Exogenous and endogenous nitric oxide but not iNOS inhibition improves function and survival of ischemically injured livers

The role of nitric oxide (NO) in liver ischemia/reperfusion (I/R) injury re mains controversial and few works have shed more information regarding the effect of exogenous (EX) and/or endogenous NO (EN) under conditions of I/R of the liver. We investigated the role of exogenous and endogenous NO and i nducible nitric oxide synthase (iNOS) inhibition in liver function, neutrop hil infiltration, and animal survival after liver I/R. Sprague-Dawley rats were subjected to total hepatic ischemia for 90 min using an extracorporeal porto-systemic shunt. The animals were divided into five groups, including the sham porto-systemic shunt with no ischemia, the control ischemic group , the L-arginine-treated group, the sodium nitroprusside (SNP or NaNP)-trea ted group, and the L-N-6-(1-iminoethyl) lysine hydrochloride (L-NIL) (selec tive iNOS inhibitor)-treated group. The animal survival was followed for 7 days. Liver injury tests, tissue myeloperoxidase (MPO), and histology were analyzed at 6 h postreperfusion. L-Arginine- and sodium nitroprusside-treat ed groups demonstrated significant improvement in 7 days survival in compar ison to the control (20%) ( p <. 05). The best overall survival was obtaine d with SNP (70%), followed by survival in the L-arginine treated group (60% ). The iNOS inhibitor group (40%) did not show any statistical significance when compared to the control group ( p >.05). Liver injury tests and histo logy scores in the SNP- and L-arginine-treated groups showed significant im provement when compared to the control group ( p <.01 and p <.05, respectiv ely). The iNOS group demonstrated only a slight improvement in these parame ters. The liver MPO (as a measurement of neutrophil migration into the live r parenchyma) was significantly decreased only in the SNP and L-arginine gr oups ( p <.05) but not in the iNOS group ( p >.5). We conclude that NO exog enous donors and substrates for the endogenous pathway are beneficial for t he liver after severe I/R and could be important therapeutic targets to pre vent damage following this phenomenon.