Hepatic Innervation and Hepatic Sinusoidal Cells

The innervation of the human liver is distributed throughout the hepatic lobules from the portal spaces to the centralobular spaces. Nerve endings in the intralobular spaces are localized mainly in the Disse spaces, and are closely related to hepatic stellate cells (HSCs). Various neurotransmitters such as substance P exist in these nerve endings. Substance P induces contraction in HSCs. In addition, HSCs possess endothelin (ET) receptors, and contract in response to ET-1 treatment. Moreover, α-smooth muscle actin (α-SMA) is localized in the cytoplasm of HSCs. α-SMA is closely related to the contractility of smooth muscle cells. Nitric oxide (NO) inhibits the contraction of HSCs. HSCs thus appear to be involved in the regulation of hepatic sinusoidal microcirculation by contraction and relaxation. In the human cirrhotic liver, intralobular innervation is decreased or absent, but ET, ET receptors, and NO are overexpressed in the HSCs. These phenomena indicate that HSCs in the human cirrhotic liver may play an important role in the sinusoidal microcirculation through agents such as ET or NO rather than through intralobular innervation.