Aerobic exercise inhibits sympathetic nerve sprouting and restores β-adrenergic receptor balance in rats with myocardial infarction.
BACKGROUND
Cardiac sympathetic nerve sprouting and the dysregulation of β-adrenergic receptor (β-AR) play a critical role in the deterioration of cardiac function after myocardial infarction (MI). Growing evidence indicates that exercise provides protection against MI. The aims of this study were to investigate whether aerobic exercise following MI could inhibit sympathetic nerve sprouting and restore the balance of β3-AR/β1-AR.


METHODS
Male Sprague-Dawley rats were divided into three groups: sham-operated control group (SC), MI group (MI), and MI with aerobic exercise group (ME). The rats in ME group were assigned to 8 weeks of exercise protocol (16 m/min, 50 min/d, 5 d/wk). The expression of nerve growth factor (NGF), the sympathetic nerve marker-tyrosine hydroxylase (TH), the nerve sprouting marker-growth associated protein 43 (GAP43), and β1- and β2-AR expression in the peri-infarct area of the left ventricle (LV) were measured by Western blot and immunohistochemistry, while β3-AR expression was determined by Western blot and immunofluorescence. Endothelial nitric oxide synthase (NOS2), phospho-NOS2 (p-NOS2), and neuronal nitric oxide synthase (NOS1) were measured by Western blot.


RESULTS
MI increased LV end-diastolic pressure (LVEDP), and decreased LV systolic pressure (LVSP). Compared with the MI group, aerobic exercise significantly decreased LVEDP and increased LVSP. The protein expression of TH, GAP43 and NGF was significantly increased after MI, which was normalized by exercise. Compared with the SC group, the ratios of β2-AR/β1-AR and β3-AR/β1-AR were elevated in the MI group, and the protein expression of β3-AR and NOS1 increased after MI. Compared with the MI group, the ratios of β2-AR/β1-AR and β3-AR/β1-AR were normalized in the ME group, while the protein expression of β3-AR and NOS1 significantly increased, and NOS2 was activated by exercise.


CONCLUSIONS
Aerobic exercise inhibits cardiac sympathetic nerve sprouting, restores β3-AR/β1-AR balance and increases β3-AR expression through the activation of NOS2 and NOS1 after myocardial infarction.
Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, P. R. China; Department of Sports and Exercise, Tibet University for Nationalities, Xian yang, Shaanxi, P. R. China.
Ting
T
Chen
Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, P. R. China.
Meng-Xin
MX
Cai
Department of Physiology and Department of Cardiology, Fourth Military Medical University, Xi'an, Shaanxi, P. R. China.
You-You
YY
Li
Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, P. R. China.
Zhi-Xiong
ZX
He
Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, P. R. China.
Xiu-Chao
XC
Shi
Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, P. R. China.
Wei
W
Song
Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, P. R. China.
You-Hua
YH
Wang
Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, P. R. China.
Yue
Y
Xi
Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, P. R. China.
Yu-Ming
YM
Kang
Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, P. R. China.
Zhen-Jun
ZJ
Tian
D000818:Animals; D015153:Blotting, Western; D005081:Exercise Therapy / Q000379:methods*; D005455:Fluorescent Antibody Technique; D019922:GAP-43 Protein / Q000378:metabolism; D006439:Hemodynamics; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D020932:Nerve Growth Factor / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D019922:GAP-43 Protein; D011943:Receptors, Adrenergic, beta; D020932:Nerve Growth Factor; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; D014446:Tyrosine 3-Monooxygenase