Prevention of portal hypertension and portosystemic shunts by early chronic administration of clonidine in conscious portal vein-stenosed rats

The hemodynamic effects, including mesentericsystemic shunts of early chronic administration of clonidine, were studied in conscious, unrestrained, portal vein-stenosed rats. In rats receiving early chronic clonidine (600 μg · kg⁻¹ · day⁻¹ by gavage), begun 3 days before portal vein stenosis and then administered continuously for 10 consecutive days, portal pressure (10.0 ± 1.5 mm Hg) and degree of mesenteric-systemic shunts (58% ± 25%) were significantly lower than in the placebo group (15.2 ± 1.5 mm Hg and 83% ± 7%, respectively). The effects were observed either 2 to 3 hr or 18 to 24 hr after the last dose of clonidine. In rats receiving clonidine continuously for 5 days, starting 5 days after portal vein stenosis, portal pressure (11.0 ± 1.3 mm Hg) was significantly lower than in the placebo group, but mesenteric-systemic shunts (82% ± 8%) were not significantly different. In rats receiving a single oral dose of clonidine (600 μg/kg) 10 days after portal vein stenosis, portal pressure (11.8 ± 2.1 mm Hg), measured 2 to 3 hr after clonidine administration, was significantly lower than in the placebo group. Mesenteric-systemic shunts (83% ± 8%), however, were not significantly different from the placebo group. In addition, 18 to 24 hr after a single dose of clonidine, hemodynamic values returned to basal conditions. We also demonstrated that chronic clonidine administration begun before portal vein stenosis can reduce the initial increase in portal pressure after this procedure. We concluded that early chronic clonidine administration reduces the severity of portal hypertension and the development of portosystemic shunts in portal vein-stenosed rats. These beneficial effects are probably due to a limitation of the initial increase in portal pressure that follows portal vein stenosis (HEPATOLOGY 1991;14:325–330.)