Inhibition of nitric oxide formation in vivo enhances superoxide release by the perfused liver.
Nitric oxide, a known scavenger of toxic oxygen-derived radicals, has been shown to have a protective effect against tissue injury in endotoxemia. Based on the hypothesis that under normal physiological conditions, a balance between superoxide and nitric oxide exists in vivo, this work examines hepatic superoxide release after nitric oxide formation is inhibited in vivo. Male Sprague-Dawley rats were treated intravenously with N omega-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg body wt), an inhibitor of nitric oxide synthase. One hour later, superoxide anion release by the perfused liver was determined. Results show that a significant amount of superoxide was released after L-NAME treatment. Likely sources of this radical are the Kupffer cells. Inhibition of nitric oxide formation in vivo did not enhance superoxide release by hepatocytes or sinusoidal endothelial cells. The effect of L-NAME treatment on superoxide release in endotoxemic rats was also examined 12 h after lipopolysaccharide treatment, when toxic oxygen-derived radical formation could not be detected. Inhibition of nitric oxide release in vivo in these rats enhanced the formation of superoxide anion. The interaction between nitric oxide and superoxide anion under normal conditions may represent an important protective mechanism of the host against free radical damage.
Bautista
A P
AP
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Spitzer
J J
JJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism*; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D015054:Zymosan / Q000494:pharmacology
D003574:Cytochrome c Group; D013481:Superoxides; D009569:Nitric Oxide; D015054:Zymosan; D001120:Arginine; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate; D019331:NG-Nitroarginine Methyl Ester