Effects of adenosine receptor antagonists on amitriptyline-induced vasodilation in rat isolated aorta.
BACKGROUND
Although we have previously demonstrated the beneficial effects of adenosine receptor antagonists in preventing cardiovascular toxicity of amitriptyline in rats, it is not clear whether adenosine receptors in heart or in vasculature are dominant. The aim of the current study was to investigate the role of adenosine A(2a) receptors on amitriptyline-induced vasodilation in rat isolated aorta.


METHODS
After determining EC(80) of noradrenalin (NA) (the concentration of noradrenalin that produces 80% of maximal contractile response) as 10(-5)M, the IC(50) value of amitriptyline was measured in rat isolated aorta (the drug concentration causing a half- maximal inhibition of contractile responses to NA); IC(50) of amitriptyline was then compared in the presence of the DPCPX (a selective adenosine A(1) antagonist), CSC (a selective A(2a) antagonist) or DMSO (a solvent for adenosine antagonists). Statistical analysis was done using the Student t test.


RESULTS
Amitriptyline-inhibited 49.9 +/- 3.7 % contractile response to NA on aorta segments at 1.8 x 10(-5)M (IC(50)). While DPCPX increased amitriptyline-induced inhibition on contractile response to NA dose dependently, CSC decreased the contractile response to NA only at 10(-5)M. DMSO did not change amitriptyline-induced IC(50).


CONCLUSIONS
Adenosine A(2a) receptor stimulation seems to be responsible partly for amitriptyline-induced vasodilation and hypotension since the adenosine A(1) antagonist, DPCPX, increased amitriptyline-induced vasodilation in rat isolated aorta.
Kalkan
Sule
S
Dokuz Eylul University, School of Medicine, Department of Pharmacology, Izmir, Turkey. sule.kalkan@deu.edu.tr
Hocaoglu
Nil
N
Akgun
Aylin
A
Gidener
Sedef
S
Tuncok
Yesim
Y
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D018759:Adrenergic Uptake Inhibitors / Q000633:toxicity*; D000639:Amitriptyline / Q000633:toxicity*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000633:toxicity*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D018759:Adrenergic Uptake Inhibitors; D000929:Antidepressive Agents, Tricyclic; D014970:Xanthines; C081320:8-(3-chlorostyryl)caffeine; D000639:Amitriptyline; D002110:Caffeine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D004121:Dimethyl Sulfoxide