Synergistic inhibitory effect of angiotensin-converting enzyme inhibitor and heparin on intimal hyperplasia after rat aorta injury.

The respective efficacies of angiotensin-converting enzyme (ACE) inhibitor and standard heparin were investigated with respect to their inhibitory effects on intimal hyperplasia after balloon denudation of rat aorta. Local angiotensin II effects in the artery wall may participate in regulation of the vascular response to arterial injury, apparently independent of the plasma renin and angiotensin system. ACE inhibitors have been shown to block intimal hyperplasia after arterial injury in rats. Increasing evidence points toward an inhibitory effect of heparin on intimal hyperplasia independent of anticoagulation. Balloon catheter aortic denudation was performed in 25 rats pharmacologically treated from six days or one day before to fourteen days after surgery and split into four groups: group A (control group), normal feeding; group B (ramipril group), ramipril 10 mg/kg/day orally; group C (heparin group), heparin 1200 IU/kg/day subcutaneously; group D (combined group), both ramipril and heparin. Animals were killed and aortas were perfused and fixed at physiologic pressure fourteen days after denudation. Cross-sectional intima-to-media area ratios (I-M ratio) were calculated by an image analyze system.