Effects of L-NAME and L-arginine on diaphragm contraction in a septic animal model.
The effects of nitric oxide on diaphragm contraction after endotoxin administration were studied in Wistar rats. The animals were divided into seven treatments: a saline-injected group as control, three groups injected with L-NAME (0.01, 0.1, 1 mg/kg) and three groups injected with L-arginine (1, 10, 100 mg/kg). Escherichia coli endotoxin was injected into the peritoneal cavity 15 min later. Twitch kinetics and force-frequency curves were measured 0, 2, and 4 hr after endotoxin injection. In the control group, the force-frequency curves significantly decreased from 0 hr to 4 hr. In the L-NAME group, the force-frequency curves at 4 hr showed significant increases in a dose-dependent manner. In the L-arginine group, the force-frequency curve with 100 mg/kg at 4 hr showed a significant increase. There was no consistent change in the contraction time, half relaxation time, or fatiguability. NADPH diaphorase histochemistry performed on diaphragm muscle samples 4 hr after endotoxin injection showed positive in the control and L-arginine group, but was only weakly observed in L-NAME group. These data suggest that nitric oxide contributes to the endotoxin induced diaphragm contractile deterioration.
The First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan. cshindoh@mail.cc.tohoku.ac.jp
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Shindoh
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Wu
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Ohuchi
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Kurosawa
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Kikuchi
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Hida
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Shirato
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology*; D004731:Endotoxins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli; D006651:Histocytochemistry; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D018763:Muscle Fatigue / Q000187:drug effects; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D004731:Endotoxins; D004791:Enzyme Inhibitors; D001120:Arginine; D009252:NADPH Dehydrogenase; D019331:NG-Nitroarginine Methyl Ester