Adipose afferent reflex is enhanced by TNFα in paraventricular nucleus through NADPH oxidase-dependent ROS generation in obesity-related hypertensive rats

• DOI: 10.1186/s12967-019-2006-0
• Publication Date: 2019-08-07T12:02:53Z
• Authors: Lei Ding; Ying Kang; Hang-Bing Dai; Fang-Zheng Wang; Hong Zhou; Qing Gao; Xiao-Qing Xiong; Feng Zhang; Tian-Run Song; Yan Yuan; Ming Liu; Guo-Qing Zhu; Ye-Bo Zhou
• Keywords: Male; 0301 basic medicine; Sympathetic Nervous System; Systole; Adipose Tissue, White; Diet, High-Fat; Rats, Sprague-Dawley; Norepinephrine; 03 medical and health sciences; Rats, Inbred SHR; Paraventricular nucleus; Adipose afferent reflex; TNFα; Animals; Neurons, Afferent; Obesity; Adiposity; Inflammation; 2. Zero hunger; Tumor Necrosis Factor-alpha; Research; Body Weight; R; NADPH Oxidases; Rats; 3. Good health; Sympathoexcitation; Adipose Tissue; Medicine; Reactive oxygen species; Reactive Oxygen Species; Paraventricular Hypothalamic Nucleus

The adipose afferent reflex (AAR), a sympatho-excitatory reflex, can promote the elevation of sympathetic nerve activity (SNA) and blood pressure (BP). Inflammation in paraventricular nucleus (PVN) involves abnormality some cardiovascular diseases such as hypertension. This study was designed to explore effects tumor necrosis factor alpha (TNFα) PVN on AAR SNA rats with obesity-related hypertension (OH) induced by high-fat diet for 12 weeks. Renal (RSNA) mean arterial (MAP) were continuously recorded anesthetized rats, their responses capsaicin (CAP) stimulation right inguinal white tissue used evaluate AAR. Compared control systolic (SBP), plasma norepinephrine (NE, indicating SNA) TNFα levels, mRNA protein reactive oxygen species (ROS) content NADPH oxidase significantly elevated OH. markedly enhanced sympathoexcitation Moreover, enhancement caused be strengthened pretreatment diethyldithiocarbamate (DETC), superoxide dismutase inhibitor, but attenuated TNF-α receptor antagonist R-7050, scavenger PEG-SOD inhibitor apocynin (Apo) Acute microinjection into increased ROS levels OH, which effectively blocked R-7050. Furthermore, our results also showed that ROS, subunits OH reversed pentoxifylline (PTX, 30 mg/kg daily ip; 10% ethanol) application, cytokine blocker, period 5 PTX administration decreased SBP, NE modulates contributes possibly through oxidase-dependent generation. blockade attenuates unveils may possible therapeutic target intervention