Effect of a high-salt diet on oxidant enzyme activity in skeletal muscle microcirculation

Am J Physiol Heart Circ Physiol. 2002 Feb;282(2):H395-402. doi: 10.1152/ajpheart.0354.2001.


Increased salt intake attenuates the endothelium-dependent dilation of skeletal muscle arterioles by abolishing local nitric oxide (NO) activity. There is evidence of oxidative stress in arteriolar and venular walls of rats fed a high-salt diet, and depressed arteriolar responses to acetylcholine (ACh) in these rats are reversed by scavengers of reactive oxygen species (ROS). In this study, we tested the hypothesis that this salt-dependent increase in microvascular ROS and the resulting attenuation of endothelium-dependent dilation are due to increased expression and/or activity of oxidant enzymes in the microvascular wall. Resting arteriolar and venular wall oxidant activity, as assessed by tetranitroblue tetrazolium reduction, was consistently higher in the spinotrapezius muscle of rats fed a high-salt diet (7% NaCl, HS) for 4-5 wk than in those fed a normal diet (0.45% NaCl, NS) for the same duration. Western analysis of protein from isolated microvessels showed no difference between HS and NS rats in the expression of NAD(P)H oxidase or xanthine oxidase. Inhibition of NAD(P)H oxidase and/or xanthine oxidase with diphenyleneiodonium chloride and oxypurinol, respectively, reduced resting arteriolar wall oxidant activity to normal levels in HS rats but had no effect in NS rats, suggesting that the basal activities of NAD(P)H oxidase and xanthine oxidase are increased in HS microvessels. However, inhibition of these enzymes in HS rats did not restore normal arteriolar responses to ACh, suggesting that this stimulus activates an alternate source of ROS that eliminates the role of NO in the subsequent dilation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Capillaries / enzymology
  • Endothelium, Vascular / enzymology
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Male
  • Muscle, Skeletal / blood supply*
  • NADPH Oxidases / antagonists & inhibitors
  • NADPH Oxidases / metabolism*
  • Nitric Oxide / metabolism
  • Onium Compounds / pharmacology
  • Oxypurinol / pharmacology
  • Phosphoproteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Chloride, Dietary / pharmacology*
  • Vasodilation / drug effects
  • Xanthine Oxidase / antagonists & inhibitors
  • Xanthine Oxidase / metabolism*


  • Enzyme Inhibitors
  • Onium Compounds
  • Phosphoproteins
  • Sodium Chloride, Dietary
  • neutrophil cytosol factor 67K
  • Nitric Oxide
  • diphenyleneiodonium
  • Xanthine Oxidase
  • NADPH Oxidases
  • Oxypurinol