Nitric oxide and cirrhosis of the liver

A major characteristic of patients with liver cirrhosis is a marked peripheral and splanchnic vasodilatation that is the origin of many clinical problems associated with chronic liver damage, such as water and sodium retention, ascites and renal failure. There are several lines of evidence suggesting a role for nitric oxide (NO), a gaseous substance with potent vasodilator effects, in the peripheral vasodilatation associated with hepatic cirrhosis. In experimental models of cirrhosis in rats, most studies have reported an increased NO release by the endothelium of different arteries, which precedes the development of the systemic hyperdynamic circulation. In addition, the endothelium‐derived increased production of NO seems to be responsible for the lower than normal pressor response to vasoconstrictors in the mesenteric bed, kidney and in aortic rings of cirrhotic rats. The hyperdynamic circulation is partially reversed by NO synthesis inhibition. Thus, in experimental 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 increased plasma NO levels in cirrhotic patients, there is not full agreement on the role of increased NO production in the maintenance of peripheral vasodilatation. Thus, despite some contradictory results, we can conclude that an increased production of NO, mainly of constitutive and endothelial origin, is an important factor that contributes to the cardiovascular and renal alterations observed in cirrhotic patients or in experimental models of liver 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.