Nitric oxide and portal hypertension: a nitric oxide-releasing derivative of ursodeoxycholic acid that selectively releases nitric oxide in the liver.
Portal hypertension, a common consequence of chronic liver diseases, is directly responsible for most complications of cirrhosis. In liver microcirculation, nitric oxide is considered a major fine tuner of vascular tone by counterbalancing vasoconstrictors (sympathetic nervous activity, the renin-angiotensin system, and endothelin-1) in normal and cirrhotic livers. The deficiency of endothelial nitric oxide release is a key factor in the hemodynamic abnormalities associated with the dynamic component of portal hypertension. Conventional nitric oxide donors release nitric oxide into the blood stream, causing systemic hypotension and progression of vasodilatory syndrome in cirrhotic patients. NCX1000 is a nitric oxide-releasing derivative of ursodeoxycholic acid-derived compounds, being capable of selectively releasing nitric oxide into the liver circulation. Administration of NCX1000 to portal hypertensive rats decreases intrahepatic resistance providing a novel therapy for the treatment of portal hypertension.
Fiorucci
S
S
Gastrointestinal and Liver Unit, Department of Internal Medicine, University of Perugia, Perugia, Italy. fiorucci@unipg.it
Antonelli
E
E
Morelli
A
A
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*
C433771:2-methyl-3-(2-((4-nitrooxybutyloxy)carbonyl)vinyl)phenyl ursodeoxycholic acid ester; D009566:Nitrates; D009569:Nitric Oxide; D014580:Ursodeoxycholic Acid