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Decreased levels of hydrogen sulfide in the hypothalamic paraventricular nucleus contribute to sympathetic hyperactivity induced by cerebral infarction

Hypertension Research volume 47, pages 1323–1337 (2024)Cite this article

Abstract

Paroxysmal sympathetic hyperactivity (PSH) is a common clinical feature secondary to ischemic stroke (IS), but its mechanism is poorly understood. We aimed to investigate the role of H2S in the pathogenesis of PSH. IS patients were divided into malignant (MCI) and non-malignant cerebral infarction (NMCI) group. IS in rats was induced by the right middle cerebral artery occlusion (MCAO). H2S donor (NaHS) or inhibitor (aminooxy-acetic acid, AOAA) were microinjected into the hypothalamic paraventricular nucleus (PVN). Compared with the NMCI group, patients in the MCI group showed PSH, including tachycardia, hypertension, and more plasma norepinephrine (NE) that was positively correlated with levels of creatine kinase, glutamate transaminase, and creatinine respectively. The 1-year survival rate of patients with high plasma NE levels was lower. The hypothalamus of rats with MCAO showed increased activity, especially in the PVN region. The levels of H2S in PVN of the rats with MCAO were reduced, while the blood pressure and renal sympathetic discharge were increased, which could be ameliorated by NaHS and exacerbated by AOAA. NaHS completely reduced the disulfide bond of NMDAR1 in PC12 cells. The inhibition of NMDAR by MK-801 microinjected in PVN of rats with MCAO also could lower blood pressure and renal sympathetic discharge. In conclusion, PSH may be associated with disease progression and survival in patients with IS. Decreased levels of H2S in PVN were involved in regulating sympathetic efferent activity after cerebral infarction. Our results might provide a new strategy and target for the prevention and treatment of PSH.

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Funding

This work is supported by the National Natural Science Foundation of China (32271155, 81770499, 31871154), and the Natural Science Foundation of Hebei [CN] (H2023206367, H2020206350).

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Author notes

  1. These authors contributed equally: Jianping Sun, Yuxin Miao

Authors and Affiliations

  1. Hebei Key Laboratory of Cardiovascular Homeostasis and Aging, Department of Physiology, Hebei Medical University, Shijiazhuang, China

    Jianping Sun, Yuxin Miao, Ping Wang, Qi Guo, Danyang Tian, Hongmei Xue, Lin Xiao, Meng Xu, Ru Wang, Sheng Jin, Xu Teng & Yuming Wu

  2. Department of Neurosurgery, the Second Hospital of Hebei Medical University, Shijiazhuang, China

    Jianping Sun

  3. Hebei Collaborative Innovation Center for Cardio Cerebrovascular Disease, Shijiazhuang, China

    Xiangjian Zhang & Yuming Wu

  4. The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China

    Sheng Jin, Xu Teng & Yuming Wu

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Sun, J., Miao, Y., Wang, P. et al. Decreased levels of hydrogen sulfide in the hypothalamic paraventricular nucleus contribute to sympathetic hyperactivity induced by cerebral infarction. Hypertens Res 47, 1323–1337 (2024). https://doi.org/10.1038/s41440-024-01643-5

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