REGIONAL CHANGES IN ANGIOTENSIN-II RECEPTOR DENSITY AFTER EXPERIMENTAL MYOCARDIAL-INFARCTION

The plasma and cardiac renin-angiotensin systems may be activated afte r myocardial infarction. The myocardium may therefore be exposed to in creased concentrations of angiotension II, which may contribute to myo cardial injury. The purpose of this study was to identify the potentia l sites of action of angiotensin II in the infarcted heart. Myocardial infarction was induced in rats by left coronary artery ligation, and the hearts were removed for study after 18 h, 7 days, or 8 months. The regional ventricular angiotensin II receptor density was assessed by [I-125](Sar(1),Ile(8))angiotensin II binding and quantitative autoradi ography. The [I-125](Sar(1),Ile(8))angiotensin II binding was unchange d at 18 h, but was increased at 7 days in the infarcted region of the left ventricle (73.2 +/- 3.2 amol/mm(2), mean +/- S.E.M.) compared wit h the non-infarcted region (1.6 +/- 0.2 amol/mm(2), P<0.0001) and with the left ventricular myocardium of sham-operated control animals (1.3 +/- 0.1 amol/mm(2), P<0.0001). The increased [I-125](Sar(1),Ile(8))an giotensin II binding density was still present, but diminished, at 8 m onths after coronary ligation (49.0 +/- 5.7 amol/mm(2), P<0.0001 nu co ntrol, P=0.0058 nu 7-day infarcts). The increased binding of [I-125](S ar(1),Ile(8))angiotensin II was antagonised by losartan, an AT(1) rece ptor antagonist, but not by an AT(2) receptor antagonist. Microautorad iography of [I-125](Sar(1),Ile(8)) angiotensin II, and assessment of c ollagen deposition using picrosirius staining and immunostaining demon strated that the regional increase in AT(1) receptor density in the in farcted region of myocardium was associated with fibroblast infiltrati on and collagen deposition. The infarct scar and the cardiac fibroblas ts within it express high levels of angiotension II receptors and ther efore represent potential targets for the actions of angiotensin II af ter myocardial infarction. 1996 Academic Press Limited