Effects of dexmedetomidine on porcine pulmonary artery vascular smooth muscle

The 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.

Endothelium-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.

Dex 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.

Dex-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.