INDUCTION OF APOPTOSIS IN MYOCARDIAL-INFARCTION AND ITS POSSIBLE RELATIONSHIP TO NITRIC-OXIDE SYNTHASE IN MACROPHAGES

Activated macrophages produce nitric oxide through the inducible form of nitric oxide synthase (iNOS). Previously, a significant increase of iNOS activity in macrophages in infarcted rabbit heart tissue was obs erved, The present study is concerned with the induction of apoptosis iii macrophages and cardiomyocytes in infarcted rabbit heart tissue, T he left anterior descending artery of rabbits was ligated, The heart w as excised five hours, one, two, three, ten and twenty days later, and DNA was extracted from infarcted and non-infarcted region and subject ed to electrophoresis, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) was carried out, and iNOS activi ty was measured by conversion of L-[C-14]-arginine to L-[C-14]-citrull ine. Positive staining by TUNEL was seen in some cardiomyocytes five h ours after coronary ligation and on postoperative day (POD) 1; internu cleosomal DNA fragmentation was not noted. On POD 2 and 3, many infilt rating cells, immunohistochemically identified as macrophages, were po sitively stained by TUNEL; DNA fragmentation was also present, Apoptos is was not found on POD 10 and 20, The peak activity of iNOS was noted on POD 3, which corresponded with the induction of apoptosis. It is t empting to speculate that a causal relationship exists between increas ed;iNOS formation and induction of apoptosis in macrophages in infarct ed rabbit heart tissue.