ANGIOTENSIN-CONVERTING ENZYME-INHIBITION PREVENTS THE INCREASE IN AORTIC COLLAGEN IN RATS

Four groups of 4-week-old spontaneously hypertensive rats were treated during 4 months with the angiotensin converting enzyme inhibitor quinapril at 1 mg/kg per day (Q1) or 10 mg/kg per day (Q10), hydralazine at 15 mg/kg per day (H), or placebo (P). In the first set of experiments, blood pressure was measured in conscious rats, and plasma and aortic angiotensin converting enzyme activities were evaluated. In the second set of experiments, histomorphometric parameters of the thoracic aorta were evaluated. Mean blood pressure was lower in the Q10 and H groups (136+/-16 and 149+/-11 mm Hg) compared with the P group (190+/-23 mm Hg) (P<.01). The Q1 group showed mean blood pressure values (171+/-15 mm Hg) lower than the P group (P<.05) but significantly higher than the Q10 and H groups (P<.01 and P<.05, respectively). Aortic medial cross-sectional area was significantly lower in the H and Q10 groups (455+/-61 and 487+/-57 x 10(3) mu m(2)) than in the P group (636+/-72 x 10(3) mu m(2)) (P<.001). In the Q1 group, medial cross-sectional area was lower(550+/-65 x10(3) mu m(2)) than the P group (P<.01) but higher than the Q10 and H groups. In the Q10 and Q1 groups, the collagen content of the aortic media was significantly lower than in the two other groups (P<.01) (Q1, 15.3+/-4.6; Q10, 14.3+/-4.0; H, 18.6+/-5.0; P, 21.9+/-4.7x10(3) mu m(2)/mm of aorta). Aortic angiotensin converting enzyme activity was inhibited by approximately 60% in both groups treated with quinapril, whereas plasma angiotension converting enzyme activity was reduced only in the Q10 rats. These results show that, whereas both hydralazine and quinapril prevented the development of aortic hypertrophy in a pressure-dependent manner, the prevention of the increase in aortic collagen was observed only after quinapril treatment. This latter effect of angiotensin converting enzyme inhibition was not related to the blood pressure reduction but was associated with the reduction of aortic and not plasma converting enzyme.