Effect of etomidate on endothelium-dependent relaxation induced by acetylcholine in rat aorta.
The goals of this in vitro study were to investigate effects of etomidate on endothelium-dependent relaxation induced by acetylcholine in rat aorta, and to elucidate the associated cellular mechanism. In endothelium-intact rings precontracted with phenylephrine 10(-6) M, dose-response curves for acetylcholine (10(-9) to 10(-5) M) and calcium ionophore (10(-9) to 10(-6) M) were generated in the presence and absence of etomidate (5 x10(-6) 10(-5) M). In endothelium-intact or -denuded rings precontracted with phenylephrine 10(-6) M, sodium nitroprusside (10(-9) to 10(-6) M) dose-response curves were generated in the presence and absence of etomidate (10(-5)M). Etomidate (5 x10(-6), 10(-5)M) produced a significant rightward shift in the dose-response curves induced by acetylcholine (receptor-mediated endothelium-dependent agonist) and calcium ionophore A23187 (non receptor-mediated endothelium-dependent agonist). Etomidate (10(-5)M) had no effect on sodium nitroprusside (endothelium-independent nitric oxide donor)-induced vasorelaxant response in both endothelium-intact and -denuded rings. These results indicate that etomidate at clinically relevant concentrations attenuates endothelium-dependent relaxation induced by acetylcholine by an acting at a site distal to the endothelial muscarinic receptor, but proximal to guanylate cyclase activation of vascular smooth muscle in rat aorta.
Sohn
J-T
JT
Department of Anesthesiology and Pain Medicine, College of Medicine, Gyeongsang Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.
Kim
H J
HJ
Cho
H C
HC
Shin
I W
IW
Lee
H K
HK
Chung
Y K
YK
D000109:Acetylcholine / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005045:Etomidate / Q000494:pharmacology*; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D007476:Ionophores; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D000001:Calcimycin; D000109:Acetylcholine; D005045:Etomidate