PMID- 24482680 OWN - NLM STAT- MEDLINE DCOM- 20150123 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 1 DP - 2014 TI - Exercise training attenuates hypertension and cardiac hypertrophy by modulating neurotransmitters and cytokines in hypothalamic paraventricular nucleus. PG - e85481 LID - 10.1371/journal.pone.0085481 [doi] LID - e85481 AB - AIMS: Regular exercise as an effective non-pharmacological antihypertensive therapy is beneficial for prevention and control of hypertension, but the central mechanisms are unclear. In this study, we hypothesized that chronic exercise training (ExT) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs) and restoring the neurotransmitters balance in the hypothalamic paraventricular nucleus (PVN) in young spontaneously hypertensive rats (SHR). In addition, we also investigated the involvement of nuclear factor-kappaB (NF-kappaB) p65 and NAD(P)H oxidase in exercise-induced effects. METHODS AND RESULTS: Moderate-intensity ExT was administrated to young normotensive Wistar-Kyoto (WKY) and SHR rats for 16 weeks. SHR rats had a significant increase in mean arterial pressure and cardiac hypertrophy. SHR rats also had higher levels of glutamate, norepinephrine (NE), phosphorylated IKKbeta, NF-kappaB p65 activity, NAD(P)H oxidase subunit gp91(phox), PICs and the monocyte chemokine protein-1 (MCP-1), and lower levels of gamma-aminobutyric acid (GABA) and interleukin-10 (IL-10) in the PVN. These SHR rats also exhibited higher renal sympathetic nerve activity (RSNA), and higher plasma levels of PICs, and lower plasma IL-10. However, ExT ameliorates all these changes in SHR rats. CONCLUSION: These findings suggest that there are the imbalances between excitatory and inhibitory neurotransmitters and between pro- and anti-inflammatory cytokines in the PVN of SHR rats, which at least partly contributing to sympathoexcitation, hypertension and cardiac hypertrophy; chronic exercise training attenuates hypertension and cardiac hypertrophy by restoring the balances between excitatory and inhibitory neurotransmitters and between pro- and anti-inflammatory cytokines in the PVN; NF-kappaB and oxidative stress in the PVN may be involved in these exercise-induced effects. FAU - Jia, Lin-Lin AU - Jia LL AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China. FAU - Kang, Yu-Ming AU - Kang YM AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China. FAU - Wang, Fu-Xin AU - Wang FX AD - Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi, China. FAU - Li, Hong-Bao AU - Li HB AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China. FAU - Zhang, Yan AU - Zhang Y AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China. FAU - Yu, Xiao-Jing AU - Yu XJ AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China. FAU - Qi, Jie AU - Qi J AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China. FAU - Suo, Yu-Ping AU - Suo YP AD - Department of Obstetrics and Gynecology, Shanxi Provincial People's Hospital, Taiyuan, China. FAU - Tian, Zhen-Jun AU - Tian ZJ AD - Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China. FAU - Zhu, Zhiming AU - Zhu Z AD - Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, The Third Military Medical University, Chongqing Institute of Hypertension, Chongqing, China. FAU - Zhu, Guo-Qing AU - Zhu GQ AD - Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, China. FAU - Qin, Da-Nian AU - Qin DN AD - Department of Physiology, Shantou University Medical College, Shantou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140117 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 3KX376GY7L (Glutamic Acid) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - EC 1.6.3.- (NADPH Oxidases) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Animals MH - Arterial Pressure/*physiology MH - Cardiomegaly/metabolism/physiopathology/*therapy MH - Cytokines/*metabolism MH - Glutamic Acid/metabolism MH - Hypertension/metabolism/physiopathology/*therapy MH - Male MH - NADPH Oxidases/metabolism MH - NF-kappa B/metabolism MH - Norepinephrine/metabolism MH - Oxidative Stress/physiology MH - Paraventricular Hypothalamic Nucleus/*metabolism MH - Physical Conditioning, Animal/*physiology MH - Rats MH - Rats, Inbred SHR MH - Rats, Inbred WKY MH - Sympathetic Nervous System/metabolism/physiopathology MH - gamma-Aminobutyric Acid/metabolism PMC - PMC3901693 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/02/01 06:00 MHDA- 2015/01/24 06:00 PMCR- 2014/01/17 CRDT- 2014/02/01 06:00 PHST- 2013/09/02 00:00 [received] PHST- 2013/11/28 00:00 [accepted] PHST- 2014/02/01 06:00 [entrez] PHST- 2014/02/01 06:00 [pubmed] PHST- 2015/01/24 06:00 [medline] PHST- 2014/01/17 00:00 [pmc-release] AID - PONE-D-13-36121 [pii] AID - 10.1371/journal.pone.0085481 [doi] PST - epublish SO - PLoS One. 2014 Jan 17;9(1):e85481. doi: 10.1371/journal.pone.0085481. eCollection 2014.