Fa. Khawli et Mb. Reid, N-ACETYLCYSTEINE DEPRESSES CONTRACTILE FUNCTION AND INHIBITS FATIGUE OF DIAPHRAGM IN-VITRO, Journal of applied physiology, 77(1), 1994, pp. 317-324
We have previously shown that antioxidant enzymes (superoxide dismutas
e and catalase) depress contractility of unfatigued diaphragm fiber bu
ndles and inhibit development of acute fatigue. In the present study,
we tested for similar effects of N-acetyl-cysteine (NAC), a nonspecifi
c antioxidant approved for clinical use. Diaphragms were excised from
deeply anesthetized rats. Fiber bundles were removed, mounted isometri
cally at 37 degrees C, and stimulated directly using supramaximal curr
ent intensity. Studies of unfatigued muscle showed that 10 mM NAC redu
ced peak twitch stress (P < 0.0001), shortened time to peak twitch str
ess (P < 0.002), and shifted the stress-frequency curve down and to th
e right (P < 0.05). Fiber bundles incubated in 0.1-10 mM NAC exhibited
a dose-dependent decrease in relative stresses developed during 30-Hz
contraction (P < 0.0001) with no change in maximal tetanic (200 Hz) s
tress. NAC (10 mM) also inhibited acute fatigue. Throughout 10 min of
intermittent contraction at 30-40 Hz, treated bundles developed higher
stresses than time-matched control bundles (P < 0.0001). NAC concentr
ations greater than or equal to 30 mM were toxic, causing a prompt irr
eversible decrease in maximal tetanic stress (P < 0.0001). Because NAC
effects mimic the effects of other antioxidant agents with different
mechanisms of action, we conclude that exogenous antioxidants exert st
ereotypical effects on contractile function that differ between unfati
gued and fatiguing muscle. Unlike antioxidant enzymes, however, NAC ha
s been approved for clinical use and may be used in future studies of
human muscle fatigue.