Abstract: The cell biology and an understanding of the pathogenesis of portal hypertension has evolved substantially over the last two decades, and is complex, involving cells and molecules both within the liver (intrahepatic) and outside of the liver (extrahepatic). Hepatic cells involved in intrahepatic portal hypertension include endothelial cells and stellate cells. Stellate cell contractility has been the subject of considerable interest because their perisinusoidal constriction appears to be a mechanism of blood flow regulation; in liver injury, enhanced constriction causes an increase in intrahepatic resistance. Vasoactive mediators have important effects on stellate cells; endothelin-1 and nitric oxide are the most prominent mediators. The effects of these vascular mediators on stellate cells are important not only because they modulate intrahepatic resistance, but also because they modulate fibrogenesis—endothelin in particular. Thus, an important underlying theme concerning vascular mediators in liver disease is that they play dual roles—in portal hypertension and in fibrogenesis. Abundant pre-clinical data suggest that strategies focused on the effects of vasoactive compounds on stellate cells will be useful for the treatment of portal hypertension and fibrosing liver disease. Importantly, however, because of systemic hemodynamic abnormalities in cirrhotics and potential adverse effects of vasoactive compounds in the peripheral vasculature, the best therapeutic agents would be expected to be liver specific.
Publication Year: 2015
Publication Date: 2015-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
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Cited By Count: 3
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