Protective Vascular and Cardiac Effects of Inducible Nitric Oxide Synthase in Mice with Hyperhomocysteinemia

摘要: Diet-induced hyperhomocysteinemia produces endothelial and cardiac dysfunction promotes thrombosis through a mechanism proposed to involve oxidative stress. Inducible nitric oxide synthase (iNOS) is upregulated in can generate superoxide. We therefore tested the hypothesis that iNOS mediates adverse oxidative, vascular, thrombotic, effects of hyperhomocysteinemia. Mice deficient (Nos2−/−) their wild-type (Nos2+/+) littermates were fed high methionine/low folate (HM/LF) diet induce mild hyperhomocysteinemia, with 2-fold increase plasma total homocysteine (P<0.001 vs. control diet). Hyperhomocysteinemic Nos2+/+ mice exhibited cerebral arterioles, impaired dilatation acetylcholine but not nitroprusside, enhanced susceptibility carotid artery thrombosis, shortened times occlusion following photochemical injury (P<0.05 Nos2−/− had decreased rather than increased responses mice). also thrombotic mice), deficiency failed protect from or accelerated Deficiency did alter myocardial infarct size significantly superoxide production HM/LF These findings suggest endogenous protects from, exacerbates, dysfunction, hyperhomocysteinemia-associated ischemia-reperfusion injury. In setting functions blunt stress functioning as source