N-acetylcysteine attenuates the decline in muscle Na+,K+-pump activity and delays fatigue during prolonged exercise in humans

• Published in: The Journal of physiology Vol. 576; no. 1; pp. 279 - 288
• Main Authors: McKenna, Michael J., Medved, Ivan, Goodman, Craig A., Brown, Malcolm J., Bjorksten, Andrew R., Murphy, Kate T., Petersen, Aaron C., Sostaric, Simon, Gong, Xiaofei
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 01.10.2006; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Acetylcysteine - pharmacology; Acid-Base Equilibrium - physiology; Adult; Cross-Over Studies; Double-Blind Method; Exercise Test; Free Radical Scavengers - pharmacology; Humans; Male; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle Fatigue - drug effects; Muscle Fatigue - physiology; Muscle, Skeletal - drug effects; Muscle, Skeletal - enzymology; Muscle, Skeletal - physiology; Physical Endurance - physiology; Potassium - blood; Reactive Oxygen Species; Skeletal Muscle and Exercise; Sodium-Potassium-Exchanging ATPase - drug effects; Sodium-Potassium-Exchanging ATPase - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2006.115352

Reactive oxygen species (ROS) have been linked with both depressed Na + ,K + -pump activity and skeletal muscle fatigue. This study investigated N -acetylcysteine (NAC) effects on muscle Na + ,K + -pump activity and potassium (K + ) regulation during prolonged, submaximal endurance exercise. Eight well-trained subjects participated in a double-blind, randomised, crossover design, receiving either NAC or saline (CON) intravenous infusion at 125 mg kg −1 h −1 for 15 min, then 25 mg kg −1 h −1 for 20 min prior to and throughout exercise. Subjects cycled for 45 min at 71% , then continued at 92% until fatigue. Vastus lateralis muscle biopsies were taken before exercise, at 45 min and fatigue and analysed for maximal in vitro Na + ,K + -pump activity (K + -stimulated 3-O-methyfluorescein phosphatase; 3-O-MFPase). Arterialized venous blood was sampled throughout exercise and analysed for plasma K + and other electrolytes. Time to fatigue at 92% was reproducible in preliminary trials ( c.v. 5.6 ± 0.6%) and was prolonged with NAC by 23.8 ± 8.3% (NAC 6.3 ± 0.5 versus CON 5.2 ± 0.6 min, P < 0.05). Maximal 3-O-MFPase activity decreased from rest by 21.6 ± 2.8% at 45 min and by 23.9 ± 2.3% at fatigue ( P < 0.05). NAC attenuated the percentage decline in maximal 3-O-MFPase activity (%Δactivity) at 45 min ( P < 0.05) but not at fatigue. When expressed relative to work done, the %Δactivity-to-work ratio was attenuated by NAC at 45 min and fatigue ( P < 0.005). The rise in plasma [K + ] during exercise and the Δ[K + ]-to-work ratio at fatigue were attenuated by NAC ( P < 0.05). These results confirm that the antioxidant NAC attenuates muscle fatigue, in part via improved K + regulation, and point to a role for ROS in muscle fatigue.