Adipose afferent reflex is enhanced by TNFα in paraventricular nucleus through NADPH oxidase-dependent ROS generation in obesity-related hypertensive rats
Abstract Background The adipose afferent reflex (AAR), a sympatho-excitatory reflex, can promote the elevation of sympathetic nerve activity (SNA) and blood pressure (BP). Inflammation in the paraventricular nucleus (PVN) involves sympathetic abnormality in some cardiovascular diseases such as hyper...
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12967-019-2006-0 |
| _version_ | 1818300980165345280 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Lei Ding |
| collection | DOAJ |
| description | Abstract Background The adipose afferent reflex (AAR), a sympatho-excitatory reflex, can promote the elevation of sympathetic nerve activity (SNA) and blood pressure (BP). Inflammation in the paraventricular nucleus (PVN) involves sympathetic abnormality in some cardiovascular diseases such as hypertension. This study was designed to explore the effects of tumor necrosis factor alpha (TNFα) in the PVN on the AAR and SNA in rats with obesity-related hypertension (OH) induced by a high-fat diet for 12 weeks. Methods Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were continuously recorded in anesthetized rats, and their responses to capsaicin (CAP) stimulation of the right inguinal white adipose tissue were used to evaluate the AAR. Results Compared to the control rats, the systolic blood pressure (SBP), plasma norepinephrine (NE, indicating SNA) and TNFα levels, TNFα mRNA and protein levels, reactive oxygen species (ROS) content and NADPH oxidase activity in the PVN were significantly elevated in rats with OH. TNFα in the PVN markedly enhanced sympathoexcitation and AAR. Moreover, the enhancement of AAR caused by TNFα can be significantly strengthened by the pretreatment of diethyldithiocarbamate (DETC), a superoxide dismutase inhibitor, but attenuated by TNF-α receptor antagonist R-7050, superoxide scavenger PEG-SOD and NADPH oxidase inhibitor apocynin (Apo) in rats with OH. Acute microinjection of TNF-α into the PVN significantly increased the activity of NADPH oxidase and ROS levels in rats with OH, which were effectively blocked by R-7050. Furthermore, our results also showed that the increased levels of ROS, TNFα and NADPH oxidase subunits mRNA and protein in the PVN of rats with OH were significantly reversed by pentoxifylline (PTX, 30 mg/kg daily ip; in 10% ethanol) application, a cytokine blocker, for a period of 5 weeks. PTX administration also significantly decreased SBP, AAR and plasma NE levels in rats with OH. Conclusions TNFα in the PVN modulates AAR and contributes to sympathoexcitation in OH possibly through NADPH oxidase-dependent ROS generation. TNFα blockade attenuates AAR and sympathoexcitation that unveils TNFα in the PVN may be a possible therapeutic target for the intervention of OH. |
| first_indexed | 2024-12-13T05:15:44Z |
| format | Article |
| id | doaj.art-96e501e1053645c4abc1a97ca821ce6b |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-13T05:15:44Z |
| publishDate | 2019-08-01 |
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| spelling | doaj.art-96e501e1053645c4abc1a97ca821ce6b2022-12-21T23:58:26ZengBMCJournal of Translational Medicine1479-58762019-08-0117111310.1186/s12967-019-2006-0Adipose afferent reflex is enhanced by TNFα in paraventricular nucleus through NADPH oxidase-dependent ROS generation in obesity-related hypertensive ratsLei Ding0Ying Kang1Hang-Bing Dai2Fang-Zheng Wang3Hong Zhou4Qing Gao5Xiao-Qing Xiong6Feng Zhang7Tian-Run Song8Yan Yuan9Ming Liu10Guo-Qing Zhu11Ye-Bo Zhou12Department of Physiology, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityDepartment of Physiology, Nanjing Medical UniversityAbstract Background The adipose afferent reflex (AAR), a sympatho-excitatory reflex, can promote the elevation of sympathetic nerve activity (SNA) and blood pressure (BP). Inflammation in the paraventricular nucleus (PVN) involves sympathetic abnormality in some cardiovascular diseases such as hypertension. This study was designed to explore the effects of tumor necrosis factor alpha (TNFα) in the PVN on the AAR and SNA in rats with obesity-related hypertension (OH) induced by a high-fat diet for 12 weeks. Methods Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were continuously recorded in anesthetized rats, and their responses to capsaicin (CAP) stimulation of the right inguinal white adipose tissue were used to evaluate the AAR. Results Compared to the control rats, the systolic blood pressure (SBP), plasma norepinephrine (NE, indicating SNA) and TNFα levels, TNFα mRNA and protein levels, reactive oxygen species (ROS) content and NADPH oxidase activity in the PVN were significantly elevated in rats with OH. TNFα in the PVN markedly enhanced sympathoexcitation and AAR. Moreover, the enhancement of AAR caused by TNFα can be significantly strengthened by the pretreatment of diethyldithiocarbamate (DETC), a superoxide dismutase inhibitor, but attenuated by TNF-α receptor antagonist R-7050, superoxide scavenger PEG-SOD and NADPH oxidase inhibitor apocynin (Apo) in rats with OH. Acute microinjection of TNF-α into the PVN significantly increased the activity of NADPH oxidase and ROS levels in rats with OH, which were effectively blocked by R-7050. Furthermore, our results also showed that the increased levels of ROS, TNFα and NADPH oxidase subunits mRNA and protein in the PVN of rats with OH were significantly reversed by pentoxifylline (PTX, 30 mg/kg daily ip; in 10% ethanol) application, a cytokine blocker, for a period of 5 weeks. PTX administration also significantly decreased SBP, AAR and plasma NE levels in rats with OH. Conclusions TNFα in the PVN modulates AAR and contributes to sympathoexcitation in OH possibly through NADPH oxidase-dependent ROS generation. TNFα blockade attenuates AAR and sympathoexcitation that unveils TNFα in the PVN may be a possible therapeutic target for the intervention of OH.http://link.springer.com/article/10.1186/s12967-019-2006-0Adipose afferent reflexTNFαParaventricular nucleusSympathoexcitationObesityReactive oxygen species |
| spellingShingle | 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 Adipose afferent reflex is enhanced by TNFα in paraventricular nucleus through NADPH oxidase-dependent ROS generation in obesity-related hypertensive rats Journal of Translational Medicine Adipose afferent reflex TNFα Paraventricular nucleus Sympathoexcitation Obesity Reactive oxygen species |
| title | Adipose afferent reflex is enhanced by TNFα in paraventricular nucleus through NADPH oxidase-dependent ROS generation in obesity-related hypertensive rats |
| title_full | Adipose afferent reflex is enhanced by TNFα in paraventricular nucleus through NADPH oxidase-dependent ROS generation in obesity-related hypertensive rats |
| title_fullStr | Adipose afferent reflex is enhanced by TNFα in paraventricular nucleus through NADPH oxidase-dependent ROS generation in obesity-related hypertensive rats |
| title_full_unstemmed | Adipose afferent reflex is enhanced by TNFα in paraventricular nucleus through NADPH oxidase-dependent ROS generation in obesity-related hypertensive rats |
| title_short | Adipose afferent reflex is enhanced by TNFα in paraventricular nucleus through NADPH oxidase-dependent ROS generation in obesity-related hypertensive rats |
| title_sort | adipose afferent reflex is enhanced by tnfα in paraventricular nucleus through nadph oxidase dependent ros generation in obesity related hypertensive rats |
| topic | Adipose afferent reflex TNFα Paraventricular nucleus Sympathoexcitation Obesity Reactive oxygen species |
| url | http://link.springer.com/article/10.1186/s12967-019-2006-0 |
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