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* From the Departments of Anesthesia and Pain Medicine, and
Pharmacology, and the Institute of Health Sciences,
Gyeongsang National University College of Medicine, Gyeongnam, Korea.
Address correspondence to: Dr. Ju-Tae Sohn, Department of Anesthesia and Pain Medicine, Gyeongsang National University, Hospital, 90 Chilam-dong, Jinju, Gyeongnam, 660-702, Republic of Korea. Phone: +82-55-750-8586; Fax: + 82-55-750-8142; E-mail: jtsohn{at}nongae.gsnu.ac.kr
Purpose: A previous study has shown that etomidate inhibits the angiotensin II-induced calcium influx in rat aortic smooth muscle cells. The goals of our current in vitro study were to investigate the effect of etomidate on phenylephrine-induced contraction in rat aorta, and to elucidate the associated signalling pathway.
Methods: Endothelium-denuded aortic rings were suspended for isometric tension recording. Concentration-response curves for phenylephrine (109 to 106 M), 5-hydroxytryptamine (107 to 104 M) and potassium chloride (10 to 60 mM) were generated in the presence and absence of etomidate (5 x 106, 3 x 105, 5 x 105 M). For the rings pretreated with verapamil (105 M), the phenylephrine concentration-response curves were generated in the presence and absence of etomidate (5 x 105 M). In the rings exposed to calcium-free isotonic depolarizing solution, the contractile response induced by the addition of calcium was assessed in the presence and absence of etomidate (5 x 105 M).
Results: Etomidate (5 x 105 M) produced a significant rightward shift in the concentration-response curves for phenylephrine, 5-hydroxytryptamine and potassium chloride. Etomidate (5 x 105 M) did not alter phenylephrine-induced contraction in the rings pretreated with verapamil. Etomidate (5 x 105 M) significantly attenuated the contractile response induced by the addition of calcium in the calcium-free isotonic depolarizing solution.
Conclusion: The results suggest that etomidate, which exceeds the clinically relevant concentration, attenuates the phenylephrine-induced contraction by having an inhibitory effect on the calcium influx by blocking the L-type calcium channels in the rat aortic vascular smooth muscle.
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