Alterations in angiotensin II receptor mediated signal transduction shortly after coronary artery constriction in the rat

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Abstract
Objective: The aim of the study was to determine the effect of coronary artery constriction on the density of angiotensin II receptors and on the effector responses coupled with these receptors on myocytes one week after surgical induction of coronary artery stenosis in rats. Methods: After induction of coronary artery stenosis and following the estimation of global cardiac performance, myocytes were enzymatically dissociated and radio- ligand binding studies were performed. In addition, the isotonic contractile performance, cytosolic calcium transients. and angiotensin II stimulated inositol phosphate generation in myocytes were measured in the presence and absence of the angiotensin II receptor subtype antagonist losartan. Results: After documenting left ventricular failure and right ventricular dysfunction, the expression and density of angiotensin II receptors in left ventricular niyocytes were evaluated and found to be increased 3.1 -fold and 4.1 -fold, respectively. Corresponding increases in right ventricular myocytes were 3.6-fold and 4.5-fold. In contrast, the quantity of the regulatory protein Gqα was not altered in either ventricle. Angiotensin I1 did not increase the generation of total inositol phosphates in left and right ventricular myocytes at maximum stimulation. However, the threshold for the formation of inositol phosphates was lowered in left ventricular myocytes of coronary narrowed rats. Measurements of single cell mechanics indicated that angiotensin I1 stimulation markedly improved the depression in myocyte function biventricularly. This inotropic effect was coupled with the restoration of cytosolic calcium. Conclusions: The upregulation of angiotensin I1 receptors on myocytes in this model of global ischaemia may be a compensatory mechanism ameliorating myocyte contractility in an attempt to sustain Ventricular pump function. Cardiovascular Research 1994;28:1564-1573

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