Vascular mediators in the injured liver

Abstract

Vasoactive mediators have important effects on sinusoidal cells (endothelial and stellate) and are important not only because they modulate intrahepatic resistance, but also because they modulate fibrogenesis (and it is likely that other critical roles for these mediators will emerge). Endothelin, angiotensin, and NO are currently the most attractive therapeutic targets. Recent preclinical data suggest that strategies focused on these compounds in the treatment of portal hypertension and fibrosing liver disease will soon emerge. An important underlying theme concerning vascular mediators in liver disease is that they play dual roles: in portal hypertension and in fibrogenesis. A critical caveat in targeting vascular systems in patients with advanced chronic liver disease, and particularly those with portal hypertension, is that vasoactive compounds, antagonists, or synthesis inhibitors will almost certainly have significant systemic hemodynamic effects. Therefore, ideal therapeutic agents will need to be targeted specifically to the liver.