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

• Published in: Clinical toxicology (Philadelphia, Pa.) Vol. 43; no. 6; pp. 730 - 731
• Main Authors: Kalkan, S, Hocaoglu, N, Akgun, A, Gidener, S, Tuncok, Y
• Format: Journal Article
• Language: English
• Published: 01.10.2005
• ISSN: 1556-3650

Previously, we demonstrated that adenosine receptor antagonists prevented hypotension in an invivo rat model of amitriptyline toxicity. Activation of A sub(1) receptor produces negative chronotropic and inotropic actions, whereas activation of A sub(2a) 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 A sub(2a) receptors on vasodilation induced by amitriptyline. Thoracic aortic rings obtained from rats were suspended in an isolated organ bath. EC sub(80) values of noradrenalin (NA) was obtained (10 super(-9)-10 super(-5) M, cumulatively). Tissues were first contracted with reference concentration of NA (10 super(-5) M). After the contractile response had been reached plateau, rings were washed and incubated with different concentrations of amitriptyline and NA was administered again. IC sub(50) 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 A sub(1) antagonist, 10 super(-9)-10 super(-5) M) or CSC (a selective A sub(2a) antagonist, 10 super(-9)-10 super(-5) 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. Amitriptyline (IC sub(50) value: 1.8 x 10 super(-5) M) inhibited contractile response of NA by 49.9 plus or minus 3.7%. DPCPX increased amitriptyline-induced inhibition on contractile response of NA in a concentration-dependent manner (53.7 plus or minus 2.4% p>0.05; 59.7 plus or minus 3.3% p>0.05; 70.6 plus or minus 4.6% p<0.01; 70.5 plus or minus 2.7% p<0.001; 71.9 plus or minus 3.7%, p<0.001 respectively 10 super(-9)-10 super(-5) M). CSC decreased amitriptyline-induced inhibition on contractile response of NA at only a high concentration (10 super(-5) M, 39.2 plus or minus 1.7%, p<0.05). Adenosine A sub(2a) receptor stimulation seems to be partly responsible for amitriptyline-induced vasodilation and hypotension.