Effects of nitric oxide on leukotriene D4 decreased bile secretion in the perfused rat liver

Nitric oxide (NO) and leukotrienes are potent vasoactive agents that are involved in the control of portal blood flow. The present study investigated the role of leukotriene D4 and NO in a non-recirculating constant pressure rat liver perfusion model to analyse their interchanges on portal flow and bile secretion. The addition of leukotriene D4 (20 nM) to the perfusate for 5 minutes resulted in a decrease in portal blood flow (-55.3%), in bile flow (-24.4%) as well as bile acid release (-35.2%). In parallel, leukotriene D4 increased glucose output. The administration of a lower dose of leukotriene D4 (5 nM) reduced the respective parameters to a lesser degree, indicating dose-dependence. The addition of NO via the infusion of sodium nitroprusside (0.05 mM, 1 mM) reduced the effect of leukotriene D4 on portal flow, bile flow and bile acid secretion whereas the leukotriene D4 effects on hepatic glucose output remained unaffected. Correlation coefficient between decrease in portal flow and reduction of bile flow by infusing leukotriene D4 was R = 0.91, while in the presence of sodium nitroprusside R = 0.85. These results suggest that the leukotriene D4-induced cholestasis is dependent on portal flow. In contrast, hepatic vasoconstriction does not contribute to glycogenolysis stimulated by leukotriene D4 in the perfused liver.