title: Resveratrol improves intrahepatic endothelial dysfunction and reduces hepatic fibrosis and portal pressure in cirrhotic rats.
abstract: OBJECTIVE
  Resveratrol, a polyphenol found in a variety of fruits, exerts a wide range of beneficial effects on the endothelium, regulates multiple vasoactive substances and decreases oxidative stress, factors involved in the pathophysiology of portal hypertension. Our study aimed at evaluating the effects of resveratrol on hepatic and systemic hemodynamics, hepatic endothelial dysfunction, and hepatic fibrosis in CCl₄ cirrhotic rats.
  
  
  METHODS
  Resveratrol (10 and 20 mg/kg/day) or its vehicle was administered to cirrhotic rats for two weeks and hepatic and systemic hemodynamics were measured. Moreover, we evaluated endothelial function by dose-relaxation curves to acetylcholine, hepatic NO bioavailability and TXA2 production. We also evaluated liver fibrosis by Sirius Red staining of liver sections, collagen-1, NFκB, TGFβ mRNA expression, and desmin and α-smooth muscle actin (α-SMA) protein expression, as a surrogate of hepatic stellate cell activation.
  
  
  RESULTS
  Resveratrol administration significantly decreased portal pressure compared to vehicle (12.1 ± 0.9 vs. 14.3 ± 2.2 mmHg; p <0.05) without significant changes in systemic hemodynamics. Reduction in portal pressure was associated with an improved vasodilatory response to acetylcholine, with decreased TXA2 production, increased endothelial NO, and with a significant reduction in liver fibrosis. The decrease in hepatic fibrosis was associated with a reduced collagen-1, TGFβ, NFκB mRNA expression and desmin and α-SMA protein expression.
  
  
  CONCLUSIONS
  Resveratrol administration reduces portal pressure, hepatic stellate cell activation and liver fibrosis, and improves hepatic endothelial dysfunction in cirrhotic rats, suggesting it may be a useful dietary supplement in the treatment of portal hypertension in patients with cirrhosis.
authors.affiliation: Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer and Ciberehd, University of Barcelona, Spain.
authors.forename: Marco
authors.initials: M
authors.lastname: Di Pascoli
authors.forename: Marta
authors.initials: M
authors.lastname: Diví
authors.forename: Aina
authors.initials: A
authors.lastname: Rodríguez-Vilarrupla
authors.forename: Eugenio
authors.initials: E
authors.lastname: Rosado
authors.forename: Jorge
authors.initials: J
authors.lastname: Gracia-Sancho
authors.forename: Marina
authors.initials: M
authors.lastname: Vilaseca
authors.forename: Jaume
authors.initials: J
authors.lastname: Bosch
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: García-Pagán
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002251:Carbon Tetrachloride / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006975:Hypertension, Portal / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017082:Portal Pressure / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D013928:Thromboxane A2 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D013928:Thromboxane A2; D002251:Carbon Tetrachloride; D052250:Nitric Oxide Synthase Type III; D000077185:Resveratrol