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Chronic Intermittent Hypobaric Hypoxia Ameliorates Renal Vascular Hypertension Through Up-regulating NOS in Nucleus Tractus Solitarii

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Abstract

Chronic intermittent hypobaric hypoxia (CIHH) is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension (RVH). In this study, RVH was induced by the 2-kidney-1-clip method (2K1C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii (NTS) in anesthetized rats. Evoked excitatory postsynaptic currents (eEPSCs) and spontaneous EPSCs (sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHH-treated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and eNOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via up-regulating NOS expression in the NTS.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31071002, 31271223, 31671184, and 81800308), the National Basic Research Development Program of China (2012CB518200), and the Natural Science Foundation of Hebei Province (C2012206001), China.

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  1. Na Li and Yue Guan have contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology, Hebei Medical University, Shijiazhuang, 050017, China

    Na Li, Yue Guan, Yan-Ming Tian, Hui-Jie Ma, Yi Zhang & Sheng Wang

  2. Department of Physiology, Basic Medical College, Hebei University, Baoding, 071000, China

    Na Li

  3. Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, 050000, China

    Yue Guan, Yan-Ming Tian, Hui-Jie Ma, Xiangjian Zhang, Yi Zhang & Sheng Wang

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  1. Na Li
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Li, N., Guan, Y., Tian, YM. et al. Chronic Intermittent Hypobaric Hypoxia Ameliorates Renal Vascular Hypertension Through Up-regulating NOS in Nucleus Tractus Solitarii. Neurosci. Bull. 35, 79–90 (2019). https://doi.org/10.1007/s12264-018-00330-z

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