0104: Blackcurrant juice prevents endothelial dysfunction and vascular oxidative stress in the mesenteric artery of cirrhotic rats with hepatopulmonary syndrome

Abstract

The aim of the present study was to determine whether the ingestion of a polyphenol-rich Blackcurrant juice (PRBJ) improves the endothelial dysfunction and vascular oxidative stress in the chronic bile duct ligation (CBDL) rats, an experimental model of hepatopulmonary syndrome (HPS), one of the serious complications of liver cirrhosis. Male Wistar rats received either control drinking water or water containing a 60 mg/kg of PRBJ for 7 weeks. After 3 weeks, the rats underwent either ligation and resection of the common bile duct (CBDL) or sham surgery (sham). Vascular reactivity was assessed in organ chambers, the expression level of proteins by immunofluorescence, and the vascular formation of reactive oxygen species by dihydroethidine. Plasma levels of pro-inflammatory cytokines were evaluated by flow cytometry. Both the nitric oxide (NO)- and the endothelium-dependent hyperpolarization (EDH)-mediated relaxations in mesenteric rings were significantly reduced in CBDL compared to sham. Impaired endothelium-dependent relaxations were associated with a reduced vascular expression of connexin 37 (Cx37) and small conductance calcium-dependent K + channels (SK Ca ), and an increased expression of eNOS. In aortic sections of CBDL, an increased vascular oxidative stress and expression of NADPH oxidase subunits was observed. The endothelial dysfunction in CBDL was significantly prevented by PRBJ, and this effect was associated with the normalization of the vascular expression of Cx37, SK Ca , and eNOS. PRBJ treatment also reduced vascular oxidative stress in the aorta, and the increased plasma level of pro-inflammatory cytokines in CBDL. Altogether, these results indicate that PRBJ ingestion prevented the blunted NO- and EDH-mediated endothelium-dependent relaxation in the mesenteric artery of CBDL most likely by preventing the excessive oxidative stress in the arterial wall.