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Effects of ageing and exercise training on eNOS uncoupling in skeletal muscle resistance arterioles
Author(s) -
Sindler Amy L.,
Delp Michael D.,
Reyes Rafael,
Wu Guoyao,
MullerDelp Judy M.
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.172221
Subject(s) - vasodilation , sed , medicine , endocrinology , nitric oxide , enos , chemistry , arteriole , soleus muscle , skeletal muscle , microcirculation , nitric oxide synthase
Reduced availability of tetrahydrobiopterin (BH 4 ) 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 (O 2 − ). We evaluated the effects of age and chronic exercise on flow‐induced vasodilatation and levels of NO and O 2 − 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 O 2 − , as well as BH 4 and l ‐arginine content, were determined in soleus muscle arterioles. Flow‐induced vasodilatation was assessed under control conditions and during the blockade of O 2 − and/or hydrogen peroxide. Exercise training enhanced flow‐induced vasodilatation in arterioles from young and old rats. Old age reduced, and exercise training restored, BH 4 content and flow‐stimulated NO availability. Flow‐stimulated, eNOS‐derived O 2 − levels were higher in arterioles from old SED compared to those from young SED rats. Exercise training increased flow‐stimulated eNOS‐derived O 2 − levels in arterioles from young but not old rats. O 2 − 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.