AIM: To assess whether a liver specific nitric oxide (NO)donor (V-PYRRO/NO) would prevent the development of portal hypertension and liver fibrosis in rats with bile duct ligation (BDL).METHODS: Treatment (placebo or V-PYRRO/NO0.53 μmol/kg per hour) was administered i.v. to rats 2 d before BDL (D-2) and maintained until the day of hemodynamic measurement (D26). Intra-hepatic NO level was estimated by measuring liver cGMP level. Effects of V-PYRRO/NO on liver fibrosis and lipid peroxidation were also assessed.RESULTS: Compared to placebo treatment, V-PYRRO/NO improved splanchnic hemodynamics in BDL rats:portal pressure was significantly reduced by 27% (P＜ 0.0001) and collateral circulation development was almost completely blocked (splenorenal shunt blood flow by 74%, P = 0.007). Moreover, V-PYRRO/NO significantly prevented liver fibrosis development in BDL rats (by 30% in hepatic hydroxyproline content and 31% in the area of fibrosis, P ＜ 0.0001 respectively), this effect being probably due to a decrease in lipid peroxidation by 44% in the hepatic malondialdehyde level (P =0.007). Interestingly, we observed a significant and expected increase in liver cGMP, without any systemic hemodynamic effects (mean arterial pressure, vascular systemic resistance and cardiac output) in both shamoperated and BDL rats treated with V-PYRRO/NO. This result is in accordance with studies on V-PYRRO/NOmetabolism showing a specific release of NO in the liver.CONCLUSION: Continuous administrations of V-PYRRO/NO in BDL rats improved liver fibrosis and splanchnic hemodynamics without any noxious systemic hemodynamic effects.