title: Chronic vagus nerve stimulation attenuates vascular endothelial impairments and reduces the inflammatory profile via inhibition of the NF-κB signaling pathway in ovariectomized rats.
abstract: Vagus nerve stimulation (VNS), a method for activating cholinergic anti-inflammatory pathways, could suppress endothelial activation and minimize tissue injury during inflammation. The aim of this study was to investigate the effects of chronic VNS on endothelial impairments and the inflammatory profile in ovariectomized (OVX) rats. Sprague-Dawley rats (7-8 months old) were randomly assigned to the following four groups: sham-OVX, OVX, OVX+sham-VNS, and OVX+VNS. Throughout the experimental period, the OVX+VNS group received VNS for 3h (20.0 Hz, 1.0 mA, and 10.00 ms pulse width) at the same time every other day. After 12 weeks of VNS, blood samples and thoracic aortas were collected for further analyses. Light microscopy and electron microscopy analyses showed that chronic VNS prevented endothelial swelling, desquamation and even necrosis in the OVX rats. In addition, it obviously improved endothelial function in the OVX rats by restoring the endothelial nitric oxide synthase (e-NOS) and serum endothelin-1 level. Increased expression of cell adhesion molecules (VCAM-1, ICAM-1 and E-selectin) in the thoracic aortas and increases in the levels of circulating cytokines (TNF-α, IL-6, MCP-1, and CINC/KC) were also observed in the OVX rats. Chronic VNS significantly restored these detrimental changes partly by increasing the ACh concentrations in vascular walls and blocking NF-κB pathway activity. The results of this in vivo study have shown that the administration of chronic VNS during, in the early stage of estrogen deficiency, protects OVX rats from endothelial impairments and the inflammatory profile. These findings indicate that activation of the vagus nerve could be a promising supplemental therapy for reducing the risks of suffering from further CVDs in postmenopausal women.
authors.affiliation: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Cardiothoracic Surgery, Shenzhen Children's Hospital, Shenzhen, People's Republic of China.
authors.forename: Huaipu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China. Electronic address: wangth@mail.sysu.edu.cn.
authors.forename: Tinghuai
authors.initials: T
authors.lastname: Wang
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D005260:Female; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010052:Ovariectomy; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D055536:Vagus Nerve Stimulation; D014664:Vasodilation
chemical_list: D015815:Cell Adhesion Molecules; D018836:Inflammation Mediators; D016328:NF-kappa B; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine
keywords: Cholinergic anti-inflammatory pathway; Chronic vagus nerve stimulation; Endothelial dysfunction; Inflammation; Ovariectomy