Effects of oral N-acetylcysteine on walking capacity, leg reactive hyperemia, and inflammatory and angiogenic mediators in patients with intermittent claudication

Am J Physiol Heart Circ Physiol. 2015 Sep;309(5):H897-905. doi: 10.1152/ajpheart.00158.2015. Epub 2015 Jun 26.


Increased oxidative stress and inflammation contribute to impaired walking capacity and endothelial dysfunction in patients with intermittent claudication (IC). The goal of the study was to determine the effects of oral treatment with the antioxidant N-acetylcysteine (NAC) on walking capacity, leg postocclusive reactive hyperemia, circulating levels of inflammatory mediators, and whole blood expression of angiogenic mediators in patients with IC. Following a double-blinded randomized crossover design, 10 patients with IC received NAC (1,800 mg/day for 4 days plus 2,700 mg before the experimental session) and placebo (PLA) before undergoing a graded treadmill exercise test. Leg postocclusive reactive hyperemia was assessed before and after the test. Blood samples were taken before and after NAC or PLA ingestions and 5 and 30 min after the exercise test for the analysis of circulating inflammatory and angiogenic markers. Although NAC increased the plasma ratio of reduced to oxidized glutathione, there were no differences between experimental sessions for walking tolerance and postocclusive reactive hyperemia. Plasma concentrations of soluble vascular cell adhesion protein-1, monocyte chemotactic protein-1, and endothelin-1 increased similarly following maximal exercise after PLA and NAC (P < 0.001). Whole blood expression of pro-angiogenic microRNA-126 increased after maximal exercise in the PLA session, but treatment with NAC prevented this response. Similarly, exercise-induced changes in whole blood expression of VEGF, endothelial nitric oxide synthase and phosphatidylinositol 3-kinase R2 were blunted after NAC. In conclusion, oral NAC does not increase walking tolerance or leg blood flow in patients with IC. In addition, oral NAC prevents maximal exercise-induced increase in the expression of circulating microRNA-126 and other angiogenic mediators in patients with IC.

Keywords: N-acetylcysteine; blood flow; intermittent claudication; microRNA-126; microRNAs.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / therapeutic use*
  • Administration, Oral
  • Aged
  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use*
  • Chemokine CCL2 / blood
  • Endothelins / blood
  • Humans
  • Hyperemia / blood
  • Hyperemia / drug therapy*
  • Inflammation / blood
  • Inflammation / drug therapy
  • Intermittent Claudication / blood
  • Intermittent Claudication / drug therapy*
  • Leg / blood supply
  • Male
  • MicroRNAs / blood
  • Middle Aged
  • Nitric Oxide Synthase Type III / blood
  • Phosphatidylinositol 3-Kinases / blood
  • Vascular Cell Adhesion Molecule-1 / blood
  • Vascular Endothelial Growth Factor A / blood
  • Walking*


  • Antioxidants
  • CCL2 protein, human
  • Chemokine CCL2
  • Endothelins
  • MIRN126 microRNA, human
  • MicroRNAs
  • Vascular Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • Nitric Oxide Synthase Type III
  • Phosphatidylinositol 3-Kinases
  • Acetylcysteine