Blockade of PVN neuromedin B receptor alleviates inflammation via the RAS/ROS/NF-κB pathway in spontaneously hypertensive rats

• Published in: Brain research bulletin 2025-01, Vol.220, p.111180, Article 111180
• Main Authors: Liu, Kai-Li, Sun, Tian-Ze, Yang, Yu, Gao, Qian-Xi, Tu, Li-Mei, Yu, Jia-Yue, Tian, Qiao-Zhen, Fu, Li-Yan, Tang, Shu-Huan, Gao, Hong-Li, Qi, Jie, Kang, Yu-Ming, Yu, Xiao-Jing
• Format: Article
• Language: English
• Subjects: Hypertension; Inflammation; Neuromedin B receptor; PVN; RAS/ROS/ NF-κB pathway
• ISSN: 0361-9230; 1873-2747; 1873-2747
• DOI: 10.1016/j.brainresbull.2024.111180

Neuromedin B (NMB) has potentially great impacts on the development of cardiovascular diseases by promoting hypertensive and sympatho-excitation effects. However, studies regarding the NMB function in paraventricular nucleus (PVN) are lacking. With selective neuromedin B receptor (NMBR) antagonist, BIM-23127, we aim to determine whether the blockade of NMB function in PVN could alleviate central inflammation and attenuate hypertensive responses. Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were chronically infused with BIM-23127 in the PVN for 6 weeks. Mean arterial pressure (MAP) was assessed with tail cuff and electrophysiological acquisition systems. PVN tissues were collected to analyze expressions of Fra-LI, inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-10, and IL-4), renin-angiotensin system (angiotensin-converting enzyme (ACE), ACE2, and AT1-reporter (AT1-R)) and oxidative stress (reactive oxygen species (ROS), superoxide dismutase (SOD)1, NADPH oxidase (NOX)2, and NOX4). ELISA was used to detect inflammation indices, norepinephrine (NE), and nuclear factor κB (NF-κB) p65 in plasma and PVN tissue homogenate. Compared to WKY, SHR exhibited higher mean arterial pressure (MAP), plasma NE, and pro-inflammatory cytokines (PICs). Higher PVN levels of Fra-LI, PICs, ACE, AT1-R, ROS, NOX2, NOX4, and NF-κB p65, while lower central levels of anti-inflammatory cytokines (AICs), ACE2, and SOD1 were observed in SHR. Administration of BIM-23127 in PVN reversed all these changes in SHR. In SHR, blockade of NMBR in the PVN inhibited sympatho-excitation and attenuated hypertensive response. The attenuation mechanism may involve reducing inflammation and the RAS/ROS/ NF-κB pathways in PVN. [Display omitted] •The effect of chronic infusion of neuromedin B receptor blocker in PVN on spontaneous hypertension is reported.•PVN blockade of neuromedin B receptor attenuates hypertension and sympathoexcitation.•PVN blockade of neuromedin B receptor alleviates PVN inflammation through RAS/ROS/NF-κB signaling pathways.