Altered modulation of soluble guanylate cyclase in lymphocytes from patients with liver disease.
Studies of animal models suggest that the activation of soluble guanylate cyclase by nitric oxide is altered in liver disease. We studied 77 patients with liver disease and 17 controls, to investigate whether the activation of soluble guanylate cyclase is altered in lymphocytes from patients with liver disease. The basal content of guanosine 3',5'-cyclic monophosphate (cGMP) in lymphocytes was decreased both in patients with liver cirrhosis (by 52%) and in patients with chronic hepatitis (by 62%). Activation of soluble guanylate cyclase by nitric oxide was higher in lymphocytes from patients with cirrhosis (3100+/-1000% of basal) or with hepatitis (5200+/-2500% of basal) than in lymphocytes from controls (1200+/-500% of basal). cGMP in plasma was increased in patients with liver disease. Successful (but not unsuccessful) treatment with interferon of patients with hepatitis due to virus C reversed all the above alterations. Altered modulation of soluble guanylate cyclase by nitric oxide in liver disease may play a role in the hemodynamic alterations found in these patients.
Corbalán
Regina
R
Laboratory of Neurobiology, Instituto de Investigaciones Citologicas, Fundación Valenciana de Investigaciones Biomedicas, Amadeo de Saboya, 4, 46010 Valencia, Spain.
Miñana
María-Dolores
MD
Del Olmo
Juan A
JA
Serra
Miguel A
MA
Rodrigo
José M
JM
Felipo
Vicente
V
D000328:Adult; D000368:Aged; D000242:Cyclic AMP / Q000097:blood; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000097:blood / Q000201:enzymology / Q000473:pathology; D006801:Humans; D022124:Hyperammonemia / Q000097:blood / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D008214:Lymphocytes / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D012995:Solubility
D009569:Nitric Oxide; D000242:Cyclic AMP; D006162:Guanylate Cyclase