Hemodynamic and antifibrotic effects of a selective liver nitric oxide donor V-PYRRO/NO in bile duct ligated rats.

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 micromol/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.

• Authors: 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
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 12 Issue 41 Pg. 6639-45 (Nov 07 2006) ISSN: 1007-9327 [Print] United States
• PMID: 17075977 (Publication Type: Journal Article)

Chemical References

• Nitric Oxide Donors
• O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate
• Pyrrolidines
• Nitric Oxide
• Aspartate Aminotransferases
• Alkaline Phosphatase
• Bilirubin

Topics

• Alkaline Phosphatase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Bile Ducts (physiopathology)
• Bilirubin (blood)
• Blood Pressure (drug effects)
• Disease Models, Animal
• Heart Rate (drug effects)
• Hypertension, Portal (etiology, prevention & control)
• Ligation
• Lipid Peroxidation (drug effects)
• Liver Circulation (drug effects)
• Liver Cirrhosis (etiology, prevention & control)
• Male
• Nitric Oxide (blood)
• Nitric Oxide Donors (pharmacology)
• Pyrrolidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Vascular Resistance (drug effects)