Exercise training reverses age-related decrements in endothelium-dependent dilation in skeletal muscle feed arteries

J Appl Physiol (1985). 2009 Jun;106(6):1925-34. doi: 10.1152/japplphysiol.91232.2008. Epub 2009 Mar 19.

Abstract

We tested two hypotheses, first that exercise training reverses age-related decrements in endothelium-dependent dilation in soleus muscle feed arteries and second that this improved endothelium-dependent dilation is the result of increased nitric oxide (NO) bioavailability due to increased content and phosphorylation of endothelial NO synthase (eNOS) and/or increased antioxidant enzyme content. Young (2 mo) and old (22 mo) male Fischer 344 rats were exercise trained (Ex) or remained sedentary (Sed) for 10-12 wk, yielding four groups of rats: 1) young Sed (4-5 mo), 2) young Ex (4-5 mo), 3) old Sed (24-25 mo), and 4) old Ex (24-25 mo). Soleus muscle feed arteries (SFA) were isolated and cannulated with two glass micropipettes for examination of endothelium-dependent (ACh) and endothelium-independent [sodium nitroprusside (SNP)] vasodilator function. To determine the mechanism(s) by which exercise affected dilator responses, ACh-induced dilation was assessed in the presence of N(omega)-nitro-l-arginine (l-NNA; to inhibit NO synthase), indomethacin (Indo; to inhibit cyclooxygenase), and l-NNA + Indo. Results indicated that ACh-induced dilation was blunted in old Sed SFA relative to young Sed SFA. Exercise training improved ACh-induced dilation in old SFA such that vasodilator responses in old Ex SFA were similar to young Sed and young Ex SFA. Addition of l-NNA, or l-NNA + Indo, abolished the exercise effect. Immunoblot analysis revealed that extracellular superoxide dismutase (SOD) protein content was increased by training in old SFA, whereas eNOS and SOD-1 protein content were not altered. Addition of exogenous SOD, or SOD + catalase, improved ACh-induced dilation in old Sed SFA such that vasodilator responses were similar to young Sed SFA. Addition of l-NNA abolished the effect of exogenous SOD in old Sed arteries. Collectively, these results indicate that exercise training reverses age-induced endothelial dysfunction in SFA by increasing NO bioavailability and that increases in vascular antioxidant capacity may play an integral role in the improvement in endothelial function.

Publication types

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

MeSH terms

  • Acetylcholine / pharmacology
  • Aging / metabolism*
  • Animals
  • Arteries / drug effects
  • Arteries / metabolism*
  • Catalase / antagonists & inhibitors
  • Catalase / pharmacology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Indomethacin / pharmacology
  • Male
  • Muscle, Skeletal / blood supply*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Nitroarginine / pharmacology
  • Nitroprusside / pharmacology
  • Physical Conditioning, Animal*
  • Rats
  • Rats, Inbred F344
  • Recovery of Function
  • Superoxide Dismutase / antagonists & inhibitors
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase / pharmacology
  • Vasodilation

Substances

  • Enzyme Inhibitors
  • Nitroprusside
  • Nitroarginine
  • Nitric Oxide
  • Catalase
  • Nitric Oxide Synthase
  • Superoxide Dismutase
  • Acetylcholine
  • Indomethacin