七氟醚并不改变糖尿病大鼠主动脉中去甲肾上腺素引起的细胞内 Ca²(+)变化。

Sevoflurane does not alter norepinephrine-induced intracellular Ca²(+) changes in the diabetic rat aorta.

机构信息

Department of Anesthesiology, Japanese Red Cross Society Wakayama Medical Centre, Japan.

出版信息

Can J Anaesth. 2010 Dec;57(12):1095-101. doi: 10.1007/s12630-010-9387-0. Epub 2010 Sep 16.

DOI:10.1007/s12630-010-9387-0

PMID:20845014

Abstract

PURPOSE

The effect of volatile anesthetics on the mechanism(s) of vascular contraction in diabetes mellitus (DM) has not been fully understood. The current study was designed to determine the effects of sevoflurane on the norepinephrine (NE)-induced changes in contractile state and intracellular Ca²(+) concentrations (Ca²(+)) in the spontaneously developing type 2 DM rat.

METHODS

The effects of sevoflurane on NE (10⁻⁶M)-induced vasoconstriction and increase in Ca²(+) in the aortas from Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 DM model, and from age-matched control Long-Evans Tokushima Otsuka (LETO) rats were investigated using an isometric force transducer and fluorometer with fura-2 as an indicator of Ca²(+).

RESULTS

Norepinephrine-induced increases in tension and Ca²(+) in OLETF rats were 54.8%, 95% confidence interval (CI) 36.9-72.6% and 58.8%, 95% CI 51.5-66.1%, respectively, and in LETO rats they were 46.4%, 95% CI 39.0-53.7% and 53.8%, 95% CI 46.9-60.7%, respectively, when expressed as the percentage relative to that induced by KCl 30 mM. In LETO rats, sevoflurane at a concentration of 3.4% inhibited the vascular contraction (9.4%, 95% CI 6.3-12.6%; P < 0.001) and the increase in Ca²(+) (33.3%, 95% CI 27.4-39.2%; P = 0.002). In OLETF rats, however, sevoflurane failed to affect either the NE-induced contraction (43.6%, 95% CI 28.3-58.9%; P = 0.68) or the elevation in Ca²(+) (60.5%, 95% CI 56.3-64.8%; P = 0.93).

CONCLUSION

Sevoflurane at clinically relevant concentrations inhibited the NE-induced increase in Ca²(+) in the aortic smooth muscle from normal rats but not in that from type 2 DM rats. Thus, a Ca²(+)- signalling pathway resistant to sevoflurane appears to exist in the type 2 DM rat aorta.

摘要

目的

挥发性麻醉剂对糖尿病（DM）血管收缩机制的影响尚未完全阐明。本研究旨在确定七氟醚对自发性 2 型 DM 大鼠主动脉中去甲肾上腺素（NE）诱导的收缩状态和细胞内 Ca²⁺浓度（[Ca²⁺]i）变化的影响。

方法

使用等长力换能器和荧光计，以 fura-2 作为 [Ca²⁺]i 的指示剂，研究七氟醚对 Otsuka Long-Evans Tokushima Fatty（OLETF）大鼠，即 2 型 DM 模型，和年龄匹配的对照 Long-Evans Tokushima Otsuka（LETO）大鼠的 NE（10⁻⁶M）诱导的血管收缩和 [Ca²⁺]i 增加的影响。

结果

OLETF 大鼠 NE 诱导的张力和 [Ca²⁺]i 增加分别为 54.8%，95%置信区间（CI）36.9-72.6%和 58.8%，95%CI 51.5-66.1%，而 LETO 大鼠分别为 46.4%，95%CI 39.0-53.7%和 53.8%，95%CI 46.9-60.7%，以 KCl 30mM 诱导的百分比表示。在 LETO 大鼠中，浓度为 3.4%的七氟醚抑制血管收缩（9.4%，95%CI 6.3-12.6%；P < 0.001）和 [Ca²⁺]i 增加（33.3%，95%CI 27.4-39.2%；P = 0.002）。然而，在 OLETF 大鼠中，七氟醚未能影响 NE 诱导的收缩（43.6%，95%CI 28.3-58.9%；P = 0.68）或 [Ca²⁺]i 的升高（60.5%，95%CI 56.3-64.8%；P = 0.93）。