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.