Endothelin-Induced Contraction of the Portal Vein in Cirrhosis

Endothelin (ET) is one of the most potent vasoconstrictors known so far. It has been proposed that the ET-induced contraction of hepatic stellate cells (Ito, endothelial cells) is an important mechanism for the development of portal hypertension. The purpose of this study was to investigate in an in vitro model whether ET causes a contraction of the portal vein which can contribute to portal hypertension in cirrhosis. Portal veins from normal and cirrhotic rats were used for experiments. Measurements were performed in vitro for cumulative concentrations of ET-1 and ET-3 (1, 5, 10, 50 and 100 nM). Both ETs caused a dose-dependent increase in portal venous tension; the maximal tension (Tmax) was measured at 50 nM. The measured Tmax was higher for cirrhotic (ET-1: Tmax = 189%; ET-3: Tmax = 175%) than for normal rats (ET-1: Tmax = 130%; ET-3: Tmax = 151%). ET-3 produced a higher tension of portal veins in normal rats than ET-1. In conclusion, this study shows that portal veins from cirrhotic rats react more sensitively to ET than those from normal rats. Besides the ET-induced contraction of hepatic stellate cells, contraction of the portal vein and its intrahepatic branches, especially in cirrhotic individuals, has to be considered as a further mechanism of ET contributing to portal hypertension.