This study was designed to clarify the contribution of endogenous adenosine in the amitriptyline-induced cardiovascular toxicity mechanisms. Rats (n =24) were randomized into three groups. Control group received 5% dextrose i.p 1 hour ago before the amitriptyline infusion (0.94 mg/kg/min/60 minutes). Other rats pretreated 1 hour prior to experimental protocol with EHNA (inhibitor of adenosine deaminase, 10 mg/kg i.p) and NBTI (inhibitor offacilitated adenosine transport, 1mg/kg i.p). After EHNA/NBTI administrations, Group 2 received 5% dextrose, while Group 3 received amitriptylineinfusion. Mean arterial pressure (MAP), heart rate (HR), QT and QRS durations were recorded. Plasma adenosine concentrations were measured(HPLC). In the control group, plasma adenosine concentrations significantly increased after amitriptyline infusion (p < 0.05). In EHNA/NBTI administered groups, plasma adenosine concentrations significantly increased (P < 0.001). In the control group, amitriptyline infusion caused a significantdecrease in the MAP, HR and prolongation in QT and QRS durations after 10th min. (P < 0.001). In EHNA/NBTI administered group, a significantdecrease was found in the MAP (after 30th min.) and HR (after 40th min.) and prolongation in the QRS at 60th min.(p < 0.05). Amitriptyline infusionfollowing EHNA/NBTI administrations, caused a significant decrease in the MAP, HR and prolongation in the QT and QRS durations after 10th min. (P< 0.001). In EHNA/NBTI administered groups, amitriptyline-induced MAP (P < 0.01, after 20th min) and HR reductions (p < 0.05, after 40th min) andQRS prolongations (p < 0.05, after 10th min) were more significant than dextrose-induced reductions and prolongations. These results indicated thatamitriptyline enhanced plasma levels of adenosine and potantialized cardiovascular effects of endogenous adenosine.</p
