Hepatic and splanchnic nitric oxide activity in patients with cirrhosis

Background-In animal models of cirrhosis, altered activity of nitric oxide (NO) has been implicated in the pathogenesis of increased intrahepatic port al vascular resistance and abnormal mesenteric vasodilatation. Aims-To investigate NO activity in the liver and splanchnic vascular bed of patients with cirrhosis. Methods-Activity of the calcium dependent constitutive and calcium independ ent inducible isoforms of NO synthase (cNOS and iNOS, respectively) was ass ayed biochemically in biopsy specimens of liver and a vascular portion of t he greater omentum (representative of mesenteric vasculature) obtained from patients with cirrhosis undergoing liver transplantation (n=14) and non-ci rrhotic control patients undergoing liver resection for metastases (n=9). T he concentration of NO metabolites (NO2 + NO3) in portal and peripheral ven ous plasma was measured. Results-The activity of cNOS was lower in cirrhotic compared with non-cirrh otic subjects for both liver and omentum. Hepatic and omental iNOS activiti es did not differ significantly between the two groups. Portal (NO2 + NO3) was threefold higher in cirrhotic than non-cirrhotic patients, but no diffe rences were observed in systemic venous samples from the two groups. Conclusions-The activity of cNOS is diminished in the cirrhotic human liver . The resultant decrease in constitutive NO release may promote an increase in the intrahepatic portal vascular resistance. Elevated portal venous (NO 2 + NO3) indicates enhanced splanchnic vascular release of NO in cirrhotic patients, but the absence of increased NOS activity in the mesenteric vascu lature suggests differential regulation of NO synthesis within the splanchn ic vascular bed.