Cilazapril and early atherosclerotic changes after balloon injury of porcine carotid arteries

Abstract

Background. Cilazapril, a converting enzyme inhibitor, has been shown to significantly decrease the extent of intimal smooth muscle cell proliferation after arterial injury in a normotensive rat model. Methods and Results. To assess the influence of cilazapril on myofibrotic changes after balloon injury, control (n=7) or cilazapril-treated (n=9) (20 mg/kg b.i.d.) normal 3-month-old pigs underwent dilatation angioplasty of the right, and deendothelialization of the left common carotid artery. Carotid arteries isolated at 4 weeks were examined morphometrically with a computerized digitizer after in situ glutaraldehyde fixation. Both in the deendothelialized and dilated arteries, the surface area in square millimeters of the neointima and media were similar in the treated and control animals; therefore, the ratio of neointima to media was again not different. The neointimal changes included a combination of proliferative changes as well as organization of mural thrombus and were equally well distributed in the two groups of animals. At the time that the animals were killed, blood pressure (38.2±2.1 versus 56.8±4.8 mm Hg, p=0.003) and plasma angiotensin converting enzyme activity (5.6±4.1 versus 182.3±70.4, p=0.02) were lower in treated than in control pigs, but aortic media thrombogenicity (as assessed in an ex vivo perfusion flow chamber) and serum lipids were not different between groups. Conclusions. In pigs, cilazapril did not alter the development of myofibrotic changes after mild or severe balloon injury despite plasma angiotensin converting enzyme activity inhibition.