Blockade of PVN neuromedin B receptor alleviates inflammation via the RAS/ROS/NF-κB pathway in spontaneously hypertensive rats
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,...
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Elsevier
2025-01-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923024003149 |
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| author | Kai-Li Liu Tian-Ze Sun Yu Yang Qian-Xi Gao Li-Mei Tu Jia-Yue Yu Qiao-Zhen Tian Li-Yan Fu Shu-Huan Tang Hong-Li Gao Jie Qi Yu-Ming Kang Xiao-Jing Yu |
| author_facet | Kai-Li Liu Tian-Ze Sun Yu Yang Qian-Xi Gao Li-Mei Tu Jia-Yue Yu Qiao-Zhen Tian Li-Yan Fu Shu-Huan Tang Hong-Li Gao Jie Qi Yu-Ming Kang Xiao-Jing Yu |
| author_sort | Kai-Li Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-80383d57ba8143a09b70ba6110fbfc6a |
| institution | OA Journals |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Brain Research Bulletin |
| spelling | doaj-art-80383d57ba8143a09b70ba6110fbfc6a2025-08-20T02:27:40ZengElsevierBrain Research Bulletin1873-27472025-01-0122011118010.1016/j.brainresbull.2024.111180Blockade of PVN neuromedin B receptor alleviates inflammation via the RAS/ROS/NF-κB pathway in spontaneously hypertensive ratsKai-Li Liu0Tian-Ze Sun1Yu Yang2Qian-Xi Gao3Li-Mei Tu4Jia-Yue Yu5Qiao-Zhen Tian6Li-Yan Fu7Shu-Huan Tang8Hong-Li Gao9Jie Qi10Yu-Ming Kang11Xiao-Jing Yu12Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, ChinaDepartment of Medical Imaging, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, ChinaDepartment of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, China; Department of Pharmacology, School of Basic Medical Sciences, Jiamusi University, Jiamusi 154007, ChinaDepartment of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, China; Shanxi Medical University, Taiyuan 030001, ChinaDepartment of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, China; Shanxi Medical University, Taiyuan 030001, ChinaDepartment of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, ChinaDepartment of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, China; Shanxi Datong University, Datong 037009, ChinaDepartment of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, ChinaDepartment of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, ChinaDepartment of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, ChinaDepartment of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, ChinaDepartment of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, ChinaDepartment of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S0361923024003149Neuromedin B receptorPVNInflammationRAS/ROS/ NF-κB pathwayHypertension |
| spellingShingle | Kai-Li Liu Tian-Ze Sun Yu Yang Qian-Xi Gao Li-Mei Tu Jia-Yue Yu Qiao-Zhen Tian Li-Yan Fu Shu-Huan Tang Hong-Li Gao Jie Qi Yu-Ming Kang Xiao-Jing Yu Blockade of PVN neuromedin B receptor alleviates inflammation via the RAS/ROS/NF-κB pathway in spontaneously hypertensive rats Brain Research Bulletin Neuromedin B receptor PVN Inflammation RAS/ROS/ NF-κB pathway Hypertension |
| title | Blockade of PVN neuromedin B receptor alleviates inflammation via the RAS/ROS/NF-κB pathway in spontaneously hypertensive rats |
| title_full | Blockade of PVN neuromedin B receptor alleviates inflammation via the RAS/ROS/NF-κB pathway in spontaneously hypertensive rats |
| title_fullStr | Blockade of PVN neuromedin B receptor alleviates inflammation via the RAS/ROS/NF-κB pathway in spontaneously hypertensive rats |
| title_full_unstemmed | Blockade of PVN neuromedin B receptor alleviates inflammation via the RAS/ROS/NF-κB pathway in spontaneously hypertensive rats |
| title_short | Blockade of PVN neuromedin B receptor alleviates inflammation via the RAS/ROS/NF-κB pathway in spontaneously hypertensive rats |
| title_sort | blockade of pvn neuromedin b receptor alleviates inflammation via the ras ros nf κb pathway in spontaneously hypertensive rats |
| topic | Neuromedin B receptor PVN Inflammation RAS/ROS/ NF-κB pathway Hypertension |
| url | http://www.sciencedirect.com/science/article/pii/S0361923024003149 |
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