Enhancement of endothelial nitric oxide production by chenodeoxycholic acids in patients with hepatobiliary diseases

The Purpose of this study was to clarify whether physiological concentratio ns of bile acids could affect endothelial nitric oxide production. We inves tigated the relationships between clinical concentrations of individual bil e acids observed in patients with hepatobiliary diseases and endothelial ni tric oxide production induced by each bile acid. Fifteen serum bile acids were measured using high-performance liquid chroma tography combined with enzymatic fluorometry in 8 patients with liver cirrh osis, obstructive jaundice, and 8 healthy subjects. The effects of individu al bile acids on nitric oxide production were examined in human umbilical e ndothelial cells by measuring the concentration of NO2- in the cultured med ium. NO release in the blood was also determined by measuring the NO2- / NO 3- concentration in these patients. In patients with hepatobiliary diseases, the plasma concentrations of cheno deoxycholic acid, ursodeoxycholic acid and cholic acid (free acid, taurine and glycine conjugates) were markedly elevated. Incubation of cells with ch enodeoxycholic acid and deoxycholic acid (free acid, taurine and,glycine co njugates) enhanced NO2- production in a concentration-dependent manner, whi le cholic acid free and its conjugates) did not. The effects of individual bile acids on nitric oxide production were additive. Patients with liver ci rrhosis and obstructive jaundice had higher plasma levels of NO2- / NO3- le vels than the control subjects. These results suggest that increased plasma concentrations of chenodeoxycho lic acid (free, taurine and glycine conjugates) in patients with hepatobili ary diseases may induce endothelial nitric oxide production. Thus, nitric o xide production induced by bile acids may be involved in the pathogenesis o f circulatory abnormalities in patients with liver diseases.