(Hypertension. 1999;33:207-211.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Angiotensin-(1–7) Reduces Smooth Muscle Growth After Vascular Injury
From The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC.
Correspondence to E. Ann Tallant, The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1032. E-mail atallant{at}wfubmc.edu
Abstract—Regulation of vascular smooth muscle cell growth is critical to the maintenance of normal blood flow and vessel patency. Angiotensin-(1–7) [Ang-(1–7)] inhibits proliferation of vascular smooth muscle cells in vitro and opposes the mitogenic effects of angiotensin II. The present study investigated whether Ang-(1–7) inhibits vascular smooth muscle cell growth in vivo by determining its effect on neointimal formation and medial remodeling in balloon-injured carotid arteries. The carotid arteries of adult male Sprague-Dawley rats were injured with a balloon embolectomy catheter. Ang-(1–7) in saline (24 µg/kg per hour) or saline alone was infused intravenously for 12 days after injury. Pumps containing bromodeoxyuridine were implanted at the same time to determine DNA synthesis. Intravenous infusion increased plasma Ang-(1–7) to 166.0±41.2 fmol/mL (n=6) compared with 46.9±4.2 fmol/mL (n=8) in saline-infused rats. Plasma concentrations of Ang II were not changed by Ang-(1–7) infusion. Elevation in circulating Ang-(1–7) had no effect on either blood pressure or heart rate compared with saline controls. Histomorphometric analysis of carotid arteries indicated that Ang-(1–7) infusion significantly reduced neointimal area compared with rats infused with saline (0.063±0.011 versus 0.100±0.009 mm2; P<0.05). In contrast, Ang-(1–7) infusion had no effect on medial area of the injured or the contralateral uninjured artery compared with saline controls. Ang-(1–7) infusion also reduced the rate of DNA synthesis in both the neointima and the media of the injured vessels. Therefore, exogenous Ang-(1–7) inhibited vascular smooth muscle cell proliferation associated with balloon-catheter injury. Similar increases in endogenous plasma Ang-(1–7) and inhibition of neointimal growth were observed in rats after angiotensin-converting enzyme inhibitor or angiotensin type 1 receptor antagonist administration, suggesting that Ang-(1–7) may contribute to the in vivo antiproliferative effects of these agents on vascular smooth muscle.
Key Words: angiotensin • angiotensin II • muscle, smooth • vascular injury • vascular proliferation • hyperplasia
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