ROLE OF ANGIOTENSIN-II AND BRADYKININ ON AORTIC COLLAGEN FOLLOWING CONVERTING-ENZYME INHIBITION IN SPONTANEOUSLY HYPERTENSIVE RATS

We previously showed that chronic angiotensin-converting enzyme (ACE) inhibition prevented the increase in aortic collagen in spontaneously hypertensive rats (SHRs) independently of blood pressure reduction. Th e aim of the present study was to determine whether the effects of ACE inhibition on aortic fibrosis were due to inhibition of angiotensin I I formation, preservation of bradykinin, or a combination of both. Fou r week-old SHRs were treated for 4 months with the ACE inhibitor quina pril, quinapril with the bradykinin B-2 receptor antagonist Hoe 140, o r the angiotensin II AT(1) receptor antagonist CI996. Control SHR and Wistar-Kyoto (WKY) rats received a placebo for the same period of time . At the end of the treatment, as compared to conscious SHR and WKY co ntrols, quinapril completely prevented the development of hypertension , whereas quinapril-Hoe 140 and the AT(1) receptor antagonist produced only a partial reduction of blood pressure. In relation with blood pr essure changes, aortic hypertrophy was significantly prevented by quin april but not by quinapril-Hoe 140 or CI996. In contrast, aortic colla gen accumulation was completely prevented by all three treatments. The study provides evidence that in young live SHRs, the prevention of ao rtic collagen accumulation is independent of blood pressure changes an d bradykinin preservation and involves exclusively angiotensin II inhi bition through AT(1) receptors.