摘要
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/NO 0.53 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 sham- operated and BDL rats treated with V-PYRRO/NO. This result is in accordance with studies on V-PYRRO/NO metabolism showing a specific release of NO in the liver.NO in BDL rats improved liver fibrosis and splanchnic hemodynamics without any noxious systemic hemo- dynamic effects.
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/NO 0.53 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/NO metabolism showing a specific release of NO in the liver.NO in BDL rats improved liver fibrosis and splanchnic hemodynamics without any noxious systemic hemodynamic effects.
