Effects of ageing and exercise training on eNOS uncoupling in skeletal muscle resistance arterioles

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Blackwell Science Inc

RESUMO

Reduced availability of tetrahydrobiopterin (BH4) contributes to the age-related decline of nitric oxide (NO)-mediated vasodilatation of soleus muscle arterioles. Depending on availability of substrate and/or necessary co-factors, endothelial nitric oxide synthase (eNOS) can generate NO and/or superoxide (O2−). We evaluated the effects of age and chronic exercise on flow-induced vasodilatation and levels of NO and O2− in soleus muscle arterioles. Young (3 months) and old (22 months) male rats were exercise trained or remained sedentary (SED) for 10 weeks. Flow-stimulated NO and O2−, as well as BH4 and l-arginine content, were determined in soleus muscle arterioles. Flow-induced vasodilatation was assessed under control conditions and during the blockade of O2− and/or hydrogen peroxide. Exercise training enhanced flow-induced vasodilatation in arterioles from young and old rats. Old age reduced, and exercise training restored, BH4 content and flow-stimulated NO availability. Flow-stimulated, eNOS-derived O2− levels were higher in arterioles from old SED compared to those from young SED rats. Exercise training increased flow-stimulated eNOS-derived O2− levels in arterioles from young but not old rats. O2− scavenging with Tempol reduced flow-induced vasodilatation from all groups except young SED rats. Addition of catalase to Tempol-treated arterioles eliminated flow-induced vasodilatation in arterioles from all groups. Catalase reduced flow-induced vasodilatation from all groups. In Tempol-treated arterioles, flow-induced vasodilatation was restored by deferoxamine, an iron chelator. These data indicate that uncoupling of eNOS contributes to the age-related decline in flow-induced vasodilatation; however, reactive oxygen species are required for flow-induced vasodilatation in soleus muscle arterioles from young and old rats.

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