Angiotensin-(1-7) reduces smooth muscle growth after vascular injury

Regulation of vascular smooth muscle cell growth is critical to the mainten ance of normal blood flow and vessel patency. Angiotensin-(1-7) [Ang-(1-7)] inhibits proliferation of vascular smooth muscle cells in vitro and oppose s the mitogenic effects of angiotensin II. The present study investigated w hether Ang-(1-7) inhibits vascular smooth muscle cell growth in vivo by det ermining its effect on neointimal formation and medial remodeling in balloo n-injured carotid arteries. The carotid arteries of adult male Sprague-Dawl ey rats were injured with a balloon embolectomy catheter. Ang-(1-7) in sali ne (24 mu g/kg per hour) or saline alone was infused intravenously for 12 d ays 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 chang ed 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. Histo morphometric analysis of carotid arteries indicated that Ang-(1-7) infusion significantly reduced neointimal area compared with rats infused with sali ne (0.063+/-0.011 versus 0.100+/-0.009 mm(2); P<0.05). In contrast, Ang-(1- 7) infusion had no effect on medial area of the injured or the contralatera l uninjured artery compared with saline controls. Ang-(1-7) infusion also r educed 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 growt h were observed in rats after angiotensin-converting enzyme inhibitor or an giotensin 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.