Increased inducible nitric oxide synthase expression contributes to myocardial dysfunction and higher mortality after myocardial infarction in mice

Background-Inducible nitric oxide synthase (iNOS) is expressed in the myoca rdium after myocardial infarction (MI) and in heart failure. Its pathophysi ological role in these conditions, however, is not clear. We hypothesized t hat increased NO production from iNOS expression causes myocardial dysfunct ion and results in higher mortality after MI. Methods and Results-Ml was induced by left coronary artery ligation in iNOS (-/-) mutant and wild-type mice. Mortality was followed up for 30 days. MI resulted in a significant increase in mortality in both iNOS(-/-) and wild- type mice compared with sham operation (P <0.01). Mortality was significant ly decreased and LV myocardial contractility was increased, however, in iNO S(-/-) mice compared with the wild-type mice (P <0.05). Five days after MI, myocardial iNOS mRNA expression, plasma nitrate and nitrite concentrations , and myocardial and plasma nitrotyrosine levels were significantly increas ed in wild-type compared with iNOS(-/-) mutant mice (P <0.05). Both basal L V +dP/dt and its response to dobutamine were significantly increased in iNO S(-/-) compared with the wild-type mice (P <0.05). Conclusions-Increased NO production from iNOS expression contributes to myo cardial dysfunction and mortality after MI in mice.