Local regulators of hepatic sinusoidal microcirculation: recent advances

This article reviews our recent studies on the local regulation of hepatic microcirculation with special reference to the inlet sphincter-like structures, the roles of sinusoidal endothelial cells and the mechanism of dynamic changes in the sinusoidal endothelial fenestrae (SEF) as well as in the terminal portal venules and the terminal hepatic arterioles induced by the potent vasoconstrictor endothelin (ET)-1. There are two types of sphincter-like structures at the entering sites of hepatic sinusoids. One is located at the junction between the terminal portal venule and the sinusoid, and is characterized by the large endothelial cells surrounded with Ito cells (hepatic stellate cells: HSCs). The other is located at the junction between the terminal hepatic arteriole and the sinusoid, and corresponds to the precapillary sphincter since our enzymohistochemical demonstration of arterial capillaries in close association with the sinusoids combined with intravital microscopy has revealed that the terminal hepatic arteriole directly terminates in the sinusoid. It is essential for the local control of hepatic sinusoidal blood flow that the dynamic contracting and relaxing changes not only in these inlet sphincter-like structures but also in the SEF correspond with those of the HSCs, both of which are mediated by the sinusoidal endothelium-derived vasoconstrictor endothelins (ETs) and vasodilator nitric oxide (NO). The contractility of the SEF and HSCs depends on the intracellular Ca++-calmodulin-actomyosin system.