Up-regulation of AT1 and AT(2) receptors in postinfarcted hypertrophied myocytes and stretch-mediated apoptotic cell death

To determine whether up-regulation of AT(1) and AT(2) receptors occurred in hypertrophied myocytes after infarction and whether AT(2) played a role in stretch-mediated apoptosis, left ventricular myocytes were dissociated fro m the surviving portion of the wall 8 days after coronary occlusion and car diac failure in rats. Control cells were obtained from sham-operated animal s. Myocytes were stretched in an equibiaxial stretch apparatus and angioten sin II (Ang II) formation and cell death were measured 3 and. 12 hours late r. AT(1) and AT(2) proteins were evaluated in freshly isolated myocytes and after stretch. The effects of AT(1) and AT(2) antagonists on stretch-induc ed Ang II synthesis and apoptosis were also established. Myocardial infarct ion increased AT(1) and AT(2) in myocytes and stretch further up-regulated these receptors. Ang II levels were higher in postinfarcted myocytes and th is peptide increased with the duration of stretch in both groups of cells. Similarly, apoptosis increased with time in control and postinfarcted myocy tes. Absolute values of Ang II and apoptosis were greater in myocytes from infarcted hearts at 3 and 12 hours after stretch. Addition of AT(1) blocker to cultures Inhibited stretch-activated apoptosis in both myocyte populati ons as well as the generation of Ang II in postinfarcted myocytes. In contr ast, AT(2) antagonists had no impact on these cellular events. In conclusio n, Ang II stimulated cell death through AT(1) receptor activation, whereas Ligand binding to AT(2) receptor did not alter Ang II concentration and apo ptosis in normal and postinfarcted hypertrophied myocytes.