Etomidate attenuates phenylephrine-induced contraction in isolated rat aorta.
OBJECTIVE
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.


CONCLUSIONS
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.
Shin
Il-Woo
IW
Department of Anesthesia and Pain Medicine, Gyeongsang National University, Hospital, 90 Chilam-dong, Jinju, Gyeongnam, 660-702, Republic of Korea.
Sohn
Ju-Tae
JT
Kim
Hee-Jin
HJ
Kim
Cheol
C
Lee
Heon-Keun
HK
Chang
Ki Churl
KC
Chung
Young-Kyun
YK
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005045:Etomidate / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D002121:Calcium Channel Blockers; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D012701:Serotonin; D011189:Potassium Chloride; D014700:Verapamil; D005045:Etomidate