Fibrosis and myocardial ACE: possible substrate and independence from circulating angiotensin II.
In order to determine the relation between myocardial fibrosis and (1) angiotensin converting enzyme (ACE) binding density, (2) receptor binding of ACE-related peptides, angiotensin II (AngII) and bradykinin (BK), and (3) the regulation of myocardial ACE by circulating Ang II, we used in vitro quantitative autoradiography to localize and assess ACE ([125I]351A), AngII receptor (125I[Sar1, IIe8]AngII), and BK receptor ([125I]Tyr8) binding densities in the rat myocardium. The experimental groups were (1) AngII (9 micrograms/h subcutaneously) or aldosterone (0.75 microgram/h subcutaneously in uninephrectomized rats on a high-sodium diet) administered by implanted minipump to chronically increase or decrease circulating AngII, respectively, (2) unoperated, untreated age- and sex-matched control rats, and (3) age- and sex-matched uninephrectomized control rats on a high-sodium diet. In the same heart studied at 2, 4, and 6 weeks of hormone treatment, serial sections were assessed for myocardial (hematoxylin and eosin) and fibrillar collagen (picrosirius red) morphology. The authors found that (1) marked ACE binding was coincident with sites of fibrous tissue that appeared in both ventricles as either a perivascular fibrosis of intramyocardial coronary arterioles or microscopic scarring in response to AngII or aldosterone infusion, (2) ACE binding was independent of circulating AngII, (3) BK, not AngII, receptor binding density was markedly increased at fibrous tissue sites, and (4) high-density ACE and BK receptor binding were anatomically coincident. Thus, in these experimental models, ACE is related to fibrous tissue formation where it may use BK, not angiotensin I, as a substrate, and its binding density is independent of circulating AngII.
Sun
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Y
Department of Internal Medicine, University of Missouri Health Sciences Center, Columbia, USA.
Weber
K T
KT
D000450:Aldosterone / Q000097:blood / Q000378:metabolism; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D004719:Endomyocardial Fibrosis / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism; D018002:Receptors, Bradykinin / Q000097:blood / Q000378:metabolism*
D011945:Receptors, Angiotensin; D018002:Receptors, Bradykinin; D000804:Angiotensin II; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A