ANGIOTENSIN-CONVERTING ENZYME AND MYOCARDIAL FIBROSIS IN THE RAT RECEIVING ANGIOTENSIN-II OR ALDOSTERONE

Angiotensin-converting enzyme (ACE) is present in tissues composed lar gely of fibrillar collagen such as heart valves, the adventitia of gre at vessels and intramyocardial coronary arteries, and the scar that fo llows myocardial infarction. We tested the hypothesis that such tissue ACE is related to fibrous tissue formation and that its appearance is independent of circulating renin and angiotensin peptides. For this p urpose we selected experimental models that simulate primary and secon dary hyperaldosteronism, each of which are associated with the appeara nce of myocardial fibrosis. ACE in the excised heart and aorta was loc alized by in vitro autoradiography with [I-125]351A, while fibrosis wa s identified by light microscopy in sections stained with collagen spe cific picrosirius red. Tissue was obtained at 2, 4, and 6 weeks from v arious experimental groups: unoperated, untreated, age- and sex-matche d controls; age- and sex-matched uninephrectomized control rats on a h igh sodium diet; and rats that had received either aldosterone (ALDO) or angiotensin II (AII). Compared with controls, we found ACE binding (1) unchanged after 2 weeks of ALDO, but increased in the adventitia o f intramural coronary arteries after 4 weeks, in keeping with the peri vascular fibrosis that appeared in each ventricle; (2) markedly increa sed after 6 weeks of ALDO, where it not only involved coronary vessels but also microscopic scars that appeared in atria and ventricles; (3) increased in the coronary adventitia and sites of scarring, each of w hich were present 2 weeks after AII; and (4) markedly increased after 4 and 6 weeks of AII as fibrosis became more extensive. Thus tissue AC E is closely related to-and a marker of-the fibrosis that appears in r esponse to chronic ALDO or AII administration. It appears that this hy drolase may be an integral component of fibrous tissue formation and t hat it operates independent of circulating renin and angiotensin pepti des.