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 cell s (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 c ontribute to portal hypertension in cirrhosis. Portal veins from normal and cirrhotic rats were used for experiments, Measurements were performed in v itro for cumulative concentrations of ET-1 and ET-3 (1, 5, 10, 50 and 100 n M). Both ETs caused a dose-dependent increase in portal venous tension; the maximal tension (T-max) was measured at 50 nM. The measured T-max was high er for cirrhotic (ET-1: T-max = 189%; ET-3: T-max = 175%) than for normal r ats (ET-1: T-max = 130%; ET-3: T-max = 151%). ET-3 produced a higher tensio n 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 th ose from normal rats. Besides the ET-induced contraction of hepatic stellat e cells, contraction of the portal vein and its intrahepatic branches, espe cially in cirrhotic individuals, has to be considered as a further mechanis m of ET contributing to portal hypertension.