Increased production of nitric oxide by neutrophils and monocytes from cirrhotic patients with ascites and hyperdynamic circulation

Hepatology. 1995 Dec;22(6):1666-73.


An increased release of nitric oxide (NO), a powerful vasodilating agent, has been proposed to play a role in the pathogenesis of vasodilation and hyperdynamic circulation associated with advanced cirrhosis. We evaluated NO synthase (NOS) activity in peripheral leukocytes of 12 cirrhotic patients and 9 healthy subjects together with plasma endotoxin levels and systemic hemodynamic (by a noninvasive echocardiographic method). NOS activity was evaluated by (1) measuring the capacity of isolated polymorphonuclear cells (PMNs) and monocytes to convert [3H]arginine to [3H]citrulline; (2) measuring the ability of neutrophils and monocytes to inhibit thrombin-induced platelet aggregation and to increase guanosine 3'-5'-cyclic monophosphate content in coincubated platelets, an expression of NO release from these cells. Both neutrophils and monocytes from cirrhotic patients produced significantly higher amounts of [3H]citrulline than cells obtained from healthy subjects (P < .001 and P < .02 for neutrophils and monocytes, respectively) and were more effective than control cells in inhibiting platelet aggregation (P < .05 and P < .001, respectively for 2 x 10(6) cells) and in increasing guanosine 3'-5'-cyclic monophosphate content in coincubated platelets (P < .05 and P < .001, respectively). The anti-aggregating activity expressed by leukocytes has a pharmacological profile similar to that described for NO, because it increased after addition of superoxide dismutase, a superoxide anion scavenger, and markedly decreased after inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine-methyl ester (L-NAME). Cirrhotic patients had significantly higher plasma endotoxin levels (P < .001) and cardiac index (P < .01) when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arginine / metabolism
  • Ascites
  • Blood Platelets / metabolism
  • Citrulline / metabolism
  • Enzyme Inhibitors
  • Female
  • Guanosine Monophosphate / blood
  • Heart Rate
  • Humans
  • Lipopolysaccharides / pharmacology
  • Liver Cirrhosis / blood*
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Neutrophils / metabolism*
  • Nitric Oxide / blood*
  • Nitric Oxide / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / blood
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors / pharmacology
  • Stroke Volume
  • Tritium


  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Platelet Aggregation Inhibitors
  • Tritium
  • Citrulline
  • Nitric Oxide
  • Guanosine Monophosphate
  • Arginine
  • Nitric Oxide Synthase