Differential expression of three types of nitric oxide synthase in both infarcted and non-infarcted left ventricles after myocardial infarction in the rat

In the present report we investigated the differential expression of three types of nitric oxide synthase (NOS) in the left ventricle after myocardial infarction in rats. One, 3, 7, 14, 28 and 56 days (n=6-12 for each group) after ligation of a coronary artery, tissue samples were obtained from infa rcted and non-infarcted tissues. The mRNA and protein levels of neuronal (n ) NOS, endothelial (e) NOS and inducible (i) NOS were sequentially determin ed by semi-quantitative reverse transcription-polymerase chain reaction and Western blotting. Progressive left ventricular dilatation and gradual redu ction in fractional shortening were confirmed by echocardiography. The expr ession levels of nNOS were significantly increased 1, 3 and 7 days post-inf arct compared to those of sham-operated rats in both the infarcted (P<0.01) and non-infarcted regions (P<0.01). Immunohistochemical analysis showed th at nNOS was localized in nerve fibers in the left ventricle and that the nu mber of positive fibers after myocardial infarction had increased compared to that in sham-operated rats. With regard to eNOS, no significant changes in expression levels were detected between infarcted hearts and sham-operat ed controls. The level of iNOS expression peaked three days post-infarct an d then decreased in the infarcted tissue, whereas it increased one day post -infarct, peaked at 14 and 28 days post-infarct and was still elevated in t he chronic stage in the ventricular septum. iNOS immunoreactivity was detec ted in spared cardiomyocytes and macrophages in the infarcted region, and i n cardiomyocytes in the ventricular septum. The expressions of three types of NOS were differentially regulated and iNOS produced in the non-infarcted region may contribute to the progression of heart failure after myocardial infarction in rats. (C) 2000 Elsevier Science Ireland Ltd. All rights rese rved.