Etomidate attenuates phenylephrine-induced contraction in isolated rat aorta

• Published in: Canadian journal of anesthesia 2005-11, Vol.52 (9), p.927-934
• Main Authors: Shin, Il-Woo, Sohn, Ju-Tae, Kim, Hee-Jin, Kim, Cheol, Lee, Heon-Keun, Chang, Ki Churl, Chung, Young-Kyun
• Format: Article
• Language: English
• Subjects: Anesthetics, Intravenous - pharmacology; Animals; Aorta, Thoracic - drug effects; Calcium Channel Blockers - pharmacology; Etomidate - pharmacology; In Vitro Techniques; Male; Muscle Contraction - drug effects; Muscle, Smooth, Vascular - drug effects; Phenylephrine - antagonists & inhibitors; Phenylephrine - pharmacology; Potassium Chloride - antagonists & inhibitors; Potassium Chloride - pharmacology; Rats; Rats, Sprague-Dawley; Serotonin - pharmacology; Signal Transduction - drug effects; Vasoconstrictor Agents - antagonists & inhibitors; Vasoconstrictor Agents - pharmacology; Verapamil - pharmacology
• ISSN: 0832-610X
• DOI: 10.1007/BF03022053

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. 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). 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. 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.