Haemodynamic effects of chronic tetramethylpyrazine administration on portal hypertensive rats.

Abstract

The purpose of this study was to investigate the therapeutic effects of tetramethylpyrazine, an alkaloid isolated from a Chinese herb Ligusticum wallichii Franch, on portal hypertensive rats. There were three groups of animals: partial portal vein ligated (PVL) rats, bile duct ligated (BDL) rats and sham-operated (Sham) rats. Each rat in every group was given only one of three treatment regimens: tetramethylpyrazine 30 or 50 mg/kg/12 h, or vehicle (0.2 N HCl, 0.7 ml/12 h). There were seven rats allocated to each regimen, with a total of 63 rats studied. Tetramethylpyrazine or vehicle was given via gastric gavage every 12 h for 8 days, starting just after PVL or 3 weeks after BDL, and haemodynamic parameters were measured thereafter. Both PVL and BDL rats exhibited portal hypertensive and hyperdynamic state as compared with Sham rats. Eight-day tetramethylpyrazine treatment induced dose-dependent reductions of portal venous pressure (PVP), mean arterial pressure (MAP), and total peripheral resistance (TPR) in both PVL and BDL rats. Tetramethylpyrazine at 30 and 50 mg/kg/12 h induced PVP reduction by 10.2 and 16.1% in PVL rats, and 10.5 and 14.8% in BDL rats, respectively, as compared with the vehicle group. There were no significant changes of cardiac index or heart rate (HR) after tetramethylpyrazine treatment in either PVL or BDL rats. In the Sham rats, tetramethylpyrazine did not significantly change PVP, MAP, HR or TPR, despite a tendency of reduction. Our results showed that 8-day treatment of tetramethylpyrazine induced reductions of both portal venous and systemic arterial pressure in portal hypertensive rats with and without cirrhosis. Overall, the therapeutic effects are neither outstandingly efficacious nor altogether beneficial.