Absence of Inducible Nitric Oxide Synthase Reduces Myocardial Damage During Ischemia Reperfusion in Streptozotocin-Induced Hyperglycemic Mice

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Abstract
We investigated the role of inducible nitric oxide synthase (iNOS) on ischemic myocardial damage and angiogenic process in genetically deficient iNOS (iNOS−/−) mice and wild-type littermates (iNOS+/+), with and without streptozotocin-induced (70 mg/kg intravenously) diabetes. After ischemia (25 min) and reperfusion (120 min), both iNOS+/+ and iNOS−/− diabetic mice (blood glucose 22 mmol/l) had myocardial infarct size greater than their respective nondiabetic littermates (P < 0.01). Myocardial infarct size (P < 0.05), apoptotic index (P < 0.005), and tissue levels of tumor necrosis factor (P < 0.01), interleukin-6 (P < 0.01), and interleukin-18 (P < 0.01) were higher in nondiabetic iNOS−/− mice compared with nondiabetic iNOS+/+ mice. As compared with diabetic iNOS−/− mice, diabetic iNOS+/+ mice showed a greater infarct size (P < 0.01) associated with the highest tissue levels of nitrotyrosine and proinflammatory cytokines, as well as apoptosis. The beneficial role of iNOS in modulating defensive responses against ischemia/reperfusion injury seems to be abolished in diabetic mice.