Effect of Aerobic Exercise on Plasma Catecholamine in Rats with Heart Failure and Its Mechanisms
【Abstract】Objective: To observe the effect of aerobic exercise on adrenal G protein-coupled receptor kinase-2 (GRK2), α2-adrenergic receptor (α2-AR) and plasma catecholamine in rats with heart failure and to investigate the possible mechanism of exercise-induced inhibition on excessive activation of sympathetic nerve. Methods: Thirty six healthy male Wistar rats were randomly divided into sham-operation sedentary group (SF-sed group), heartfailure sedentary control group (HF-sed group), and heart-failure exercise group (HF-ex group). Rats in HF-ex group finished 10-week treadmill training while rats of SH-sed and HF-sed groups kept resting state. After the experiment, cardiac structure and function were detected by ultrechocardiograph; collagen volume fraction (CVF) was tested by Masson staining; plasma epinephrine (EP) and norepinephrine (NEP) were measured by high pressure liquid chromatography; mRNA of cardiac collagen type I (Col-1), atrial natriuretic factor (ANF), and transforming growth factor-β1 (TGF-β1) was tested by real-time quantitative PCR and the protein level of adrenal GRK2 and α2-AR was explored by Western blotting. Results: 1) Compared with SH-sed group, fractional shortening (FS) and left ventricular ejection fraction (LVEF) in HF-sed group were decreased (P < 0.05) and plasma EP and NEPwas increased (P < 0.05); mRNA expression of heart Col-1, ANF and TGF-β1 (remodeling genes) and protein of adrenal GRK2 were upregulated (P < 0.05),while adrenal α2-AR protein was downregulated (P < 0.05).
【Keywords】 aerobic exercise; heart failure; rats; catecholamine; sympathetic nerve;
(Translated by PXJ1)
 SEO Y, NAKATSUKASA T, SAI S, et al. Clinical implications of organ congestion in heart failure patients as assessed by ultrasonography. Cardiovasc Diagn Ther, 2018, 8 (1): 57–69.
 SPADARI RC, CAVADAS C, DE CARVALHO AETS, et al. Role of beta-adrenergic receptors and sirtuin signaling in the heart during aging, heart failure, and adaptation to stress. Cell Mol Neurobiol, 2018, 38 (1): 109–120.
 PEARSON MJ, SMART NA. Exercise therapy and autonomic function in heart failure patients: a systematic review and meta-analysis. Heart Fail Rev, 2018, 23 (1): 91–108.
 Zhou, Y. & Li, X. China Sport Science (体育科学), 32 (3): 67–73 (2012).
 LYMPEROPOULOS A, RENGO G, FUNAKOSHI H, et al. Adrenal GRK2 upregulation mediates sympathetic overdrive in heart failure. Nat Med, 2007, 13 (3): 315–323.
 RENGO G, LYMPEROPOULOS A, ZINCARELLI C, et al. Blockade of β-adrenoceptors restores the GRK2-mediated adrenal α (2)-adrenoceptor-catecholamine production axis in heart failure. Br J Pharmacol, 2012, 166 (8): 2430–2440.
 Li, X., Jiang, M. Liu, Z. et al. Journal of Shanghai University of Sport (上海体育学院学报), 39 (5): 38–43 (2015).
 Li, X., Chen, L. Sun, H. et al. Chinese Journal of Sports Medicine (中国运动医学杂志), 34 (8): 775–780 (2015).
 BEDFORD TG, TIPTON CM, WILSON NC, et al. Maximum oxygen consumption of rats and its changes with various experimental procedures. J Appl Physiol, 1979, 47 (6): 1278–1283.
 Zhen, J. & Li, X. Chinese Journal of Rehabilitation Medicine (中国康复医学杂志), 30 (12): 1212–1216 (2015).
 Shi, M. & Li, X. Journal of Physical Education (体育学刊), 22 (3): 127–134 (2015).
 Zhen, J. & Li, X. Chinese Journal of Pathophysiology (中国病理生理杂志), 31 (6): 973–979 (2015).
 Cheng, L. & Li, X. Journal of Shandong Institute of Physical Education and Sports (山东体育学院学报), 31 (1): 80–84 (2015).
 HIRAI DM, COPP SW, FERGUSON SK, et al. Neuronal nitric oxide synthase regulation of skeletal muscle functional hyperemia: exercise training and moderate compensated heart failure. Nitric Oxide, 2018, 74: 1–9.
 JAENISCH RB, STEFANI GP, DURANTE C, et al. Respiratory muscle training decreases diaphragm DNA damage in rats with heart failure. Can J Physiol Pharmacol, 2018, 96 (3): 221–226.
 OMAR W, PANDEY A, HAYKOWSKY MJ, et al. The evolving role of cardiorespiratory fitness and exercise in prevention and management of heart failure. Curr Heart Fail Rep, 2018, 15 (2): 75–80.
 ZHANG Y, XU L, YAO Y, et al. Effect of short-term exercise intervention on cardiovascular functions and quality of life of chronic heart failure patients: a meta-analysis. J Exerc Sci Fit, 2016, 14 (2): 67–75.
 GAUDRON P, HU K, SCHAMBERGER R, et al. Effect of endurance training early or late after coronary artery occlusion on left ventricular remodeling, hemodynamics, and survival in rats with chronic transmural myocardial infarction. Circulation, 1994, 89 (1): 402–412.
 AGARWAL AK, VENUGOPALAN P, WOODHOUSE C, et al. Catecholamine levels in heart failure due to dilated cardiomyopathy and their relationship to the severity of heart failure. Eur J Heart Fail, 2000, 2 (3): 261–263.
 STARKE K. History of catecholamine research. Chem Immunol Allergy, 2014, 100: 288–301.
 VARGHESE RT, JOHN AM, PAUL TV. Catecholamine induced cardiomyopathy in pheochromocytoma. Indian J Endocrinol Metab, 2013, 17 (4): 733–735.
 RENGO G, GALASSO G, FEMMINELLA GD, et al. Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure. Eur J Prev Cardiol, 2014, 21 (1): 4–11.
 SALAZAR NC, VALLEJOS X, SIRYK A, et al. GRK2blockade with βARKct is essential for cardiac β2-adrenergic receptor signaling towards increased contractility. Cell Commun Signal, 2013, 11: 64–68.
 DOGGRELL SA. Moxonidine: some controversy. Expert Opin Pharmacother, 2001, 2 (2): 337–350.
 EDWARDS LP, BROWN-BRYAN TA, MCLEAN L, et al. Pharmacological properties of the central antihypertensive agent, moxonidine. Cardiovasc Ther, 2012, 30 (4): 199–208.
 PALKOVITS M, EBEKOVK, KLENOVICS KS, et al. Neuronal activation in the central nervous system of rats in the initial stage of chronic kidney disease-modulatory effect of losartan and moxonidine. PLo S One, 2013, 8 (6): e66543.