Effects of adenosine receptor antagonists on amitriptyline-induced vasodilation in rat isolated aorta

Abstract

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 EC₈₀ of noradrenalin (NA) (the concentration of noradrenalin that produces 80% of maximal contractile response) as 10⁻⁵M, the IC₅₀ value of amitriptyline was measured in rat isolated aorta (the drug concentration causing a half- maximal inhibition of contractile responses to NA); IC₅₀ of amitriptyline was then compared in the presence of the DPCPX (a selective adenosine A₁ 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 × 10⁻⁵M (IC₅₀). While DPCPX increased amitriptyline-induced inhibition on contractile response to NA dose dependently, CSC decreased the contractile response to NA only at 10⁻⁵M. DMSO did not change amitriptyline-induced IC₅₀. Conclusion. Adenosine A_2a receptor stimulation seems to be responsible partly for amitriptyline-induced vasodilation and hypotension since the adenosine A₁ antagonist, DPCPX, increased amitriptyline-induced vasodilation in rat isolated aorta.

Keywords :

• Adenosine antagonists
• Amitriptyline toxicity
• Vasodilation
• Rat isolated aorta