title: Adenosine-mediated cardiovascular toxicity in amitriptyline-poisoned rats.
abstract: We investigated the contribution of endogenous adenosine to amitriptyline-induced cardiovascular toxicity in rats. A control group of rats was pretreated with intraperitoneal (i.p.) 5% dextrose and received intravenous 0.94 mg/kg/min of amitriptyline for 60 minutes. The second and third groups of rats pretreated with i.p. 10 mg/kg of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor, and i.p. 1 mg/kg of S-(4-nitrobenzyl)-6-thioinosine (NBTI), a facilitated adenosine transport inhibitor, received 5% dextrose and amitriptyline infusion, respectively. Outcome parameters were mean arterial pressure (MAP), heart rate (HR), QT and QRS durations, and plasma adenosine concentrations. Plasma adenosine concentrations were increased in all groups. In the control group, amitriptyline decreased MAP and HR and prolonged QT and QRS durations after 10 minutes of infusion. In EHNA/NBTI-pretreated rats, amitriptyline prolonged QRS duration at 10 and 20 minutes. In EHNA/NBTI pretreated rats, amitriptyline-induced MAP, HR reductions, and QRS prolongations were more significant than that of dextrose-infusion-induced changes. Our results indicate that amitriptyline augmented the cardiovascular effects of endogen adenosine by increasing plasma levels of adenosine in rats.
authors.affiliation: Department of Pharmacology, Dokuz Eylul University School of Medicine, Izmir, Turkey. sule.kalkan@deu.edu.tr
authors.forename: Sule
authors.initials: S
authors.lastname: Kalkan
authors.forename: Nil
authors.initials: N
authors.lastname: Hocaoglu
authors.forename: Kubilay
authors.initials: K
authors.lastname: Oransay
authors.forename: Mujgan
authors.initials: M
authors.lastname: Buyukdeligoz
authors.forename: Yesim
authors.initials: Y
authors.lastname: Tuncok
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000097:blood / Q000378:metabolism*; D000639:Amitriptyline / Q000506:poisoning*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000506:poisoning*; D062186:Arterial Pressure / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D013868:Thioinosine; C010192:9-(2-hydroxy-3-nonyl)adenine; C001789:4-nitrobenzylthioinosine; D005947:Glucose; D000225:Adenine; D000241:Adenosine