Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 7, 2006; 12(41): 6639-6645
Published online Nov 7, 2006. doi: 10.3748/wjg.v12.i41.6639
Hemodynamic and antifibrotic effects of a selective liver nitric oxide donor V-PYRRO/NO in bile duct ligated rats
Frédéric Moal, Nary Veal, Eric Vuillemin, Eric Barrière, Jianhua Wang, Lionel Fizanne, Frédéric Oberti, Olivier Douay, Yves Gallois, Dominique Bonnefont-Rousselot, Marie Christine Rousselet, Paul Calès
Frédéric Moal, Nary Veal, Eric Vuillemin, Eric Barrière, Jianhua Wang, Lionel Fizanne, Marie Christine Rousselet, Paul Calès, Frédéric Obert, Laboratoire HIFIH, UPRES 3859, Université, Angers, France
Olivier Douay, Yves Gallois, Laboratoire de Biochimie, Université, Angers, France
Eric Barrière, INSERM U481, Hôpital Beaujon, Clichy, France
Dominique Bonnefont-Rousselot, Laboratoire de Biochimie, Hôpital de la Salpêtrière, Paris, France
Correspondence to: Paul Calès, MD, Service d’Hépato-Gastroentérologie, CHU, 49033 Angers Cedex 01, France. paul.cales@univ-angers.fr
Telephone: +33-2-41353410 Fax: +33-2-41354119
Received: June 13, 2006
Revised: July 12, 2006
Accepted: September 16, 2006
Published online: November 7, 2006
Abstract

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.

CONCLUSION: Continuous administrations of V-PYRRO/NO in BDL rats improved liver fibrosis and splanchnic hemodynamics without any noxious systemic hemo-dynamic effects.

Keywords: Nitric oxide; Portal hypertension; Liver fibrosis; Hemodynamics; Rats