Increased production of nitric oxide by neutrophils and monocytes from cirrhotic patients with ascites and hyperdynamic circulation
Autor: | Pier Francesco Mannaioni, Giorgio La Villa, Laura Mugnai, Emanuela Masini, Antonella Simoni, Giacomo Laffi, Giuseppe Barletta, Paolo Gentilini, Marco Foschi |
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Rok vydání: | 1995 |
Předmět: |
Adult
Blood Platelets Lipopolysaccharides Liver Cirrhosis Male medicine.medical_specialty Platelet Aggregation Arginine Neutrophils Guanosine Monophosphate Guanosine Nitric Oxide Tritium Monocytes Nitric oxide Superoxide dismutase chemistry.chemical_compound Heart Rate Internal medicine Citrulline Humans Medicine Platelet Enzyme Inhibitors Aged Hepatology biology business.industry Superoxide Ascites Stroke Volume Middle Aged Endocrinology chemistry Hyperdynamic circulation biology.protein Female Nitric Oxide Synthase business Platelet Aggregation Inhibitors |
Zdroj: | Hepatology. 22:1666-1673 |
ISSN: | 1527-3350 0270-9139 |
DOI: | 10.1002/hep.1840220609 |
Popis: | 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) |
Databáze: | OpenAIRE |
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