Korean Journal of Anesthesiology

The Korean Society of Anesthesiologists (대한마취통증의학회)
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Dexmedetomidine-induced contraction of isolated rat aorta is dependent on extracellular calcium concentration

Ok, Seong-Ho;Bae, Sung-Il;Shim, Haeng-Seon;Sohn, Ju-Tae

  • Published : 20120900
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Abstract

Background: Dexmedetomidine is a highly selective ${\alpha}_{2}$-adrenoceptor agonist that is widely used for sedation and analgesia during the perioperative period. Intravenous administration of dexmedetomidine induces transient hypertension due to vasoconstriction via the activation of the ${\alpha}_{2}$-adrenoceptor on vascular smooth muscle. The goal of this in vitro study is to investigate the calcium-dependent mechanism underlying dexmedetomidine-induced contraction of isolated endothelium-denuded rat aorta. Methods: Isolated endothelium-denuded rat thoracic aortic rings were suspended for isometric tension recording. Cumulative dexmedetomidine concentration-response curves were generated in the presence or absence of the following inhibitors: ${\alpha}_{2}$-adrenoceptor inhibitor rauwolscine; voltage-operated calcium channel blocker verapamil (5 ${\times}$ $10^{-7}$, $10^{-6}$ and 5 ${\times}$ $10^{-5}$ M); purported inositol 1,4,5-trisphosphate receptor blocker 2-aminoethoxydiphenylborate (5 ${\times}$ $10^{-6}$, $10^{-5}$ and 5 ${\times}$ $10^{-5}$ M); phospholipase C inhibitor U-73122 ($10^{-6}$ and 3 ${\times}$ $10^{-6}$ M); and store-operated calcium channel inhibitor gadolinium chloride hexahydrate ($GD^{3+}$; 5 ${\times}$ $10^{-6}$ M). Dexmedetomidine concentration-response curves were also generated in low calcium concentrations (1 mM) and calcium-free Krebs solution. Results: Rauwolscine, verapamil, and 2-aminoethoxydiphenylborate attenuated dexmedetomidine-induced contraction in a concentration-dependent manner. Low calcium concentrations attenuated dexmedetomidine-induced contraction, and calcium-free Krebs solution nearly abolished dexmedetomidine-induced contraction. However, U-73122 and $GD^{3+}$ had no effect on dexmedetomidine-induced contraction. Conclusions: Taken together, these results suggest that dexmedetomidine-induced contraction is primarily dependent on extracellular calcium concentrations that contribute to calcium influx via voltage-operated calcium channels of isolated rat aortic smooth muscle. Dexmedetomidine-induced contraction is mediated by ${\alpha}_{2}$-adrenoceptor stimulation. Dexmedetomidine-induced contraction appears to be partially mediated by calcium release from the sarcoplasmic reticulum.

Keywords

References

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