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Endothelin may be involved in many of the vascular abnormalities in patients with cirrhosis, and its overall effects in different tissues may depend on differential expression of endothelin receptors on smooth muscle and endothelial cells
Many of the complications of cirrhosis result from haemodynamic changes involving the systemic circulation and regional vascular beds. Typically, patients with advanced cirrhosis and portal hypertension have a hyperdynamic vasodilated circulation characterised by high cardiac output and low blood pressure, and this leads to compensatory activation of vasoconstrictor systems, including the sympathetic nervous system and renin-angiotensin-aldosterone systems.1 Much of this picture can be attributed to vasodilatation of the mesenteric vascular bed which in turn contributes to portal hypertension by increasing portal inflow. While vascular resistance in the mesenteric bed is reduced, another major contributor to portal hypertension is an increase in vascular tone within the liver which is at least partly mediated by hepatic stellate cells. Altered local vascular tone contributes to other important complications of cirrhosis—intrarenal vasoconstriction can result in the hepatorenal syndrome, while in the lung pathological vasodilatation can result in the development of the hepatopulmonary syndrome, and less commonly pulmonary vasoconstriction may result in portopulmonary hypertension. As a result there has been intense interest in understanding the mechanisms and vascular mediators responsible for these systemic and regional changes in vascular tone with the hope that this will lead to the development of new treatments.
Endothelin 1 (ET-1) is a potent endothelium derived vasoactive peptide that plays a central role in regulating vascular tone in healthy individuals but has multiple other actions that may be of importance in disease, including stimulation of cellular growth and proliferation, and involvement in the wound healing response and tissue fibrogenesis.2,3 For more than a decade there has been major interest in the possible role …
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