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Canadian Journal of Anesthesia 52:927-934 (2005)
© Canadian Anesthesiologists' Society, 2005

General Anesthesia

Etomidate attenuates phenylephrine-induced contraction in isolated rat aorta

[L’étomidate atténue la contraction induite par la phényléphrine dans des aortes isolées de rats]

Il-Woo Shin, MD*, Ju-Tae Sohn, MD*,{ddagger}, Hee-Jin Kim, MD*, Cheol Kim, MD*, Heon-Keun Lee, MD*, Ki Churl Chang, PhD{dagger},{ddagger} and Young-Kyun Chung, MD*

* From the Departments of Anesthesia and Pain Medicine, and
{dagger} Pharmacology, and the Institute of Health Sciences,
{ddagger} 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 (10–9 to 10–6 M), 5-hydroxytryptamine (10–7 to 10–4 M) and potassium chloride (10 to 60 mM) were generated in the presence and absence of etomidate (5 x 10–6, 3 x 10–5, 5 x 10–5 M). For the rings pretreated with verapamil (10–5 M), the phenylephrine concentration-response curves were generated in the presence and absence of etomidate (5 x 10–5 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 10–5 M).

Results: Etomidate (5 x 10–5 M) produced a significant rightward shift in the concentration-response curves for phenylephrine, 5-hydroxytryptamine and potassium chloride. Etomidate (5 x 10–5 M) did not alter phenylephrine-induced contraction in the rings pretreated with verapamil. Etomidate (5 x 10–5 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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