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/micrograms of DNA (555) in the treated group, 2 p greater than 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), 2 p less than 10(-4]); (b) a significant decrease of intima-media wet weight [35.4 (1.0) vs. 30.9 mg (0.9), 2p less than 0.005]; and (c) without any significant effect on intima-media DNA content [96.3 (7.9) vs. 91.7 micrograms (5.7), 2p greater than 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.
Capron
L
L
Centre de Recherches sur les Maladies Vasculaires Périphériques, Association Claude Bernard, Paris, France.
Heudes
D
D
Chajara
A
A
Bruneval
P
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002404:Catheterization / Q000009:adverse effects*; D004247:DNA / Q000378:metabolism; D008297:Male; D017257:Ramipril; D051381:Rats; D011919:Rats, Inbred Strains; D013895:Thoracic Arteries / Q000293:injuries*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D004247:DNA; D017257:Ramipril