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Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system and proinflammatory cytokines in hypertension.
Toxicol Appl Pharmacol 2014; 276(2):115-20TA

Abstract

AIMS

To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin-angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension.

METHODS AND RESULTS

Male Sprague-Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91(phox) (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1 beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91(phox), ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats.

CONCLUSION

These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension.

Authors+Show Affiliations

Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.Department of Physiology, Shantou University Medical College, Shantou 515041, China. Electronic address: dnqin@stu.edu.cn.Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi 154002, China.Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA.Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, The Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China. Electronic address: ykang@mail.xjtu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24576725

Citation

Su, Qing, et al. "Inhibition of Reactive Oxygen Species in Hypothalamic Paraventricular Nucleus Attenuates the Renin-angiotensin System and Proinflammatory Cytokines in Hypertension." Toxicology and Applied Pharmacology, vol. 276, no. 2, 2014, pp. 115-20.
Su Q, Qin DN, Wang FX, et al. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system and proinflammatory cytokines in hypertension. Toxicol Appl Pharmacol. 2014;276(2):115-20.
Su, Q., Qin, D. N., Wang, F. X., Ren, J., Li, H. B., Zhang, M., ... Kang, Y. M. (2014). Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system and proinflammatory cytokines in hypertension. Toxicology and Applied Pharmacology, 276(2), pp. 115-20. doi:10.1016/j.taap.2014.02.002.
Su Q, et al. Inhibition of Reactive Oxygen Species in Hypothalamic Paraventricular Nucleus Attenuates the Renin-angiotensin System and Proinflammatory Cytokines in Hypertension. Toxicol Appl Pharmacol. 2014 Apr 15;276(2):115-20. PubMed PMID: 24576725.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system and proinflammatory cytokines in hypertension. AU - Su,Qing, AU - Qin,Da-Nian, AU - Wang,Fu-Xin, AU - Ren,Jun, AU - Li,Hong-Bao, AU - Zhang,Meng, AU - Yang,Qing, AU - Miao,Yu-Wang, AU - Yu,Xiao-Jing, AU - Qi,Jie, AU - Zhu,Zhiming, AU - Zhu,Guo-Qing, AU - Kang,Yu-Ming, Y1 - 2014/02/25/ PY - 2013/10/26/received PY - 2014/02/06/revised PY - 2014/02/08/accepted PY - 2014/3/1/entrez PY - 2014/3/1/pubmed PY - 2014/5/31/medline KW - Hypertension KW - Hypothalamic paraventricular nucleus KW - Oxidative stress KW - Proinflammatory cytokines KW - Renin–angiotensin system SP - 115 EP - 20 JF - Toxicology and applied pharmacology JO - Toxicol. Appl. Pharmacol. VL - 276 IS - 2 N2 - AIMS: To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin-angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension. METHODS AND RESULTS: Male Sprague-Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91(phox) (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1 beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91(phox), ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats. CONCLUSION: These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/24576725/Inhibition_of_reactive_oxygen_species_in_hypothalamic_paraventricular_nucleus_attenuates_the_renin_angiotensin_system_and_proinflammatory_cytokines_in_hypertension_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(14)00039-8 DB - PRIME DP - Unbound Medicine ER -