Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarction.
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 (AT(1)-receptor and AT(2)-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 AT(1)-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 AT(1)-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 AT(2)-receptor subtype was observed. Hence, potential cardioprotective effects of the AT(1)-receptor antagonist are proposed.
El-Sabban
M E
ME
Department of Human Morphology, Amercian University of Beirut, Beirut, 11-0236, Lebanon.
Hassan
K A
KA
Birbari
A E
AE
Bitar
K M
KM
Bikhazi
A B
AB
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D006332:Cardiomegaly / Q000473:pathology; D002921:Cicatrix / Q000473:pathology; D003326:Coronary Circulation / Q000187:drug effects; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D007700:Kinetics; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D015415:Biomarkers; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II