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 endoto xemia. Based on the hypothesis that under normal physiological conditi ons, a balance between superoxide and nitric oxide exists in vivo, thi s work examines hepatic superoxide release after nitric oxide formatio n is inhibited in vivo. Male Sprague-Dawley rats were treated intraven ously with N omega-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg bod y wt), an inhibitor of nitric oxide synthase. One hour later, superoxi de anion release by the perfused liver was determined. Results show th at a significant amount of superoxide was released after L-NAME treatm ent. Likely sources of this radical are the Kupffer cells. Inhibition of nitric oxide formation in vivo did not enhance superoxide release b y hepatocytes or sinusoidal endothelial cells. The effect of L-NAME tr eatment on superoxide release in endotoxemic rats was also examined 12 h after lipopolysaccharide treatment, when toxic oxygen-derived radic al 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 co nditions may represent an important protective mechanism of the host a gainst free radical damage.