Correlation of nitric oxide and atrial natriuretic peptide changes with altered cGMP homeostasis in liver cirrhosis.
BACKGROUND
Cyclic GMP (cGMP) concentration is increased in plasma of patients with liver cirrhosis. Three possible mechanisms may contribute: increased cGMP synthesis by soluble (activated by nitric oxide), or particulate (activated by atrial natriuretic peptide (ANP)) guanylate cyclase or increased release from cells.


OBJECTIVE
The aim of this work was to analyze the possible contributors to increased plasma cGMP and to assess whether changes in the parameters of the system vary with the degree of liver disease (Child Pugh score) or by the presence of ascites.


METHODS
We measured cGMP in plasma and lymphocytes, soluble guanylate cyclase activation by nitric oxide in lymphocytes, nitrates and nitrites and ANPs (activator of particulate guanylate cyclase) in plasma. We analyzed the correlation between changes in different parameters to discern which parameters contribute to increased plasma cGMP.


RESULTS
The plasma content of nitrates+nitrites, ANP and cGMP are increased. Activation of soluble guanylate cyclase by nitric oxide is increased in patients while basal cGMP in lymphocytes is decreased.


CONCLUSIONS
Both increased ANP and increased activation of soluble guanylate cyclase by nitric oxide contribute to increased plasma cGMP in patients. The concentrations of ANP and cGMP in plasma increase with the degree of disease and are higher in patients with ascites.
Servicio de Hepatología, Hospital Clínico Universitario, Departamento de Medicina, Universidad de Valencia, Valencia, Spain.
Carmina
C
Montoliu
Elena
E
Kosenko
Juan A
JA
Del Olmo
Miguel A
MA
Serra
José M
JM
Rodrigo
Vicente
V
Felipo
D000328:Adult; D000368:Aged; D001201:Ascites / Q000097:blood / Q000209:etiology / Q000473:pathology; D009320:Atrial Natriuretic Factor / Q000097:blood*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000097:blood*; D006162:Guanylate Cyclase / Q000096:biosynthesis; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000097:blood; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology
D009566:Nitrates; D009573:Nitrites; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D010396:Penicillamine; D006152:Cyclic GMP