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

Abstract

Increased oxidative stress and inflammation contribute to impaired walking capacity andendothelial 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, legpostocclusive reactive hyperemia, circulating levels of inflammatory mediators, and whole blood expression of angiogenic mediators inpatients with IC. Following a double-blinded randomized crossover design, 10 patients with IC received NAC (1,800 mg/day for 4 daysplus 2,700 mg before the experimental session) and placebo (PLA)before undergoing a graded treadmill exercise test. Leg postocclusivereactive 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 postocclusivereactive hyperemia. Plasma concentrations of soluble vascular cell adhesion protein-1, monocyte chemotactic protein-1, andendothelin-1 increased similarly following maximal exercise after PLA and NAC (P 0.001). Whole blood expression of pro-angiogenicmicroRNA-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, endothelialnitric oxide synthase and phosphatidylinositol 3-kinase R2 were blunted after NAC. In conclusion, oral NAC does not increasewalking tolerance or leg blood flow in patients with IC. In addition, oral NAC prevents maximal exercise-induced increase in the expressionof circulating microRNA-126 and other angiogenic mediators in patients with IC. (AU)