The role of endothelin-1 and its receptor blockers on the liver function.

Endothelin-1 (ET-1) was first described by Yanagisawa et al. (1988) as a 21-amino acid peptide present in the extract from the aorta endothelial cells. It is known that ET-1 is one of the most potent vasoconstrictor compounds and also causes proliferation of many of the vascular cells involved in vascular remodeling. This peptide exerts its action through interactions with its membrane receptors - ETA and ETB. These receptors are expressed in the vascular smooth muscle cells, endothelial cells, intestines and the brain. Secretion of ET-1 results in long-lasting vasoconstriction, increased blood pressure and, in turn, overproduction of free radicals. As dysregulation of the endothelin system is an important factor in the pathogenesis of several diseases including atherosclerosis, hypertension and endotoxic shock, the ETA and ETB receptors are attractive therapeutic targets for treatment of these disorders. Recently, several clinical trials have provided evidence that ET-1 receptor antagonism influences liver function and has therapeutic potential in the treatment of liver impairment. Therefore, this review summarizes recent clinical trials on the role of ET-1 receptor blockers with respect to the modulation of liver function.