Cooperation of Liver Cells in the Regulation of Sinusoidal Contractility

Abstract

The regulation of sinusoidal blood flow and intrahepatic vascular resistance in normal and damaged liver has been the subject of intensive studies aimed at the elucidation of the pathogenesis of portal hypertension, a life-threatening complication of liver fibrosis and cirrhosis. Apart from regulatory mechanisms operating at the level of pre- and postcapillary vessels, it was shown in vivo that sinusoids constrict in a graded and reversible manner in response to specific mediators acting on hepatic stellate cells both under normal and pathological conditions (Clemens and Zhang 1999). Hepatic stellate cells have a strategic position in the perisinusoidal space and their long cytoplasmic processes, containing vast numbers of microfilaments, embrace endothelial cells (Fig. 3). Moreover, processes of stellate cells were found to be in the vicinity of nerve endings (Bioulac-Sage et al. 1990; Tiniakos et al. 1996; Ueno and Tanikawa 1997). In vitro nonactivated quiescent HSC do not contract (Kawada et al. 1992); however, contraction of activated stellate cells in culture mediated by increase in intracellular calcium concentration (Oide et al. 1999) can be directly quantified (Thimgan and Yee 1999).