Hepatic and extra-hepatic stimulation of glutathione release into plasma by norepinephrine in vivo

Studies were conducted to determine the effect of norepinephrine (NE) on re duced glutathione (GSH) and oxidized glutathione (GSSG) export from hepatic and extra-hepatic tissues in vivo. Anesthetized Single Comb White Leghorn (SCWL) males were implanted with cannulae in the carotid artery, hepatic ve in (HV) and hepatic portal veins (PV), and the left bile duct. In Experimen t 1, GSH and GSSG in hepatic and portal venous plasma and bile were determi ned prior to, during, and following two 20-min infusions of NE (2 and 10 mu g/ min per kg BW) into the hepatic PV. The lower NE infusion rate increased hepatic venous GSH (indicative of increased GSH export into liver sinusoid s) without affecting systemic or hepatic vascular pressures; however, it ha d no affect on portal venous GSH. The higher NE infusion rate increased GSH in the HV and hepatic PV (indicative of extra hepatic export of glutathion e) as well as systemic pressure, hepatic and portal venous pressures, and t he transhepatic pressure gradient. Biliary secretion of GSH and GSSG was un affected by either rate of NE infusion in Experiment 1. In Experiment 2, pr etreatment of birds with phentolamine, an alpha -adrenergic receptor blocke r (alpha -block), abolished sinusoidal export GSH as well as the ability of NE to stimulate GSH release from hepatic and extra-hepatic tissue. Althoug h HV and PV pressures were lower in alpha -block birds compared with contro ls, there were no differences in the transhepatic pressure gradient between groups. Plasma GSSG was below the limits of detection in Experiments 1 and 2. The combined results of Experiments 1 and 2 indicate that hepatic expor t of GSH was independent of changes in systemic or hepatic vascular pressur es or changes in the transhepatic pressure gradient. The results of these s tudies are the first to demonstrate that export of GSH into plasma in vivo is mediated by an alpha -receptor-mediated mechanism in hepatic and extra-h epatic tissues. The findings may be particularly important with regard to a ntioxidant homeostasis of animals during periods of stress.