Effects of ageing and exercise training on eNOS uncoupling in skeletal muscle resistance arterioles.
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.
Sindler
Amy L
AL
Department of Physiology and Pharmacology, West Virginia University, School of Medicine, Morgantown, WV 26506, USA.
Delp
Michael D
MD
Reyes
Rafael
R
Wu
Guoyao
G
Muller-Delp
Judy M
JM
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001160:Arterioles / Q000378:metabolism*; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D013113:Spin Labels; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D000975:Antioxidants; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D001708:Biopterins; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin; D010100:Oxygen; C001803:tempol