Pharmacological Effects of Estrogen in Liver Cirrhosis-Induced Portal Hypertension

In the livers of humans, cats, and guinea pigs, nerve endings are distributed all over the hepatic lobules. Nerve endings in the intralobular spaces are localized mainly in the Disse spaces, and are oriented towards the hepatic stellate cells (HSCs), sinusoidal endothelial cells (SECs) and hepatocytes. They are especially closely related to HSCs. Various neurotransmitters such as substance P (SP) exist in the nerve endings. In addition, HSCs possess endothelin (ET) and adrenergic receptors, and contract in response to the corresponding agonists. In contrast, 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 cirrhotic liver, intralobular innervation is decreased, but NO is overexpressed in the SECs. These findings indicate that the sinusoidal microcirculation through NO rather than through intralobular innervation may be involved in cirrhotic liver. Moreover, estrogen plays an important role in the enhancement of NO production in the SECs of cirrhotic liver and reduces the portal pressure

Keywords: Liver cirrhosis, portal hypertension, estrogen, 17β-estradiol, vascular tone, hepatic stellate cells, hepatic sinusoidal endothelial cells, neurotransmitters, substance P, endothelin, nitric oxide, hepatic blood flow, portal venous pressure