Nitric oxide and cirrhosis of the liver

A major characteristic of patients with liver cirrhosis is a marked periphe ral and splanchnic vasodilatation that is the origin of many clinical probl ems associated with chronic liver damage, such as water and sodium retentio n, ascites and renal failure. There are several lines of evidence suggestin g a role for nitric oxide (NO), a gaseous substance with potent vasodilator effects, in the peripheral vasodilatation associated with hepatic cirrhosi s. In experimental models of cirrhosis in rats, most studies have reported an increased NO release by the endothelium of different arteries, which pre cedes the develop ment of the systemic hyperdynamic circulation. In additio n, the endothelium-derived increased product ion of NO seems to be responsi ble for the lower than normal pressor response to vasoconstrictors in the m esenteric bed, kidney and in aortic rings of cirrhotic rats. The hyperdynam ic circulation is partially reversed by NO synthesis inhibition. Thus, in e xperimental models of cirrhosis, most studies suggest a primary role of NO in the pathogenesis of the arterial vasodilatation. In humans, studies are scarce and not so homogeneous. Although there are some studies showing incr eased plasma NO levels in cirrhotic patients, there is not full agreement o n the role of increased NO production in the maintenance of peripheral vaso dilatation. Thus, despite some contradictory results, we can conclude that an increased production of NO, mainly of constitutive and endothelial origi n, is an important factor that contributes to the cardiovascular and renal alterations observed in cirrhotic patients or in experimental models of liv er cirrhosis. Whether this enhanced production of NO is the cause of these alterations or a secondary effect in compensation to the elevated levels of the vasoconstrictor and antinatriuretic hormones is not yet known.