Akademik Veri Yönetim Sistemi
2005 North American Congress of Clinical Toxicology Annual Meeting, Florida, Amerika Birleşik Devletleri, 9 - 14 Eylül 2005, cilt.43, sa.6, ss.730-731
Background: Previously, we demonstrated that adenosine receptor antagonists prevented hypotension in an invivo rat model of
amitriptyline toxicity. Activation of A1 receptor produces negative chronotropic and inotropic actions, whereas activation of A2a
receptor causes peripheral vasodilation. It is not clear that whether adenosine receptors in heart or in vasculature are dominant
for amitriptyline toxicity. In this study, we investigated the role of A2a receptors on vasodilation induced by
amitriptyline. Methods: Thoracic aortic rings obtained from rats were suspended in an isolated organ bath. EC80 values of
noradrenalin (NA) was obtained (109
–105 M, cumulatively). Tissues were first contracted with reference concentration of
NA (105 M). After the contractile response had been reached plateau, rings were washed and incubated with different
concentrations of amitriptyline and NA was administered again. IC50 values of amitriptyline was calculated as the drug
concentration causing a half-maximal inhibition of contractile responses to NA. In experimental groups, tissues were contracted with NA. Following the washout period, different doses of the DPCPX (a selective A1 antagonist, 109
–105 M) or CSC (a
selective A2a antagonist, 109
–105 M) or DMSO (solvent) were incubated before the amitriptyline incubation. NA was
administered following incubation period. Amitriptyline-induced half maximal inhibition of contractile response to NA were
compared in the presence of the DPCPX, CSC or DMSO. Student’s t test was used for statistical analysis. Result: Amitriptyyline (IC50 value: 1.8105 M) inhibited contractile response of NA by 49.9±3.7%. DPCPX increased amitriptyline-induced
inhibition on contractile response of NA in a concentration-dependent manner (53.7±2.4% p>0.05; 59.7±3.3% p>0.05;
70.6±4.6% p<0.01; 70.5±2.7% p<0.001; 71.9±3.7% p<0.001 respectively 109
–105 M). CSC decreased amitriptylineinduced inhibition on contractile response of NA at only a high concentration (105 M, 39.2±1.7%, p<0.05). Conclusion: Adenosine A2a receptor stimulation seems to be partly responsible for amitriptyline-induced vasodilation
and hypotension.