title: Angiotensin-converting enzyme and myocardial fibrosis in the rat receiving angiotensin II or aldosterone.
abstract: Angiotensin-converting enzyme (ACE) is present in tissues composed largely of fibrillar collagen such as heart valves, the adventitia of great vessels and intramyocardial coronary arteries, and the scar that follows 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 purpose we selected experimental models that simulate primary and secondary hyperaldosteronism, each of which are associated with the appearance of myocardial fibrosis. ACE in the excised heart and aorta was localized by in vitro autoradiography with [125I]351A, while fibrosis was identified by light microscopy in sections stained with collagen specific picrosirius red. Tissue was obtained at 2, 4, and 6 weeks from various experimental groups: unoperated, untreated, age- and sex-matched controls; age- and sex-matched uninephrectomized control rats on a high 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 of intramural coronary arteries after 4 weeks, in keeping with the perivascular fibrosis that appeared in each ventricle; (2) markedly increased 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 which were present 2 weeks after AII; and (4) markedly increased after 4 and 6 weeks of AII as fibrosis became more extensive.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Internal Medicine, University of Missouri-Columbia.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: A
authors.initials: A
authors.lastname: Ratajska
authors.forename: G
authors.initials: G
authors.lastname: Zhou
authors.forename: K T
authors.initials: KT
authors.lastname: Weber
mesh_terms: D000450:Aldosterone / Q000097:blood / Q000633:toxicity*; D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology*; D005355:Fibrosis; D006321:Heart / Q000187:drug effects*; D007457:Iodine Radioisotopes; D017706:Lisinopril / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology*; D009392:Nephrectomy; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000494:pharmacology
chemical_list: D007457:Iodine Radioisotopes; D012982:Sodium, Dietary; D000804:Angiotensin II; D000450:Aldosterone; D003094:Collagen; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A