Hua Tian1, Yu-Ming Kang2, Hong-Li Gao2, Xiao-Lian Shi3, Li-Yan Fu2, Ying Li2, Xiu-Yue Jia2, Kai-Li Liu2, Jie Qi2, Hong-Bao Li2, Yan-Mei Chen2, Wen-Sheng Chen4, Wei Cui5, Guo-Qing Zhu6, Xiao-Jing Yu7. 1. Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University, Xi'an 710061, China; Department of Diagnosis, Shaanxi University of Chinese Medicine Xi'an, 712046, China. 2. Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University, Xi'an 710061, China. 3. Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. 4. Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. 5. Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. 6. Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China. 7. Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: yuxiaojing@mail.xjtu.edu.cn.
Abstract
BACKGROUND: Berberine (BBR), a Chinese traditional herbal medicine, has many pharmacologic benefits such as anti-inflammation and anti-oxidation. It is widely used in clinical treatment of cardiovascular diseases such as hypertension. However, the mechanism of how BBR attenuates hypertension through affecting central neural system is not clear. PURPOSE: This study was designed to determine whether chronic infusion of BBR into the hypothalamic paraventricular nucleus (PVN) attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway. METHODS: Two-kidney, one-clip (2K1C) renovascular hypertensive rats were randomly assigned and treated with bilateral PVN infusion of BBR (2μg/h) or vehicle (artificial cerebrospinal fluid) via osmotic minipumps for 28 days. RESULTS: 2K1C rats showed higher mean arterial pressure (MAP) and PVN Fra-like activity, plasma levels of norepinephrine (NE), PVN levels of NOX2, NOX4, Erk1/2 and iNOS, and lower PVN levels of copper/zinc superoxide dismutase (Cu/Zn-SOD). Chronic infusion of BBR reduced MAP, PVN Fra-like activity and plasma levels of NE, reduced NOX2, NOX4, Erk1/2, iNOS and induced Cu/Zn-SOD in the PVN. CONCLUSIONS: These results suggest that BBR attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway in 2K1C renovascular hypertensive rats.
BACKGROUND:Berberine (BBR), a Chinese traditional herbal medicine, has many pharmacologic benefits such as anti-inflammation and anti-oxidation. It is widely used in clinical treatment of cardiovascular diseases such as hypertension. However, the mechanism of how BBR attenuates hypertension through affecting central neural system is not clear. PURPOSE: This study was designed to determine whether chronic infusion of BBR into the hypothalamic paraventricular nucleus (PVN) attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway. METHODS: Two-kidney, one-clip (2K1C) renovascular hypertensiverats were randomly assigned and treated with bilateral PVN infusion of BBR (2μg/h) or vehicle (artificial cerebrospinal fluid) via osmotic minipumps for 28 days. RESULTS: 2K1C rats showed higher mean arterial pressure (MAP) and PVN Fra-like activity, plasma levels of norepinephrine (NE), PVN levels of NOX2, NOX4, Erk1/2 and iNOS, and lower PVN levels of copper/zinc superoxide dismutase (Cu/Zn-SOD). Chronic infusion of BBR reduced MAP, PVN Fra-like activity and plasma levels of NE, reduced NOX2, NOX4, Erk1/2, iNOS and induced Cu/Zn-SOD in the PVN. CONCLUSIONS: These results suggest that BBR attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway in 2K1C renovascular hypertensiverats.
Authors: Alexa S Hendricks; Matthew J Lawson; Jorge P Figueroa; Mark C Chappell; Debra I Diz; Hossam A Shaltout Journal: Am J Physiol Heart Circ Physiol Date: 2019-04-05 Impact factor: 4.733