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雌激素调节自发性高血压大鼠的血管肾上腺素能反应性。

Oestrogen modulates vascular adrenergic reactivity of the spontaneously hypertensive rat.

作者信息

Brandin Lisa, Bergström Göran, Manhem Karin, Gustafsson Helena

机构信息

Clinical Experimental Research Laboratory, Heart and Lung Institute, Sahlgrenska University Hospital/Ostra, Sweden.

出版信息

J Hypertens. 2003 Sep;21(9):1695-702. doi: 10.1097/00004872-200309000-00019.

Abstract

BACKGROUND

Male spontaneously hypertensive rats (SHRs) show an increased vascular neurogenic response compared with normotensive Wistar-Kyoto (WKY) control rats.

OBJECTIVE

To study the vascular adrenergic response in hypertensive and normotensive female rats, with a focus on the influence of oestrogen.

METHODS

Female SHRs and WKY rats were allocated randomly to a control group or to groups to undergo ovariectomy or ovariectomy combined with oestrogen supplementation (17beta-oestradiol 150 microg/kg per day) for either 1 day (group 1E2) or 10 days (group 10E2). Mean arterial pressure (MAP) was recorded and small mesenteric arteries were mounted in a Multi Myograph 610M. Vascular reactivities to transmural nerve stimulation (TNS), exogenous noradrenaline and acetylcholine were analysed.

RESULTS

MAP was significantly greater in SHRs than in WKY rats in all groups studied. Sensitivity to cumulative TNS (0.12-32 Hz) did not differ between vessels from control SHRs and WKY rats, expressed as the frequency giving 50% of maximal neurogenic response (Ef(50): 4.1 +/- 1.1 and 4.0 +/- 1.6 Hz, respectively). However, there was a greater reactivity to TNS in ovariectomized SHRs than in ovariectomized WKY rats (Ef(50) 1.8 +/- 0.7 and 6.8 +/- 2.2 Hz, respectively; P < 0.05). Oestradiol treatment significantly decreased the sensitivity to TNS in ovariectomized SHRs (P < 0.05), and after 10 days the frequency-response curves were almost identical (Ef(50) 6.3 +/- 1.9 Hz for group 10E2 SHRs and 5.6 +/- 0.8 Hz for group 10E2 WKY rats). The increased adrenergic reactivity in ovariectomized SHRs was inhibited by prazosin, an alpha(1)-adrenergic antagonist, and could not be explained by differences in endothelial function or sensitivity to applied noradrenaline.

CONCLUSION

Increased adrenergic reactivity is not present in small arteries from female SHRs. The findings of this study suggest that oestrogen acts on prejunctional mechanisms, reducing full expression of hypertension and peripheral vascular pathology.

摘要

背景

与血压正常的Wistar-Kyoto(WKY)对照大鼠相比,雄性自发性高血压大鼠(SHR)的血管神经源性反应增强。

目的

研究高血压和血压正常的雌性大鼠的血管肾上腺素能反应,重点关注雌激素的影响。

方法

将雌性SHR和WKY大鼠随机分为对照组,或接受卵巢切除术组,或卵巢切除术联合雌激素补充组(17β-雌二醇150μg/kg/天),分别持续1天(1E2组)或10天(10E2组)。记录平均动脉压(MAP),并将小肠系膜动脉安装在多通道血管张力测定仪610M上。分析血管对跨壁神经刺激(TNS)、外源性去甲肾上腺素和乙酰胆碱的反应性。

结果

在所有研究组中,SHR的MAP均显著高于WKY大鼠。对照SHR和WKY大鼠血管对累积TNS(0.12 - 32Hz)的敏感性无差异,以产生最大神经源性反应50%的频率表示(Ef(50):分别为4.1±1.1Hz和4.0±1.6Hz)。然而,去卵巢SHR对TNS的反应性高于去卵巢WKY大鼠(Ef(50)分别为1.8±0.7Hz和6.8±2.2Hz;P<0.05)。雌二醇治疗显著降低了去卵巢SHR对TNS的敏感性(P<0.05),10天后频率-反应曲线几乎相同(10E2组SHR的Ef(50)为6.3±1.9Hz,10E2组WKY大鼠为5.6±0.8Hz)。去卵巢SHR中肾上腺素能反应性的增加被α(1) - 肾上腺素能拮抗剂哌唑嗪抑制,且不能用内皮功能或对应用去甲肾上腺素的敏感性差异来解释。

结论

雌性SHR的小动脉中不存在肾上腺素能反应性增加。本研究结果表明,雌激素作用于节前机制,减少高血压和外周血管病变的充分表达。

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