EFFECTS OF GENERAL ANESTHETICS ON INTRACELLULAR CALCIUM CONCENTRATION AND NITRIC OXIDE PRODUCTION OF VASCULAR ENDOTHELIUM

血管内皮细胞内Ca^2+浓度（[Ca^2+] i）的升高对血管内皮细胞产生一氧化氮（NO）是必不可少的。本研究的第一个目的是阐明受体依赖性和非依赖性内皮激活剂对内皮细胞[Ca^<2+>]_i和NO产生的影响。第二个目的是研究麻醉剂对牛主动脉内皮细胞[Ca^<2 +>] i与NO生成的关系。在340和380 nm的激发波长和510 nm的发射波长下进行荧光测量。用340/380荧光比值（R340/380）作为[Ca^2+]_i的指标，缓激肽（10 nM）引起内皮细胞[Ca^2+]_i迅速升高，随后逐渐下降至高于静息水平的持续平台。初始相可能是由细胞内Ca^<2+>释放引起的，持续相可能是由Ca^<2+>内流引起的。与受体非依赖性激动剂缓激肽相反，A23187（100 nM）诱导内皮细胞[Ca^2+]_i的双相增加。静脉麻醉药氯胺酮（100μM）和依托咪酯（100μM）可减弱缓激肽引起的[Ca^<2+>]_i峰值和持续相的升高。氯胺酮和依托咪酯均不改变A23187诱导的[Ca^2+] i瞬变，氯胺酮和依托咪酯通过抑制受体激活引起的内皮细胞[Ca^2+] i瞬变，选择性地减弱受体介导的内皮依赖性血管舒张反应。

An elevation of intracellular Ca^<2+> concentration ([Ca^<2+>]_i) is essential for nitric oxide (NO) production in vascular endothelium. The first goal of this study to elucidate the change in endothelial [Ca^<2+>]_i and NO production induced by receptor-dependent and -independent endothelial activators. The second goal was to investigate the effects of anesthetics on the relationship between [Ca^<2+>]_i and NO production.Bovine aortic endothelial cells were loaded with fluorescence Ca^<2+> indicator, fura-2/AM (5μM). Fluorescence measurements were performed at excitation wavelength of 340 and 380 nm and an emission wavelength of 510nm. The 340/380 fluorescence ratio (R340/380) was used as an indicator of [Ca^<2+>]_i.Bradykinin (10nM) elicited a rapid increase in endothelial [Ca^<2+>]_i followed by a gradual decline to a sustained plateau above the resting level. The initial phase was likely caused by intracellular Ca^<2+> release, and the sustained phase was caused by Ca^<2+> influx. In contrast to bradykinin, receptor-independent agonist, A23187 (100nM) induced a monophasic increase in endothelial [Ca^<2+>]_i. Intravenous anesthetics, ketamine (100μM) and etomidate(100μM) attenuated increases in [Ca^<2+>]_i at the peak and sustained phases in response to bradykinin. Neither ketamine nor etomidate altered A23187-induced [Ca^<2+>]_i transient.Ketamine and etomidate selectively attenuated receptor-mediated endothelium-dependent vasorelaxation by inhibiting of the endothelial [Ca^<2+>]_i transient in response to receptor activation.