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Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarction

Department of Human Morphology, Faculty of Medicine, American University of Beirut

Khaled A Hassan

Department of Physiology, American University of Beirut

Adel E Birbari

Department of Physiology, American University of Beirut

Khalil M Bitar

Department of Physics, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon

Anwar B Bikhazi

Department of Physiology, American University of Beirut, ab04@ aub.lb.edu

Clinical evidence points to a role for angiotensin II (Ang II) in the post-infarction remodelling of cardiac hypertrophy. The present study was designed to investigate the remodelling process in an animal model of myocardial infarction (MI) using the following criteria: 1) histological studies to examine the re-vascularisation process and collagen deposition in different regions of the myocardium; 2) histological evidence to investigate the cell type distribution using cell-specific markers; 3) histological and Western blot analysis to localise Ang II receptor subtypes (AT₁-receptor and AT₂-receptor) and to study their regulation; 4) kinetics of the binding of Ang II to its receptors in a heart perfusion model; and 5) to assess the effect of the Ang II antagonist (losartan) on these parameters.

MI was induced by ligation of the left anterior descending coronary artery of Sprague-Dawley rats. Four different animal groups were established: 1) sham-operated, non-treated; 2) sham-operated, treated with losartan; 3) myocardial infarct, non-treated; and

4) myocardial infarct, treated with losartan. In infarcted rat hearts, fibroblasts and collagen types I and III increased in the remnant viable region of the left ventricle compared with sham-operated rats. One month of losartan treatment in myocardial infarcted rats revealed insignificant changes in fibroblasts and collagen types I and III compared with sham controls. Also, myocardial infarction increased AT₁-receptor protein levels compared with sham-operated controls, as judged by Western blotting. In losartan-treated myocardial infarct animals, no changes were detected at the level of AT₁-receptor expression compared with non-treated myocardial infarct rats. Binding studies of Ang II on endothelial cell lining and directly on myocytes in sham-operated and infarcted perfused rat hearts revealed that, in myocardial infarcted-animals, Ang II binding affinity increased both in the endothelium and in myofibres. This may be considered a major putative effect of the peptide in potentiating the pharmacodynamics of hypertrophy. In losartan-treated myocardial infarcted-animals, a marked increase in the binding affinities of Ang II for the AT₂-receptor subtype was observed. Hence, potential cardioprotective effects of the AT ₁-receptor antagonist are proposed.

Key Words: angiotensin • myocardial infarction • remodelling • losartan

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 1, No. 4, 369-378 (2000)
DOI: 10.3317/jraas.2000.069


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by El-Sabban, M. E Articles by Bikhazi, A. B Search for Related Content PubMed PubMed Citation Articles by El-Sabban, M. E Articles by Bikhazi, A. B Social Bookmarking                         What's this?