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Endogenous corticotropin-releasing factor potentiates the excitability of presympathetic neurons in paraventricular nucleus via activation of its receptor 1 in spontaneously hypertensive rats

MA Hong-Yu¹, GUO Xin-Qi¹, ZHAO Qi-Yue¹, YANG Pei-Yun¹, ZHU Huai-Bing¹, GUAN Yue^1,2, ZHANG Yi¹, MA Hui-Jie^1,2,3,*

¹Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China；²Key Laboratory of Neurophysiology of Hebei Province, Shijiazhuang 050017, China；³The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China

Abstract

It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin- releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs. 

Key words: Hypertension; corticotropin-releasing factor; PVN presympathetic neuron; CRF receptor

Received: 　　Accepted:

Corresponding author: 马会杰　　E-mail: huijiema@hebmu.edu.cn

Citing This Article：

MA Hong-Yu, GUO Xin-Qi, ZHAO Qi-Yue, YANG Pei-Yun, ZHU Huai-Bing, GUAN Yue, ZHANG Yi, MA Hui-Jie. Endogenous corticotropin-releasing factor potentiates the excitability of presympathetic neurons in paraventricular nucleus via activation of its receptor 1 in spontaneously hypertensive rats. Acta Physiol Sin 2023; 75 (4): 487-496