Mechanism of acitretin-induced relaxations in isolated rat thoracic aorta preparations

Abstract

Acitretin is a member of vitamin A-derived retinoids, and its effect on vascular smooth muscle had not yet been studied. The aim of this study is to investigate the effect of acitretin, a retinoid, on vascular smooth muscle contractility. Thoracic aorta preparations obtained from 34 male Sprague–Dawley rats (355 ± 15 g) were studied in isolated organ baths containing Krebs–Henseleit solution. The relaxation responses were obtained with acitretin (10–12–10–4 M) in endothelium-preserved and endothelium-denuded aorta preparations precontracted with submaximal concentration of phenylephrine (10–6 M). The role of retinoic acid receptors (RARs), nitric oxide, adenylyl, and guanylyl cyclase enzymes, and potassium channels in these relaxation responses were investigated. Acitretin produced concentration-dependent relaxations, which were independent of its solvent dimethylsulfoxide (DMSO), in endothelium-denuded phenylephrine-precontracted thoracic aorta preparations. While incubation with the RAR antagonist (AGN193109, 10–5 M) had no effect on these relaxations; nitric oxide synthase inhibitor (L-NG-Nitro arginine methyl ester (L-NAME), 10–4 M), adenylyl cyclase inhibitor (SQ2253, 10–5 M), guanylyl cyclase inhibitor (oxadiazolo [4,3-a] quinoxalin-1-one (ODQ), 10–6 M), and potassium channel blocker (tetraethylammonium (TEA), 10–2 M) significantly eliminated the relaxation responses induced by acitretin. Acitretin induces relaxation in rat isolated thoracic aorta preparations without endothelium, which may be mediated by nitric oxide, cyclic adenosine monophosphate, and cyclic guanosine monophosphate-dependent kinases and potassium channels.