after injury, which were suppressed by in vivo treatment with the adrenomedullin receptor antagonist calcitonin 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 effect. The expression of adrenomedullin in the media of both untreated and treated common carotid arteries was elevated at 2 days and further enhanced in hyperplastic intima of untreated common carotid arteries at 7 days. Our findings suggest a novel role for endogenous adrenomedullin in balloon injury–induced restenosis and indicate that CGRP(8-37) may be useful for the prevention of vascular restenosis.

Key Words: balloon angioplasty • adrenomedullin • CGRP(8-37) • remodeling • neointimal hyperplasia

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