title: Exercise training attenuates renovascular hypertension partly via RAS- ROS- glutamate pathway in the hypothalamic paraventricular nucleus.
abstract: Exercise training (ExT) has been reported to benefit hypertension; however, the exact mechanisms involved are unclear. We hypothesized that ExT attenuates hypertension, in part, through the renin-angiotensin system (RAS), reactive oxygen species (ROS), and glutamate in the paraventricular nucleus (PVN). Two-kidney, one-clip (2K1C) renovascular hypertensive rats were assigned to sedentary (Sed) or treadmill running groups for eight weeks. Dizocilpine (MK801), a glutamate receptor blocker, or losartan (Los), an angiotensin II type1 receptor (AT1-R) blocker, were microinjected into the PVN at the end of the experiment. We found that 2K1C rats had higher mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These rats also had excessive oxidative stress and overactivated RAS in PVN. Eight weeks of ExT significantly decreased MAP and RSNA in 2K1C hypertensive rats. ExT inhibited angiotensin-converting enzyme (ACE), AT1-R, and glutamate in the PVN, and angiotensin II (ANG II) in the plasma. Moreover, ExT attenuated ROS by augmenting copper/zinc superoxide dismutase (Cu/Zn-SOD) and decreasing p47phoxand gp91phoxin the PVN. MK801or Los significantly decreased blood pressure in rats. Together, these findings suggest that the beneficial effects of ExT on renovascular hypertension may be, in part, through the RAS-ROS-glutamate pathway in the PVN.
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Yu
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Chen
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Gao
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
authors.forename: Xiao-Lian
authors.initials: XL
authors.lastname: Shi
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Fan
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Jia
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhu
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, 710061, China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Kang
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D000074662:NADPH Oxidase 2 / Q000235:genetics / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D057185:Sedentary Behavior; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D018691:Excitatory Amino Acid Antagonists; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D013482:Superoxide Dismutase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D007703:Peptidyl-Dipeptidase A; D019808:Losartan