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Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension.
Toxicol Appl Pharmacol 2014; 279(2):141-9TA

Abstract

The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin-angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague-Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10μg/h) or vehicle via osmotic minipump for 4weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91(phox)) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM.

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 Public Health, 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, Dalian Medical University, Dalian 116044, China.Department of Clinical Laboratory, Sanaitang Hospital, Lanzhou 730030, China.Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, 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

24937322

Citation

Li, Hong-Bao, et al. "Chronic Infusion of Lisinopril Into Hypothalamic Paraventricular Nucleus Modulates Cytokines and Attenuates Oxidative Stress in Rostral Ventrolateral Medulla in Hypertension." Toxicology and Applied Pharmacology, vol. 279, no. 2, 2014, pp. 141-9.
Li HB, Qin DN, Ma L, et al. Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension. Toxicol Appl Pharmacol. 2014;279(2):141-9.
Li, H. B., Qin, D. N., Ma, L., Miao, Y. W., Zhang, D. M., Lu, Y., ... Kang, Y. M. (2014). Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension. Toxicology and Applied Pharmacology, 279(2), pp. 141-9. doi:10.1016/j.taap.2014.06.004.
Li HB, et al. Chronic Infusion of Lisinopril Into Hypothalamic Paraventricular Nucleus Modulates Cytokines and Attenuates Oxidative Stress in Rostral Ventrolateral Medulla in Hypertension. Toxicol Appl Pharmacol. 2014 Sep 1;279(2):141-9. PubMed PMID: 24937322.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension. AU - Li,Hong-Bao, AU - Qin,Da-Nian, AU - Ma,Le, AU - Miao,Yu-Wang, AU - Zhang,Dong-Mei, AU - Lu,Yan, AU - Song,Xin-Ai, AU - Zhu,Guo-Qing, AU - Kang,Yu-Ming, Y1 - 2014/06/14/ PY - 2014/02/02/received PY - 2014/05/07/revised PY - 2014/06/06/accepted PY - 2014/6/18/entrez PY - 2014/6/18/pubmed PY - 2014/10/13/medline KW - Angiotensin-converting enzyme KW - Cytokines KW - Hypertension KW - Hypothalamic paraventricular nucleus KW - Oxidative stress KW - Rostral ventrolateral medulla SP - 141 EP - 9 JF - Toxicology and applied pharmacology JO - Toxicol. Appl. Pharmacol. VL - 279 IS - 2 N2 - The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin-angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague-Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10μg/h) or vehicle via osmotic minipump for 4weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91(phox)) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/24937322/Chronic_infusion_of_lisinopril_into_hypothalamic_paraventricular_nucleus_modulates_cytokines_and_attenuates_oxidative_stress_in_rostral_ventrolateral_medulla_in_hypertension_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(14)00227-0 DB - PRIME DP - Unbound Medicine ER -