Inhibition of nitric oxide synthesis in ischemia/reperfusion of the rat liver is followed by impairment of hepatic microvascular blood flow

Background: Recent studies provide evidence that nitric oxide (NO) has beneficial effects in hepatic ischemia/reperfusion injury The purpose of this study was to evaluate whether nitric oxide is involved in the regulation of hepatic microvascular perfusion after warm hepatic ischemia, Therefore, we performed a study using in vivo fluorescence microscopy, Methods: Clamping of the left liver lobe was performed in male Wistar rats for the duration of 70 min, One experimental group (n=8) received L-NAME (N-W-nitro-L-arginine methyl ester hydrochloride), an NO-synthase inhibitor, 1 min prior to reperfusion, A second experimental group (n=8) received L-arginine (NO-substrate) continuously infused throughout the observation period, Controls (n=8) received equivalent volumes of an isotonic solution and underwent the same procedures, Hepatic microvascular blood flow and leukocyte-endothelial cell interaction was studied between 20 and 90 min after reperfusion using in vivo fluorescence microscopy. Results: Inhibition of NO-synthesis during reperfusion by application of L-NAME caused a marked decrease in sinusoidal blood how velocity, Furthermore, we noted an increase of non-perfused sinusoids in this group, Treatment with L-arginine improved functional perfusion of hepatic acini and reduced significantly the number of adherent leukocytes in sinusoids and venules compared to control animals, Conclusions: Our results provide further evidence that NO maintains postischemic hepatic microvascular perfusion and that inhibition of NO synthesis has detrimental effects on hepatic microhemodynamics during reperfusion.