Investigation of the mechanism of vascular relaxing effect of acitretin in isolated rat thoracic aorta preparations

Acitretin, a member of vitamin A-derived retinoids, provides proliferation and differentiation in epidermal cells. It also has immune-regulating, anti-inflammatory effects. Due to these effects, it can be used in the treatment of psoriasis. It shows its effects mainly via the nuclear localized retinoic acid receptor (RAR) and the retinoid X receptor (RXR). Based on the case reports of erection problems observed in acitretin users, relaxation was detected only in aorta preparations in a preliminary study which was conducted by us in order to investigate the possible effects of acitretin on smooth muscle (rat corpus cavernosum, thoracic aorta, stomach fundus, ileum preparations). In our thesis study, which was planned in the light of our preliminary study, we aimed to reveal the relaxing effect of acitretin on vascular smooth muscle tissue and the mechanism of this effect. The roles of alpha-1 adrenoceptors, RAR and RXR, nitric oxide (NO), adenylate / guanylate cyclase enzymes and potassium channels were investigated. In thoracic aorta ring preparations, isolated from male Sprague Dawley rats and suspended in organ baths containing Krebs Henseleit physiological solution; acitretin that was administered in increasing concentrations produced a relaxation response after phenylephrine pre-contraction. This effect was found to be independent of the solvent DMSO. Alpha-1 adrenoceptors and incubation with the RAR antagonist (AGN193109, 10-5 M, 2 hours) were found to have no effect on vascular smooth muscle relaxation responses obtained with acitretin. Incubation with the RXR antagonist (HX531, 10-5 M, 2 hours) increased the relaxant effect of acitretin in endothelium (-) preparations. Incubation with nitric oxide synthase inhibitor (L-NAME, 10-4 M, 30 minutes), adenylate cyclase inhibitor (SQ2253, 10-5 M, 30 minutes), guanylate cyclase inhibitor (ODQ, 10-6 M, 30 minutes) and non-specific K+ channel blocker (Tetraethylammonium - TEA, 10-2 M, 30 minutes) eliminated the relaxation responses obtained with acitretin. In the light of all these findings, It was concluded that nitric oxide, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)-dependent kinases and K+ channels may play a role in the relaxation responses of acitretin in endothelium (-) rat thoracic aorta preparations.