Document Detail

Altered modulation of soluble guanylate cyclase by nitric oxide in patients with liver disease.
MedLine Citation:
PMID:  12602506     Owner:  NLM     Status:  MEDLINE    
The glutamate-nitric oxide-cGMP pathway is impaired in brain in vivo in animal models of chronic moderate hyperammonemia either with or without liver failure. The impairment occurs at the level of activation of soluble guanylate cyclase by nitric oxide (NO). It has been suggested that the impairment of this pathway may be responsible for some of the neurological alterations found in hyperammonemia and hepatic encephalopathy. Soluble guanylate cyclase is also present in lymphocytes. Activation of guanylate cyclase by NO is also altered in lymphocytes from hyperammonemic rats or from rats with portacaval anastomosis. We assessed whether soluble guanylate cyclase activation was also altered in human patients with liver disease. We studied activation of soluble guanylate cyclase in lymphocytes from 77 patients with liver disease and 17 controls. The basal content of cGMP in lymphocytes was decreased both in patients with liver cirrhosis and in patients with chronic hepatitis. In contrast, cGMP concentration was increased in plasma from patients with liver disease. Activation of guanylate cyclase by NO was also altered in liver disease and was higher in lymphocytes from patients with cirrhosis or hepatitis than that in lymphocytes from controls. Successful treatment with interferon of patients with hepatitis C reversed all the above alterations. Altered modulation of soluble guanylate cyclase by NO in liver disease may play a role in the neurological and hemodynamic alterations in these patients.
R Corbalán; C Montoliu; M D Miñana; J A Del Olmo; M A Serra; L Aparisi; J M Rodrigo; V Felipo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Metabolic brain disease     Volume:  17     ISSN:  0885-7490     ISO Abbreviation:  Metab Brain Dis     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2003-02-26     Completed Date:  2003-07-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8610370     Medline TA:  Metab Brain Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  295-301     Citation Subset:  IM    
Laboratory of Neurobiology, Instituto de Investigaciones Citológicas, FVIB, Valencia, Spain.
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MeSH Terms
Cyclic GMP / metabolism
Glutamic Acid / metabolism
Guanylate Cyclase / metabolism*
Hyperammonemia / enzymology
Liver Diseases / metabolism*
Nitric Oxide / metabolism*
Reg. No./Substance:
10102-43-9/Nitric Oxide; 56-86-0/Glutamic Acid; 7665-99-8/Cyclic GMP; EC Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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