ramipril and Hyperplasia

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.

Topics: Angioplasty, Balloon; Angiotensin-Converting Enzyme Inhibitors; Animals; Anticoagulants; Aorta, Thoracic; Drug Synergism; Drug Therapy, Combination; Heparin; Hyperplasia; Male; Ramipril; Rats; Rats, Wistar; Time Factors; Tunica Intima

Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce the intimal proliferation in animal models of arterial angioplasty and vein bypass grafting. This study examines the effect of high-dose ramipril, an ACE inhibitor that does not contain a sulfhydryl group, on the development of intimal hyperplasia in experimental vein bypass grafts. Twenty New Zealand White rabbits underwent common carotid interposition bypass grafting. Twelve were treated with ramipril (2 mg/kg/day; po) five days prior to surgery and thereafter until harvest. The remaining 8 animals were used as controls. Vein grafts were harvested at twenty-eight days by pressure fixation (80 mmHg). The grafts were sectioned into proximal, middle, and distal thirds, and the thickness of the intima and the media and the area of the lumen from each segment were determined by videomorphometry. The effect of ramipril on the [H3]thymidine incorporation into DNA of serum-stimulated smooth muscle cells (culture passage 6 to 12) was also assessed. There was a 50% mortality rate in the rabbits that received ramipril, and this was assumed to be related to the high dose of the drug. Ramipril treatment reduced mean vein graft intimal area by 34% (P > 0.05), but this was accompanied by an increase of 73% in the mean medial area of the vein grafts as compared with controls. These changes resulted in a decrease in the mean intimal ratio (intima/[intima + media]) by 39% in the ramipril group as compared with controls. Ramipril did not inhibit [H3]thymidine incorporation into DNA of serum-stimulated smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Culture Techniques; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Graft Occlusion, Vascular; Hyperplasia; Jugular Veins; Male; Muscle, Smooth, Vascular; Rabbits; Ramipril; Random Allocation; Thymidine; Tunica Intima; Tunica Media