INHIBITION OF NITRIC-OXIDE SYNTHESIS AGGRAVATES REPERFUSION INJURY AFTER HEPATIC ISCHEMIA AND ENDOTOXEMIA

The potential role of nitric oxide (NO) was investigated in the pathop hysiology of liver injury after priming with 20 min hepatic ischemia-r eperfusion and administration of .5 mg/kg Salmonella enteritidis endot oxin. Liver injury during the early reperfusion phase of 4 h was chara cterized by severe vascular oxidant stress, lipid peroxidation (LPO), neutrophil infiltration, and a 33% reduction of the microvascular bloo d flow in the liver. Inhibition of NO synthesis with N-omega-nitro-L-a rginine methyl ester hydrochloride (L-NAME) aggravated liver injury by 90%, reduced LPO, and did not affect liver neutrophils but further im paired microvascular blood flow, Treatment with the NO-donor spermine- NONOate or L-arginine did not affect these parameters in postischemic animals, however, treatment did restore ail values of L-NAME-treated a nimals back to disease control levels. These data suggest that endogen ous NO formation is sufficient to limit ischemic liver injury during r eperfusion but inhibition of NO synthesis will result in additional is chemic damage. NO may also be involved in scavenging of superoxide in the vasculature and in inducing LPO.