EFFECT OF RAMIPRIL, AN INHIBITOR OF ANGIOTENSIN CONVERTING ENZYME, ON THE RESPONSE OF RAT THORACIC AORTA TO INJURY WITH A BALLOON CATHETER

We have studied the effect of ramipril (10 mg/kg daily by gastric gavage) on the development of neointima 2 and 14 days after injury to rat aorta with a balloon catheter. In treated animals, there was no significant inhibition of the early mitotic reaction after injury (synthesis of DNA, as reflected by aortic thymidine incorporation on the second day): the mean (95% confidence interval) was 3,553 (892) in the control group vs. 2,853 disintegrations/min/mu-g of DNA (555) in the treated group, 2p > 0.15. However, ramipril decreased the amount of neointima formed 14 days after injury, as characterized by (a) a highly significant decrease of the intima to intima + media areas ratio [21.1 (2.4) vs. 13.7% (2.2), 2p < 10(-4)]; (b) a significant decrease of intima-media wet weight [35.4 (1.0) vs. 30.9 mg (0.9), 2p < 0.005]; and (c) without any significant effect on intima-media DNA content [96.3 (7.9) vs. 91.7-mu-g (5.7), 2p > 0.3]. These observations suggest that angiotensin converting enzyme inhibitors may not act mainly through an inhibition of smooth muscle cell proliferation. Other effects, such as inhibition of migration, hypertrophy, and matrix synthesis, should also be considered.