Exercise training attenuates hypertension and cardiac hypertrophy by modulating neurotransmitters and cytokines in hypothalamic paraventricular nucleus.
OBJECTIVE
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-κB (NF-κB) p65 and NAD(P)H oxidase in exercise-induced effects.


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 IKKβ, NF-κB 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.


CONCLUSIONS
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-κB and oxidative stress in the PVN may be involved in these exercise-induced effects.
Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China.
Lin-Lin
LL
Jia
Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China.
Yu-Ming
YM
Kang
Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi, China.
Fu-Xin
FX
Wang
Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China.
Hong-Bao
HB
Li
Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China.
Yan
Y
Zhang
Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China.
Xiao-Jing
XJ
Yu
Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China.
Jie
J
Qi
Department of Obstetrics and Gynecology, Shanxi Provincial People's Hospital, Taiyuan, China.
Yu-Ping
YP
Suo
Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China.
Zhen-Jun
ZJ
Tian
Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, The Third Military Medical University, Chongqing Institute of Hypertension, Chongqing, China.
Zhiming
Z
Zhu
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, China.
Guo-Qing
GQ
Zhu
Department of Physiology, Shantou University Medical College, Shantou, China.
Da-Nian
DN
Qin
D000818:Animals; D062186:Arterial Pressure / Q000502:physiology*; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D016207:Cytokines; D016328:NF-kappa B; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D019255:NADPH Oxidases; D009638:Norepinephrine