BACKGROUND: This study was conducted to investigate the effect of chronic bosentan administration on the development of esophageal varices in carbon tetrachloride-induced cirrhosis in rats. METHODS: For the development of liver cirrhosis and esophageal varices, 60 rats underwent ligation of the left adrenal vein, followed by phenobarbital and carbon tetrachloride administration. Two weeks after the beginning of carbon tetrachloride administration, rats were separated into two groups. In group I, comprising 30 rats, bosentan was continuously administered throughout the study, whereas in group II, also 30 rats, placebo instead of bosentan was continuously administered. Hemodynamic studies and morphometric analysis of the lower esophagus were performed after complete induction of cirrhosis. The total number of veins counted in the submucosa, the number of submucosal veins/mm(2) of submucosa, the total submucosal area occupied by vessels, the mean cross-sectional vessel area, the relative submucosal area (percentage) occupied by vessels, and the area of the single most-dilated submucosal vein were studied. RESULTS: Bosentan induced a significant (P < 0.05) decrease in portal pressure, while morphometric analysis revealed a significant reduction (P < 0.05) of all parameters studied in bosentan-treated rats, except in the total and relative number of submucosal veins. CONCLUSIONS: Bosentan administration seemed to significantly attenuate dilation of submucosal veins in the lower esophagus of cirrhotic rats. This effect was mainly attributed to a decrease in the portal pressure induced by chronic bosentan administration.
BACKGROUND: This study was conducted to investigate the effect of chronic bosentan administration on the development of esophageal varices in carbon tetrachloride-induced cirrhosis in rats. METHODS: For the development of liver cirrhosis and esophageal varices, 60 rats underwent ligation of the left adrenal vein, followed by phenobarbital and carbon tetrachloride administration. Two weeks after the beginning of carbon tetrachloride administration, rats were separated into two groups. In group I, comprising 30 rats, bosentan was continuously administered throughout the study, whereas in group II, also 30 rats, placebo instead of bosentan was continuously administered. Hemodynamic studies and morphometric analysis of the lower esophagus were performed after complete induction of cirrhosis. The total number of veins counted in the submucosa, the number of submucosal veins/mm(2) of submucosa, the total submucosal area occupied by vessels, the mean cross-sectional vessel area, the relative submucosal area (percentage) occupied by vessels, and the area of the single most-dilated submucosal vein were studied. RESULTS:Bosentan induced a significant (P < 0.05) decrease in portal pressure, while morphometric analysis revealed a significant reduction (P < 0.05) of all parameters studied in bosentan-treated rats, except in the total and relative number of submucosal veins. CONCLUSIONS:Bosentan administration seemed to significantly attenuate dilation of submucosal veins in the lower esophagus of cirrhotic rats. This effect was mainly attributed to a decrease in the portal pressure induced by chronic bosentan administration.
Authors: S K Sarin; R J Groszmann; P G Mosca; M Rojkind; M J Stadecker; R Bhatnagar; A Reuben; Y Dayal Journal: J Clin Invest Date: 1991-03 Impact factor: 14.808