쥐의 대동맥에서 acetylcholine에 의하여 유도된 내피세포 의존성 혈관이완에 대한 etomidate의 억제효과
Inhibitory Effects of Etomidate on Endothelium-Dependent Vasorelaxation Induced by Acetylcholine in Rat Aorta
대동맥 혈관내피세포 Acetylcholine 혈관이완 Etomidate;
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BACKGROUND: The previous study reported that etomidate attenuated vasorelaxant responses to acetylcholine and bradykinin by inhibiting both nitric oxide- and endothelium-derived hyperpolarizing factor-mediated components in canine pulmonary artery. The goals of this in vitro study were to investigate effects of etomidate on endothelium-dependent relaxation induced by acetylcholine, and to elucidate the associated cellular mechanism in rat aorta. METHODS: Isolated aortic rings with or without endothelium were suspended for isometric tension recording. In endothelium-intact rings precontracted with phenylephrine 10^(-6) M, dose-response curves for acetylcholine (10^(-9) to 10^(-5) M) and calcium ionophore A23187 (10^(-9) to 10%^(-6) M) were generated in the absence and presence of etomidate (5 × 10^(-6), 10^(-5) M). In endothelium-intact or denuded rings precontracted with phenylephrine 10^(-6) M, sodium nitroprusside (SNP, 10^(-9) to 10^(-6) M) dose-response curves were generated in the absence and presence of etomidate (10^(-5) M). Statistical analysis was performed using ANOVA or Student's t-test. Values are expressed as mean ± SD. RESULTS: Etomidate (5×10^(-6), 10^(-5) M) produced a significant rightward shift in dose-response curves (acetylcholine Log ED_(50) control: -7.32 ± 0.11, etomidate 5×10^(-6) M: -7.13 ± 0.12, etomidate 10^(-5) M: -6.98 ± 0.17, calcium ionophore A23187 Log ED_(50) control: -7.25 ± 0.28, etomidate 5×10^(-6) M: -6.72 ± 0.17, etomidate 10^(-5) M: -6.59 ± 0.17) induced by acetylcholine (receptor-mediated endothelium-dependent vasodilator) and calcium ionophore A23187 (non-receptor-mediated endothelium-dependent vasodilator). Etomidate (10^(-5) M) had no effect on SNP (nitric oxide donor)-induced vasorelaxant response in the aortic rings with endothelium or without endothelium. CONCLUSION: These results indicate that clinically relevant concentration (5×10^(-6)M) of etomidate attenuates endothelium-dependent relaxation induced by acetylcholine by an acting at site distal to endothelial muscarinic receptor-mediated response but proximal to guanylate cyclase activation of vascular smooth muscle in rat aorta.