慢性间歇性低压缺氧降低自发性高血压大鼠下丘脑 N-甲基-d-天冬氨酸受体活性和交感神经外流

IF 1.6 4区 医学 Q4 BIOPHYSICS High altitude medicine & biology Pub Date : 2024-03-01 Epub Date: 2024-01-19 DOI:10.1089/ham.2023.0098
Xinqi Guo, Hongyu Ma, Ziye Cui, Qiyue Zhao, Ying Zhang, Lu Jia, Liping Zhang, Hui Guo, Xiangjian Zhang, Yi Zhang, Yue Guan, Huijie Ma
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引用次数: 0

摘要

郭欣琦、马宏宇、崔子晔、赵启悦、张颖、贾璐、张丽萍、郭慧、张湘健、张毅、关悦、马慧杰。慢性间歇性低压缺氧降低自发性高血压大鼠下丘脑N-甲基-d-天冬氨酸受体活性和交感神经外流00:000-000, 2024.目的:本研究旨在确定下丘脑肾素-血管紧张素系统(RAS)在慢性间歇性低压缺氧(CIHH)降压作用中的作用。研究方法Wistar-Kyoto(WKY)大鼠和自发性高血压大鼠(SHR)接受 35 天模拟海拔 4,000 米的低压缺氧,每天 5 小时。测定了各组大鼠的 RAS 水平、血压和下丘脑室旁核(PVN)交感神经前神经元的 N-甲基-d-天冬氨酸受体(NMDAR)活性。结果自 CIHH 治疗第三周起,SHR 的收缩压、舒张压和平均动脉血压(MAP)均显著下降。这种降压效果在停止 CIHH 治疗后可维持至少 2 周。CIHH 治疗还可减轻六甲氧氨嘧啶给药引起的 SHR 大鼠 MAP 和肾交感神经活性的降低,但对 WKY 大鼠没有影响。此外,CIHH 还逆转了 SHR 大鼠血清血管紧张素(Ang)II 浓度的升高、PVN 血管紧张素转换酶(ACE)和 AngII 1 型(AT1)受体的表达,以及血清 Ang1-7 浓度的降低和 PVN ACE2 和 Mas 受体的表达。此外,CIHH 还导致 SHR PVN 交感神经节前神经元的微型兴奋性突触后电流频率和 NMDAR 电流幅度降低,这说明 CIHH 降低了 SHR PVN 交感神经节前神经元突触前和突触后 NMDAR 的活性。然而,使用 A779(一种 Mas 受体阻断剂)或 AngII 预处理可减轻上述影响。同时,Ang1-7 预处理模拟了 CIHH 对 SHR 交感神经前元和突触后元 NMDAR 活性的影响。结论:我们的数据表明,CIHH 通过降低高血压患者下丘脑中 ACE/AngII/AT1 轴的活性和提高 ACE2/Ang1-7/Mas 轴的活性,降低了 PVN 交感神经前突触前后 NMDAR 的活性、交感神经外流和血压。
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Chronic Intermittent Hypobaric Hypoxia Reduces Hypothalamic N-Methyl-d-Aspartate Receptor Activity and Sympathetic Outflow in Spontaneously Hypertensive Rats.

Guo, Xinqi, Hongyu Ma, Ziye Cui, Qiyue Zhao, Ying Zhang, Lu Jia, Liping Zhang, Hui Guo, Xiangjian Zhang, Yi Zhang, Yue Guan, and Huijie Ma. Chronic intermittent hypobaric hypoxia reduces hypothalamic N-Methyl-d-Aspartate Receptor activity and sympathetic outflow in spontaneously hypertensive rats. High Alt Med Biol. 25:77-88, 2024. Objective: This study aims to determine the role of hypothalamic renin-angiotensin system (RAS) in the antihypertensive effect of chronic intermittent hypobaric hypoxia (CIHH). Methods: Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) received 35 days of hypobaric hypoxia simulating an altitude of 4,000 m, 5 h/day. The levels of RAS, blood pressure, and N-methyl-d-aspartate receptor (NMDAR) activities of hypothalamic paraventricular nucleus (PVN) presympathetic neurons from each group of rats were determined. Results: The systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure (MAP) of SHRs significantly decreased from the third week of CIHH treatment. This blood pressure reduction effect could be maintained for at least 2 weeks after stopping the CIHH treatment. CIHH treatment also attenuated the decrease in MAP and renal sympathetic nerve activity induced by hexamethonium administration in SHRs, but not in WKY rats. Furthermore, CIHH reversed the increase in serum angiotensin (Ang)II concentration and the expression of PVN angiotensin-converting enzyme (ACE) and AngII type 1 (AT1) receptors, as well as the decrease in serum Ang1-7 concentration and the expression of PVN ACE2 and Mas receptors in SHRs. In addition, the administration of CIHH resulted in a reduction in the frequency of miniature excitatory postsynaptic currents and amplitude of NMDAR current in PVN presympathetic neurons of SHRs, which means that CIHH decreased the pre- and postsynaptic NMDAR activity of PVN presympathetic neurons in SHRs. However, pretreatment with A779 (a Mas receptor blocker) or AngII abrogated the above effects. Meanwhile, Ang1-7 pretreatment mimicked the CIHH effect on pre- and postsynaptic NMDAR activity of presympathetic neurons in SHRs. Conclusions: Our data indicate that CIHH reduces pre- and postsynaptic NMDAR activity of PVN presympathetic neurons, sympathetic outflow, and blood pressure by decreasing the activity of the ACE/AngII/AT1 axis and increasing the activity of ACE2/Ang1-7/Mas axis in the hypothalamus in hypertension.

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来源期刊
High altitude medicine & biology
High altitude medicine & biology 医学-公共卫生、环境卫生与职业卫生
CiteScore
3.80
自引率
9.50%
发文量
44
审稿时长
>12 weeks
期刊介绍: High Altitude Medicine & Biology is the only peer-reviewed journal covering the medical and biological issues that impact human life at high altitudes. The Journal delivers critical findings on the impact of high altitude on lung and heart disease, appetite and weight loss, pulmonary and cerebral edema, hypertension, dehydration, infertility, and other diseases. It covers the full spectrum of high altitude life sciences from pathology to human and animal ecology.
期刊最新文献
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