Effects of ethanol on L-arginine transport in rat Ito cells in relation tonitric oxide production

Background: Nitric oxide (NO) is a potent mediator of hepatic sinusoidal he modynamics that is synthesized in the hepatic stellate cells (Ito cells, fa t-storing cells) and affects these cells. NO production may depend on the i nduction of inducible nitric oxide synthase and on transport of extracellul ar L-arginine. The precise mechanism that controls NO production in stellat e cells was characterized recently. Methods: Kinetic analysis of L-arginine transport and reverse transcription -polymerase chain reaction for cationic amino acid transporter (CAT) were c arried out by using stellate cells prepared from the male Wistar rat. The e ffect of ethanol on L-arginine transport and NO production of stellate cell s was assessed in the presence of tumor necrosis factor (TNF)-alpha and int erferon (IFN)-gamma Results: The L-arginine transport system functioning in the hepatic stellat e cells was system y+, possibly mediated by CAT-1 and CAT-2B (K-m similar t o 50 muM). IFN-gamma in combination with TNF-alpha induced NO production wi th an enhancement in CAT-2B mRNA expression and L-arginine transport, where as L-arginine transport and NO production were suppressed by coincubated et hanol. Conclusions: In hepatic stellate cells, ethanol has suppressive effects on NO production and extracellular L-arginine transport in the presence of TNF -alpha and IFN-gamma. The estimated K,of L-arginine transporter in hepatic stellate cells is very similar to the physiological L-arginine concentratio n in portal vein. Our findings may support the merit of further studies on the modulation of NO production via access to portal blood L-arginine conce ntration to control disturbed hepatic sinusoidal blood flow in patients wit h alcoholic liver disease.