1. Academic Validation
  2. Interleukin-1β in hypothalamic paraventricular nucleus mediates excitatory renal reflex

Interleukin-1β in hypothalamic paraventricular nucleus mediates excitatory renal reflex

  • Pflugers Arch. 2020 Nov;472(11):1577-1586. doi: 10.1007/s00424-020-02461-7.
Fen Zheng 1 Chao Ye 1 Guo-Wei Wan 1 Bing Zhou 1 Ying Tong 1 Jian-Zhen Lei 1 Qi Chen 2 Yue-Hua Li 2 Yu-Ming Kang 3 Guo-Qing Zhu 4 5
Affiliations

Affiliations

  • 1 Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.
  • 2 Department of Pathophysiology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.
  • 3 Department of Physiology and Pathophysiology, Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, 710061, China.
  • 4 Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. gqzhucn@njmu.edu.cn.
  • 5 Department of Pathophysiology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. gqzhucn@njmu.edu.cn.
Abstract

Chemical stimulation of kidney causes sympathetic activation and pressor responses in rats. The excitatory renal reflex (ERR) is mediated by angiotensin type 1 receptor (AT1R) and superoxide anions in hypothalamic paraventricular nucleus (PVN). The aim of this study is to determine whether interleukin-1β (IL-1β) in the PVN mediates the ERR, and whether the IL-1β production in the PVN is dependent on the AT1R-superoxide anion signaling. Experiments were performed in adult rats under anesthesia. The ERR was induced by renal infusion of capsaicin, and evaluated by the responses of the contralateral renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP). Inhibition of IL-1β production with MCC950 in the PVN dose-dependently inhibited the capsaicin-induced ERR and sympathetic activation. The PVN microinjection of IL-1 receptor antagonist IL-1RA or specific IL-1β antibody abolished the capsaicin-induced ERR, while IL-1β enhanced the ERR. Renal infusion of capsaicin promoted p65-NFκB phosphorylation and IL-1β production in the PVN, which were prevented by PVN microinjection of NADPH Oxidase Inhibitor apocynin or the superoxide anion scavenger tempol. The PVN microinjection of NFκB inhibitor BMS-345541 abolished the capsaicin induced-ERR and IL-1β production, but not the NADPH Oxidase activation and superoxide anion production. Furthermore, capsaicin-induced p65-NFκB phosphorylation and IL-1β production in the PVN were prevented by AT1R antagonist losartan, or angiotensin converting Enzyme inhibitor captopril. These results indicate that capsaicin-induced ERR and sympathetic activation are mediated by IL-1β in the PVN. The IL-1β production in the PVN is dependent on the AT1R-mediated superoxide anion generation and NFκB activation.

Keywords

Angiotensin; Blood pressure; Interleukin; Reactive oxygen species; Renal reflex; Sympathetic activity.

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