title: N-acetylcysteine attenuates the decline in muscle Na+,K+-pump activity and delays fatigue during prolonged exercise in humans.
abstract: 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 (%Deltaactivity) at 45 min (P < 0.05) but not at fatigue. When expressed relative to work done, the %Deltaactivity-to-work ratio was attenuated by NAC at 45 min and fatigue (P < 0.005). The rise in plasma [K(+)] during exercise and the Delta[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.
authors.affiliation: School of Human Movement, Recreation and Performance, Victoria University, PO Box 14428, Melbourne, Victoria, Australia, 8001. michael.mckenna@vu.edu.au
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McKenna
authors.forename: Ivan
authors.initials: I
authors.lastname: Medved
authors.forename: Craig A
authors.initials: CA
authors.lastname: Goodman
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Brown
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Bjorksten
authors.forename: Kate T
authors.initials: KT
authors.lastname: Murphy
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Petersen
authors.forename: Simon
authors.initials: S
authors.lastname: Sostaric
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Gong
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000136:Acid-Base Equilibrium / Q000502:physiology; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005080:Exercise Test; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018763:Muscle Fatigue / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D010807:Physical Endurance / Q000502:physiology*; D011188:Potassium / Q000097:blood; D017382:Reactive Oxygen Species; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000502:physiology
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C045349:3-O-methyl-fluorescein phosphatase; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D000111:Acetylcysteine