The effect of 2-hydroxypropyl-β-cyclodextrin on amitriptyline-induced vasodilatation in isolated rat aorta

The aim of this study was to investigate the effects of 2-hydroxypropyl-β-cyclodextrin (2-HPBCD), which bound to amitriptyline with moderate-high affinity and 1: 1 selectivity, on amitriptyline induced vasodilatation. Nineteen male Wistar rats (345.1 ± 17.0 g) were used in the experiments. Thoracic aorta tissues from rats were suspended in rings in an in vitro organ bath system and vascular contraction responses of the tissues were recorded. At the beginning of the experiment, endothelial viability of the tissues were evaluated. Tissues with contraction response with potassium chloride (100 mM KCl, mean 1646.0±389.2 mg) followed by relaxation with acetylcholine (10-5 M ACh, 46.8±6.4%) were included in the study. In our study, firstly, it was evaluated whether high dose (1:20 molar ratio) 2-HPBCD alone had an effect on vascular contractile response (Group 1). Then, on the vascular contraction responses by adding amitriptyline (1.8x10-5 M) alone or amitriptyline 1:1, 1:4, 1:20 molar ratio together with amitriptyline in Group 2, Group 3 and Group 4 respectively. Contractile responses were obtained with norepinephrine (10-5 M NE) and then were compared each other. High dose alone (1:20 molar ratio) 2-HPBCD administration did not affect the contractile response (p>0.05). Amitriptyline alone (1.8x10-5 M) treated group showed a 45.3±5.6% reduction in contractile response. There was no statistically significant difference between the norepinephrine contractile responses obtained by 2-HPBCD incubation at 1:1 and 1:4 molar ratio with amitriptyline compared to the group treated with amitriptyline alone (p>0.05). Incubation of 2-HPBCD in a 1:20 molar ratio with amitriptyline was found to reduce the inhibition of amitriptyline-induced norepinephrine contractile response (p<0.05). In conclusion, high-dose 2-HPBCD was effective in preventing vasodilatation response with amitriptyline. Keywords: In vitro, amitriptyline, hypotension, vasodilatation, 2-hydroxypropyl-β-cyclodextrin