title: Exercise protects against chronic β-adrenergic remodeling of the heart by activation of endothelial nitric oxide synthase.
abstract: Extensive data have shown that exercise training can provide cardio-protection against pathological cardiac hypertrophy. However, how long the heart can retain cardio-protective phenotype after the cessation of exercise is currently unknown. In this study, we investigated the time course of the loss of cardio-protection after cessation of exercise and the signaling molecules that are responsible for the possible sustained protection. Mice were made to run on a treadmill six times a week for 4 weeks and then rested for a period of 0, 1, 2 and 4 weeks followed by isoproterenol injection for 8 days. Morphological, echocardiographic and hemodynamic changes were measured, gene reactivation was determined by real-time PCR, and the expression and phosphorylation status of several cardio-protective signaling molecules were analyzed by Western-blot. HW/BW, HW/TL and LW/BW decreased significantly in exercise training (ER) mice. The less necrosis and lower fetal gene reactivation induced by isoproterenol injection were also found in ER mice. The echocardiographic and hemodynamic changes induced by β-adrenergic overload were also attenuated in ER mice. The protective effects can be sustained for at least 2 weeks after the cessation of the training. Western-blot analysis showed that the alterations in the phosphorylation status of endothelial nitric oxide synthase (eNOS) (increase in serine 1177 and decrease in threonine 495) continued for 2 weeks after the cessation of the training whereas increases of the phosphorylation of Akt and mTOR disappeared. Further study showed that L-NG-Nitroarginine methyl ester (L-NAME) treatment abolished the cardio-protective effects of ER. Our findings demonstrate that stimulation of eNOS in mice through exercise training provides acute and sustained cardioprotection against cardiac hypertrophy.
authors.affiliation: Department of Pharmacology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.affiliation: Departments of Histology and Embryology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Departments of Histology and Embryology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Departments of Histology and Embryology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Jincai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Departments of Histology and Embryology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Wencong
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of Pharmacology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Departments of Histology and Embryology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Department of Pharmacology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D005355:Fibrosis; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D011943:Receptors, Adrenergic, beta; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester