Nitric oxide and portal hypertension.

In liver cirrhosis, an increase in hepatic resistance is the initial phenomenon leading to portal hypertension. This is primarily due to the structural distortion of the intrahepatic microcirculation caused by cirrhosis. However, similar to other vascular conditions, architectural changes in the liver are associated with a deficient nitric oxide (NO) production, which results in an increased vascular tone with a further increase in hepatic resistance and portal pressure. New therapeutic strategies are being developed to selectively provide the liver with NO, overcoming the deleterious effects of systemic vasodilators. On the other hand, a strikingly opposite process occurs in splanchnic arterial circulation, where NO production is increased. This results in splanchnic vasodilatation and subsequent increase in portal inflow, which contributes to portal hypertension. Systemic blockade of NO in portal hypertension attenuates the hyperdynamic circulation, but its effects increasing hepatic resistance may offset the benefit of reducing portal inflow, thus preventing an effective reduction of portal pressure. Moreover, it cannot be ruled out that NO blockade may have a deleterious action on cirrhosis progression, which raises caution about their use in patients with cirrhosis.