HEPATOLOGY Concise Review sion. 1 Their precise site of action is controversial but in The Cellular Pathogenesis of theory could be at any of several levels within the liver, including presinusoidal, sinusoidal, or postsinusoidal. [2][3][4] Portal Hypertension: Stellate A recent development in the field is the realization that sinusoidal flow may be regulated by stellate cells (also Cell Contractility, Endothelin, known as lipocytes, Ito, or perisinusoidal cells), mesen- chymal cells that reside in the perisinusoidal space of and Nitric Oxide Disse. Two vasoregulatory compounds with evident effects on this cell include endothelin (ET) and nitric oxide DON ROCKEY (NO). This review will consider the respective roles of stellate cells, ET, and NO in intrahepatic vasoregulation and the implications for treatment of portal hyperten-A number of vasoactive substances have been advanced as potential mediators of intrahepatic portal hyperten-sion. FIG. 1. Endothelin biology in the liver. Endothelins are produced largely in endothelial cells by cleavage of prepro molecules to big endothelin and then to the mature peptide(s) of 21 amino acid residues. The mature peptides act either in a paracrine manner (i.e., in liver on stellate cells or in the vasculature on local smooth muscle cells) or on endothelial cells themselves. This figure draws on data from both liver and nonliver sources (see text). In liver injury, both endothelial cells and stellate cells (broken arrow) are potential sources of ET. TNFa, tumor necrosis factor a; IF, interferon; LPS, lipopolysaccharide; PKC, protein kinase C; DAG, diacylglycerol; IP3, inositol triphosphate.