Effects of dexmedetomidine on porcine pulmonary artery vascular smooth muscle
Abstract Background Dexmedetomidine is added to local anesthetics to increase their potency and extend their duration of action, thus providing postoperative analgesia with a single administration. However, the effects and mechanism of action of dexmedetomidine on pulmonary arteries have not been determined. The aim of this study was to investigate the effect of dexmedetomidine on pulmonary artery vascular smooth muscle, evaluating changes in contraction tension. Methods Endothelium-denuded porcine pulmonary arteries were sliced into 2- to 3-mm rings. Changes in isometric contraction tension were measured with the addition of various substances at various concentrations, under different conditions of baseline stimulation (with KCl, Adrenaline, caffeine, or histamine) and different conditions of Ca2+ depletion with intracellular reservoirs or extracellular stores depleted. Results Dexmedetomidine increased the contraction tension induced by high-KCl depolarization in a concentration-dependent manner. Dexmedetomidine inhibited receptor-activated Ca2+ channels (RACCs) and phosphatidylinositol-1,4,5-triphosphate-induced Ca2+ release (IICR), but not Ca2+-induced Ca2+ release (CICR). Conclusions Dex increased the contraction tension resulting from depolarization stimulation by high KCl in a concentration-dependent manner in porcine pulmonary artery vascular smooth muscle. The enhancement of high KCl-induced contraction with Dex addition was mediated by α2 receptors. Dex suppressed increases in contraction tension induced by receptor stimulation with adrenaline, also in a concentration-dependent manner. Dex inhibited RACC and IICR, but not CICR. Elucidating the effects and mechanisms of action of Dex in the central arteries is likely to be useful as basic data for creating Dex-containing local anesthetics.