INCREASED NITRIC-OXIDE SYNTHESIS AND INDUCIBLE NITRIC-OXIDE SYNTHASE EXPRESSION IN PATIENTS WITH ALCOHOLIC AND NONALCOHOLIC LIVER-CIRRHOSIS

1. The synthesis and release of nitric oxide may play a role in the pa thogenesis of peripheral vasodilatation and hyperdynamic circulation o bserved in liver cirrhosis, In this work, we analysed the synthesis of nitric oxide by the lympho-mononuclear cells of peripheral blood from patients with chronic alcoholic and non-alcoholic liver disease and w e identified the isoform of nitric oxide synthase involved in the incr eased nitric oxide synthesis. 2. Patients were classified following cl inical and histological criteria in non-alcoholic cirrhotic, alcoholic cirrhotic and non-cirrhotic chronic liver disease. We studied clinica l and analytical characteristics, haemodynamic parameters and endotoxi n levels in these patients. 3. Cirrhotic patients showed an increase o f cardiac output and a decrease of peripheral vascular resistance. The se patients had higher levels of plasma endotoxin than those observed in the control group. N-omega-Nitro-L-arginine methyl ester (L-NAME)-i nhibitable nitrite production from mononuclear lymphocyte cells was hi gher in patients than in the control group, the highest levels being i n non-alcoholic cirrhotic patients, and the lowest levels in patients with non-cirrhotic alcoholic liver disease, 4. Immunocytochemistry stu dies revealed a positive immunoreactivity for the inducible isoform of nitric oxide synthase in lympho-mononuclear cells that was more evide nt in non-alcoholic than in alcoholic cirrhotic patients. By Northern blot, inducible nitric oxide synthase mRNA expression was observed onl y in lymphomononuclear cells from non-alcoholic cirrhotic patients. 5. Our patients show a correlation between nitric oxide synthesis, endot oxin levels and haemodynamic parameters. 6. These findings indicate th at lympho-mononuclear cell stimulation may play a role in elevated nit ric oxide production in hepatic cirrhosis, Thus, this increased nitric oxide synthesis could be implicated in the pathogenesis of the haemod ynamic disturbances frequently found in cirrhotic patients. This incre ase seems to be induced, at least in part, by activation of an inducib le isoform of nitric oxide synthase.