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

J Physiol. 2009 Aug 1;587(Pt 15):3885-97. doi: 10.1113/jphysiol.2009.172221. Epub 2009 Jun 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Antioxidants / pharmacology
  • Arterioles / metabolism*
  • Biopterin / analogs & derivatives
  • Biopterin / metabolism
  • Cyclic N-Oxides / pharmacology
  • Hydrogen Peroxide / metabolism
  • Male
  • Models, Animal
  • Muscle, Skeletal / blood supply*
  • Muscle, Skeletal / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism*
  • Oxygen / metabolism
  • Physical Conditioning, Animal / physiology*
  • Rats
  • Rats, Inbred F344
  • Reactive Oxygen Species / metabolism
  • Spin Labels
  • Vascular Resistance / physiology
  • Vasodilation / drug effects


  • Antioxidants
  • Cyclic N-Oxides
  • Reactive Oxygen Species
  • Spin Labels
  • Biopterin
  • Nitric Oxide
  • Hydrogen Peroxide
  • Nitric Oxide Synthase Type III
  • sapropterin
  • Oxygen
  • tempol