TY - JOUR
T1 - Buthionine sulfoximine treatment impairs rat diaphragm function
AU - Morales, Carlos F.
AU - Anzueto, Antonio
AU - Andrade, Francisco
AU - Brassard, James
AU - Levine, Stephanie M.
AU - Maxwell, Leo
AU - Lawrence, Richard A.
AU - Jenkinson, Stephen G
PY - 1994/4
Y1 - 1994/4
N2 - Activation of the glutathione (GSH) redox cycle with production of glutathione disulfide (GSSG) has been shown to occur in the diaphragm during inspiratory resistive loading (RB). Buthionine sulfoximine (BSO) lowers tissue GSH by irreversibly inhibiting the rate-limiting synthesis enzyme γ- glutamylcysteine synthetase. We investigated the effects of BSO on rat diaphragm function both at rest and after a period of RB. Rats in the RB groups underwent inspiratory RB until they were unable to sustain 70% of their maximal airway pressure. A portion of the diaphragm was analyzed for GSH and GSSG levels, and measurements of in vitro contractile properties included contraction times, maximal tetanic tension (Po), maximal twitch tension (Pt), and force frequency curves. BSO treatment produced a profound depletion of diaphragmatic GSH. Neither BSO nor RB alone significantly altered diaphragm contractile properties at this load of RB. But, in BSO-RB rats, there was a significant decrease in Pt, Po, and tetanic tension at all frequencies of stimulation compared with those in other groups. These data reveal that animals treated with BSO followed by inspiratory resistive loading exhibit marked diaphragm impairment, suggesting that GSH may play an important role in protecting the diaphragm from the stress induced by this resistive breathing protocol.
AB - Activation of the glutathione (GSH) redox cycle with production of glutathione disulfide (GSSG) has been shown to occur in the diaphragm during inspiratory resistive loading (RB). Buthionine sulfoximine (BSO) lowers tissue GSH by irreversibly inhibiting the rate-limiting synthesis enzyme γ- glutamylcysteine synthetase. We investigated the effects of BSO on rat diaphragm function both at rest and after a period of RB. Rats in the RB groups underwent inspiratory RB until they were unable to sustain 70% of their maximal airway pressure. A portion of the diaphragm was analyzed for GSH and GSSG levels, and measurements of in vitro contractile properties included contraction times, maximal tetanic tension (Po), maximal twitch tension (Pt), and force frequency curves. BSO treatment produced a profound depletion of diaphragmatic GSH. Neither BSO nor RB alone significantly altered diaphragm contractile properties at this load of RB. But, in BSO-RB rats, there was a significant decrease in Pt, Po, and tetanic tension at all frequencies of stimulation compared with those in other groups. These data reveal that animals treated with BSO followed by inspiratory resistive loading exhibit marked diaphragm impairment, suggesting that GSH may play an important role in protecting the diaphragm from the stress induced by this resistive breathing protocol.
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U2 - 10.1164/ajrccm.149.4.7908245
DO - 10.1164/ajrccm.149.4.7908245
M3 - Article
C2 - 7908245
AN - SCOPUS:0028286850
SN - 1073-449X
VL - 149
SP - 915
EP - 919
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 4
ER -