• Mami Chikuda and Kenichi Sato.
• Division of Dental Anesthesiology, Department of Reconstructive Oral and Maxillofacial Surgery, School of Dentistry, Iwate Medical University, 1-3-27 Chuo-dori, Morioka, Iwate, 020-8505, Japan.
• BMC Anesthesiol. 2019 Sep 12; 19 (1): 176.

BackgroundThe α2-receptor agonist dexmedetomidine (Dex) has been shown to produce sedative and analgesic effects not only with systemic administration but also when administered in the extradural space and around peripheral nerves. The effects and mechanism of action of Dex on pulmonary arteries, however, have not been determined. This study therefore aimed to investigate the effect of Dex on pulmonary arterial vascular smooth muscle by evaluating changes in isometric contraction tension. We then attempted to determine the effects of Dex on depolarization stimulation and receptor stimulation.MethodsEndothelium-denuded porcine pulmonary arteries were sliced into 2- to 3-mm rings. We then exposed them to certain substances at various concentrations under different conditions of baseline stimulation (with KCl, adrenaline, caffeine, or histamine) and to α2-receptor stimulants or antagonists, or α1-receptor antagonists (imidazoline, yohimbine, rauwolscine, prazosin), and different conditions of Ca2+ depletion of the intracellular reservoir or extracellular stores. We measured the changes in isometric contraction tension with each addition or change in conditions.ResultsDex enhanced the contraction induced by high-concentration KCl stimulation. Dex-induced enhancement of contraction induced by high-concentration KCl was completely suppressed by yohimbine and rauwolscine, which are α2-receptor antagonists, but not by prazosin. Dex, imidazoline, yohimbine, and rauwolscine reduced the increases in contraction tension induced by the receptor stimulant adrenaline. Dex suppressed the adrenaline-induced increases in contraction tension after depletion of the Ca2+ reservoir. In the absence of extracellular Ca2+, Dex suppressed the adrenaline- and histamine-induced increases in contraction tension but did not affect caffeine-induced increases.ConclusionsDex-enhanced, high-concentration KCl-induced contraction was mediated by α2-receptors. Adrenaline-induced contraction was suppressed by the α2-receptor stimulant Dex and α2-receptor antagonists yohimbine and rauwolscine, suggesting that the effect of Dex on adrenaline-induced contraction is attributable to its α2-receptor-blocking action. Dex inhibited receptor-activated Ca2+ channels and phosphatidylinositol-1,4,5-triphosphate-induced Ca2+ release but not Ca2+-induced Ca2+ release.

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