Does adenosine A(1) receptor stimulation causes QRS prolongation by blocking beta adrenergic receptors in amitriptyline poisoning?
OBJECTIVE
To investigate the role of beta receptor blockade via adenosine A(1) receptor stimulation on amitriptyline-induced QRS prolongation.


METHODS
Isolated rat hearts were randomized into three groups (n=8 for each group). After pretreatment with 5% dextrose (control) or DPCPX (8-cyclopentyl-1,3-dipropylxanthine), or propranolol + DPCPX, amitriptyline infusion was given to all groups. Intact beta adrenergic receptor response was verified with a bolus dose of isoproteranol (3 x 10(-5)M).


RESULTS
Amitriptyline (5.5 x 10(-5)M) infusion following pretreatment with 5% dextrose or 10(-4)M DPCPX prolonged QRS by 40-110% and 30-75%, respectively. After the beta receptor blockade with 10(-2)M propranolol bolus, amitriptyline infusion following pretreatment with DPCPX prolonged QRS by 40-130%. Amitriptyline infusion following pretreatment with DPCPX (10(-4)M) shortened the QRS at 40, 50 and 60 min significantly when compared to propranolol+DPCPX group (168.8+/-4.9%, p<0.05; 170.8+/-6.9%, p<0.01; 174.0+/-6.9%, p<0.01, respectively). Amitriptyline infusion following pretreatment with 5% dextrose prolonged QRS duration significantly at 50th minutes (209.5+/-6.1%, p<0.05) compared to DPCPX pretreatment group.


CONCLUSIONS
DPCPX pretreatment shortened amitriptyline-induced QRS prolongation. Beta adrenergic receptor blockade enhanced QRS prolongation shortened by DPCPX pretreatment. Adenosine A(1) receptor stimulation related to beta adrenergic receptor blockade may play a role in amitriptyline-induced QRS prolongation in isolated rat hearts.
Akgun Arici
M Aylin
MA
Dokuz Eylul University School of Medicine, Department of Pharmacology, Balcova, 35340 Izmir, Turkey. aylin.akgun@deu.edu.tr
Kalkan
Sule
S
Demir
Omer
O
Hocaoglu Aksay
Nil
N
Gidener
Sedef
S
Tuncok
Yesim
Y
D058907:Adenosine A1 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists; D000639:Amitriptyline / Q000506:poisoning*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000506:poisoning*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D058907:Adenosine A1 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000929:Antidepressive Agents, Tricyclic; D011943:Receptors, Adrenergic, beta; D014970:Xanthines; D000639:Amitriptyline; C051360:1,3-dipropyl-8-cyclopentylxanthine; D011433:Propranolol; D007545:Isoproterenol