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雌激素替代疗法通过外周动脉β肾上腺素能受体介导的血管舒张来减轻应激引起的升压反应。

Estrogen replacement attenuates stress-induced pressor responses through vasorelaxation via β-adrenoceptors in peripheral arteries of ovariectomized rats.

机构信息

Department of Environmental Health, Faculty of Life Science and Human Technology, Nara Women's University , Nara , Japan.

出版信息

Am J Physiol Heart Circ Physiol. 2018 Feb 1;314(2):H213-H223. doi: 10.1152/ajpheart.00148.2017. Epub 2017 Oct 13.

Abstract

We examined whether chronic estrogen replacement has an inhibitory effect on stress-induced pressor responses via activation of β-adrenoceptor (AR) in peripheral arteries of ovariectomized rats. Female Wistar rats aged 9 wk were ovariectomized. After 4 wk, pellets containing either 17β-estradiol (E) or placebo (Pla) were subcutaneously implanted into the rats. After 4 wk of treatment, rats underwent cage-switch stress, and, in a separate experiment, a subset received an infusion of isoproterenol (ISO) with or without pretreatment with the β-AR blocker atenolol or the β-AR blocker butoxamine. In addition, the isolated mesenteric artery was used to assess the concentration-related relaxing responses to ISO and the β- or β-AR mRNA level. The cage-switch stress-induced pressor response was significantly attenuated in the E-treated group compared with the Pla-treated group. Pretreatment with atenolol reduced blood pressure responses in both groups. However, butoxamine enhanced the pressor response only in the E-treated group, resulting in no difference between the two groups. In addition, the intravenous ISO-induced depressor response was significantly enhanced in the E-treated group compared with the Pla-treated group. Furthermore, the difference in the depressor response was abolished by pretreatment with butoxamine but not by atenolol. In the isolated mesenteric artery, butoxamine caused a rightward shift in ISO-induced concentration-related relaxation in the E-treated group. The β-AR mRNA level in the mesenteric artery was higher in the E-treated group than in the Pla-treated group. These results suggest that estrogen replacement attenuated the stress-induced pressor response probably by suppressing vasoconstriction via activation of β-ARs in peripheral arteries of ovariectomized rats. NEW & NOTEWORTHY In this study, we show, for the first time, that estrogen replacement has an inhibitory effect on the psychological stress-induced pressor response through vasorelaxation via β-adrenoceptors, probably due to overexpression of β-adrenoceptor mRNA, in peripheral arteries of ovariectomized rats.

摘要

我们研究了慢性雌激素替代疗法是否通过激活去卵巢大鼠外周动脉中的β-肾上腺素能受体(AR)对应激引起的升压反应产生抑制作用。将 9 周龄的雌性 Wistar 大鼠去卵巢。4 周后,将含有 17β-雌二醇(E)或安慰剂(Pla)的丸剂皮下植入大鼠体内。治疗 4 周后,大鼠进行笼切换应激,在另一个实验中,一部分大鼠接受异丙肾上腺素(ISO)输注,或在预先给予β-AR 阻滞剂阿替洛尔或β-AR 阻滞剂丁氧胺后给予 ISO 输注。此外,还使用分离的肠系膜动脉来评估 ISO 和β-或β-AR mRNA 水平的浓度相关舒张反应。与 Pla 处理组相比,E 处理组的笼切换应激引起的升压反应明显减弱。阿替洛尔预处理降低了两组的血压反应。然而,丁氧胺仅增强了 E 处理组的升压反应,导致两组之间无差异。此外,与 Pla 处理组相比,E 处理组静脉内 ISO 引起的降压反应明显增强。此外,丁氧胺预处理消除了差异,但阿替洛尔预处理没有消除差异。在分离的肠系膜动脉中,丁氧胺引起 E 处理组 ISO 诱导的浓度相关松弛向右移位。E 处理组肠系膜动脉中的β-AR mRNA 水平高于 Pla 处理组。这些结果表明,雌激素替代可能通过激活去卵巢大鼠外周动脉中的β-AR 来抑制血管收缩,从而减轻心理应激引起的升压反应。本研究首次表明,雌激素替代通过β-肾上腺素能受体介导的血管舒张对去卵巢大鼠外周动脉中的心理应激引起的升压反应产生抑制作用,这可能是由于β-肾上腺素能受体 mRNA 的过度表达。

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