ACE-inhibition promotes apoptosis after balloon injury of rat carotid arteries

Objective: Angiotensin II stimulates vascular smooth muscle cell (VSMC) gro wth, and is considered to be an important mediator of intimal thickening af ter vascular injury. Recent evidence has indicated that VSMC apoptosis play s a major role in the response to balloon injury, and we therefore examined the effect of angiotensin converting enzyme (ACE)-inhibition on VSMC apopt osis and vascular lesion formation in the rat model of balloon injury. Meth ods: Male Sprague-Dawley rats were subjected to carotid artery balloon inju ry and randomised to a standard diet or a diet supplemented with 1 mg/ml ca ptopril in the drinking water. Animals were sacrificed 2 and 14 days after injury for assessment of apoptosis and proliferation by in situ terminal de oxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) and proliferating cell nuclear antigen (PCNA) immunohistochemistry, respect ively. At 14 days post injury, vessel cross-sections were subjected to micr oscopic morphometry and total cell numbers were determined. Results: At 2 d ays after balloon injury, captopril-beated animals displayed a significant increase in the percentage of TUNEL-positive VSMCs in the medial area (12 /- 4% vs. 1 +/- 1%; P<0.05) as compared to controls. This increase in early apoptosis was associated with decreased intimal cellularity 14 days post i njury (238 +/- 47 cells/cross-section vs. 449 +/- 75 cells/cross-section; P <0.05), and a reduction of neointimal formation (0.13 +/- 0.02 mm(2) vs. 0. 23 +/- 0.04 mm(2): P<0.05), The fraction of PCNA-positive VSMCs per cross-s ection 2 or 14 days after injury was not significantly altered by captopril administration. Conclusion: Captopril inhibits neointimal formation in the rat model of arterial injury by mechanisms involving induction of VSMC apo ptosis. (C) 2000 Elsevier Science B.V. All rights reserved.