Elevated nitric oxide levels in patients with chronic liver disease and cirrhosis correlate with disease stage and parameters of hyperdynamic circulation

Abstract

Chronic liver diseases are accompanied by changes in splanchnic and systemic circulation. These changes are characterised by a reduction in peripheral vascular resistance and an increased cardiac output at rest. An increased release of nitric oxide (NO) has been proposed to play a role in the pathogenesis of vasodilatation and vascular hypocontractility. This study was designed to determine the nitric oxide metabolism measured as circulating nitrate levels in serum/urine in patients with chronic liver disease and cirrhosis. The nitrate concentrations were significantly increased in advanced degrees in cirrhosis Child B and C, and normal or even reduced in patients with chronic active hepatitis and early cirrhosis. In our study the connections between the extent of portal hypertension and nitrate levels were evident. The presence of ascites as well as the the progression of oesophageal varices were associated with higher circulating nitrate levels. The connection between increased nitric oxide production and the haemodynamic sequelae of portal hypertension is also apparent in the significant correlation between plasma renin and serum nitrate levels. Circulating nitrate levels also correlated to the serum interleukin-6 levels. This study demonstrated that the increased nitric oxide metabolism is associated with the haemodynamic alterations induced by portal hypertension.