Inhibition of angiotensin-converting enzyme and attenuation of myocardial fibrosis by lisinopril in rats receiving angiotensin II.
High-density angiotensin-converting enzyme (ACE) binding is present in heart valve leaflets and the fibrous tissue that appears in the rat myocardium after either chronic administration of angiotensin II (AngII) or after myocardial infarction. This suggests that connective tissue ACE is independent of circulating AngII and that ACE may be an integral component of normal and pathologic tissue repair. To address this possibility the present study was undertaken. We sought to determine whether the ACE inhibitor lisinopril would attenuate fibrous tissue ACE binding and fibrous tissue formation in the myocardium of rats receiving AngII. Three experimental groups were examined: untreated, age-matched controls; rats receiving subcutaneous AngII (150 ng/min) by minipump for 2 weeks; and rats receiving AngII plus oral lisinopril (20 mg/kg/day) for 2 weeks. Cardiac ACE binding density was localized and quantified by in vitro autoradiography with [125I]-labeled 351A, a tyrosyl derivative of lisinopril, while fibrosis was identified by light microscopy in serial sections stained with picrosirius red. Hematoxylin and eosin and anti-fibronectin antibody were used to identify cardiac myocyte necrosis. Immunohistochemical labeling with alpha-smooth muscle actin was used to identify myofibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)
Sun
Y
Y
Department of Internal Medicine, University of Missouri-Columbia 65212, USA.
Ratajska
A
A
Weber
K T
KT
D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D005355:Fibrosis; D007150:Immunohistochemistry; D017706:Lisinopril / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D009336:Necrosis; D007703:Peptidyl-Dipeptidase A / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A