Anti-inflammatory role of NO in hepatic ischemia-reperfusion in rats I. NO downregulates P-selectin and ICAM-1 gene expression

NO has pro- and anti-inflammatory effects. In the present study, a rat model of hepatic ischemia-reperfusion (I/R) was used to examine the anti-inflammatory role of NO. The left and median lobes of the liver were subjected to 30 min of ischemia by clamping the relevant artery, followed by a 4 h reperfusion achieved by removal of the vascular clamp. The animals were divided into four groups: control; I/R; I/R + L-NAME (10 mg/kg, iv, 10 min prior to reperfusion); and I/R + SNAP (20 μmols/kg, iv, 10 min prior to reperfusion, followed by 12 μmols/kg/h in 1.5 ml saline perfused for 4 h). Results showed that mean arterial blood pressure in I/R + L-NAME rats was higher than in I/R + SNAP rats, but pulse pressure (PP) was lower. Plasma NO₂^- and NO₃^- levels in I/R + SNAP rats were significantly higher when compared with I/R + L-NAME rats. Superoxide generation and ALT activity in ischemic lobes of I/R + L-NAME rats were higher than the rats with SNAP. The ratios of P-selectin and ICAM-1 to GAPDH mRNA extracted from ischemic lobes of I/R with L-NAME were significantly increased when compared with I/R + SNAP group. Results suggest that exogenous or endogenous NO can (1) reduce the vascular tone, increase PP, and improve organ blood perfusion; and (2) decrease P-selectin and ICAM-1 mRNA expression, thereby, reducing PMN-dependent reperfusion tissue injury.