Effects of reduced glutathione on contractile and diastolic functions of thoracic aorta of rats with obstructive jaundice

Abstract

Objective To evaluate the effects of reduced glutathione (GSH) on contractile and diastolic functions of the thoracic aorta of rats with obstructive jaundice.Methods Twenty-four adult male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 4 groups (n =6 each) using a random number table:sham operation group (group S),GSH group,bile duct ligation group (group BDL),and GSH + bile duct ligation group (group GSH + BDL).In GSH and GSH + BDL groups,GSH 300 mg/kg was infused via stomach everyday for 7 consecutive days,while the equal volume of normal saline was given in the other two groups.The common bile duct was ligated in the animals on 1 d after the end of intragastric administration in GSH and GSH + BDL groups.In GSH and GSH + BDL groups,after the model was established,GSH 300 mg/kg was infused via stomach everyday for 7 consecutive days,while the equal volume of normal saline was given in the other two groups.On 7th day after the model was extablished,blood samples were collected for determination of the levels of serum total bilirubin (TB),alanine aminotransferase (ALT) and aspartate aminotransferase (AST),tumor necrosis factor-alpha (TNF-α),interleukin-lβ (IL-1β) and 3-nitrotyrosine (3-NT),malondialdehyde (MDA),nitric oxide (NO) and GSH.The thoracic aortic rings were obtained and perfused with different concentrations of norepinephrine (NE),acetylcholine (Ach) and sodium nitroprusside (SNP).The maximum contraction and dilatation of aortic rings were recorded and the percentage was calculated.Some thoracic aortic rings were obtained again and perfused with different concentrations of NE after removal of the endothelium or after being perfused with L-NAME (nitricoxide synthase inhibitor).The maximum contraction of aortic rings was recorded and the percentage was calculated.Results Compared with group S,the serum levels of TB,ALT,AST,TNF-α,IL-1β,MDA,3-NT,NO and GSH were significantly increased in group BDL,and the serum levels of TB,ALT,AST,MDA,GSH and NO were increased in group BDL + GSH,the percentage of the maximum contraction amplitude of aortic rings in response to NE was decreased,and the percentage of the maximum dilatation amplitude of aortic rings in response to Ach and SNP were decreased in groups BDL and BDL + GSH,and no significant changes were found in the parameters mentioned above in group GSH.Compared with group BDL,the serum levels of TB,ALT,AST,TNF-α,IL-1β,MDA,3-NT and NO were significantly decreased,the level of GSH was increased,the percentage of the maximum contraction amplitude of aortic rings in response to NE was increased,the percentage of the maximum dilatation amplitude of aortic rings in response to Ach was increased,and no significant change was found in the percentage of the maximum dilatation amplitude of aortic rings in response to SNP in group BDL + GSH.Compared with the aortic rings from which the endothelium was removed or which were perfused with L-NAME in group BDL,no significant change was found in the percentage of the maximum contraction amplitude of aortic rings after removal of the endothelium or after being perfused with L-NAME in response to NE in group BDL + GSH.Conclusion GSH can improve the contractile and diastolic functions of thoracic aorta of rats with obstructive jaundice and this effect depends on the vascular endothelium. Key words: Jaundice, obstructive ; Glutathione ; Aorta, thoracic