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 isch emia, Therefore, we performed a study using in vivo fluorescence micro scopy, Methods: Clamping of the left liver lobe was performed in male Wistar rats for the duration of 70 min, One experimental group (n=8) r eceived L-NAME (N-W-nitro-L-arginine methyl ester hydrochloride), an N O-synthase inhibitor, 1 min prior to reperfusion, A second experimenta l 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, Hep atic microvascular blood flow and leukocyte-endothelial cell interacti on was studied between 20 and 90 min after reperfusion using in vivo f luorescence microscopy. Results: Inhibition of NO-synthesis during rep erfusion by application of L-NAME caused a marked decrease in sinusoid al blood how velocity, Furthermore, we noted an increase of non-perfus ed sinusoids in this group, Treatment with L-arginine improved functio nal perfusion of hepatic acini and reduced significantly the number of adherent leukocytes in sinusoids and venules compared to control anim als, Conclusions: Our results provide further evidence that NO maintai ns postischemic hepatic microvascular perfusion and that inhibition of NO synthesis has detrimental effects on hepatic microhemodynamics dur ing reperfusion.