Abstract | OBJECTIVE: Physical activity has been shown to improve cardiovascular function and to be beneficial to type 2 diabetic patients. However, the effects of aerobic exercise (AE) on myocardial ischemia/reperfusion (MI/R) are largely unclear. Therefore, the aims of the present study were to determine whether long-term AE can protect the heart against I/R injury, and if so, to investigate the underlying mechanism. METHODS: Adult male Sprague-Dawley rats were randomly subjected to 8 weeks of either sedentary or free-loading swimming exercise (3 h/day, 5 d/week). Then the animals were subjected to 30 min MI followed by 4 h R. Arterial blood pressure and left ventricular pressure (LVP) were monitored throughout the whole MI/R procedure. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activities were measured spectrophotometrically. Myocardial infarction and myocardial apoptosis (TUNEL analysis) were determined in a blinded manner. RESULTS: MI/R caused significant cardiac dysfunction and myocardial apoptosis (strong TUNEL-positive staining). Compared with sedentary group, rats subjected to 8 weeks of AE showed protection against MI/R as evidenced by reduced myocardial infarction (26.8 +/- 1.5% vs. 35.3 +/- 2.4%, n = 8, P < 0.05), inhibited cardiomyocyte apoptosis (decreased apoptotic index (12.4 +/- 1.1% vs. 21.0 +/- 1.7%, n = 8, P < 0.01) and decreased myocardial caspase-3 activity), decreased plasma CK and LDH activities and improved recovery of cardiac systolic/diastolic function (including LVSP and +/-LVdP/dt) at the end of R. Moreover, exercise resulted in 1.7-fold, 2.5-fold and 2.5-fold increases in Akt expression, Akt phosphorylation and glycogen synthase kinase-3beta phosphorylation in I/R myocardium, respectively (n = 3, all P < 0.05). More importantly, treatment with wortmannin, a PI3 kinase inhibitor, 15 min before R not only significantly blocked Akt phosphorylation (P < 0.05) in exercise rats, but also abolished long-term AE-induced cardioprotection for the I/R heart as manifested by increased apoptosis and myocardial infarction, and reduced cardiac function. CONCLUSION: Long-term AE exerts cardioprotective effect against MI/R injury, including anti-cardiomyocyte apoptosis, which is at least partly via PI3 kinase-dependent and Akt-mediated mechanism.
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Authors | Kun-Ru Zhang, Hai-Tao Liu, Hai-Feng Zhang, Quan-Jiang Zhang, Qiu-Xia Li, Qiu-Jun Yu, Wen-Yi Guo, Hai-Chang Wang, Feng Gao |
Journal | Apoptosis : an international journal on programmed cell death
(Apoptosis)
Vol. 12
Issue 9
Pg. 1579-88
(Sep 2007)
ISSN: 1360-8185 [Print] Netherlands |
PMID | 17505785
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Androstadienes
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
- Creatine Kinase
- Casp3 protein, rat
- Caspase 3
- Hydro-Lyases
- lactate dehydratase
- Wortmannin
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Topics |
- Androstadienes
(pharmacology)
- Animals
- Apoptosis
(physiology)
- Caspase 3
(metabolism)
- Creatine Kinase
(blood)
- Heart
(physiology)
- Hydro-Lyases
(blood)
- In Situ Nick-End Labeling
- Male
- Myocardial Infarction
(pathology)
- Myocardial Reperfusion Injury
(prevention & control)
- Myocardium
(metabolism)
- Myocytes, Cardiac
(pathology)
- Phosphatidylinositol 3-Kinases
(physiology)
- Physical Conditioning, Animal
(physiology)
- Proto-Oncogene Proteins c-akt
(physiology)
- Rats
- Rats, Sprague-Dawley
- Swimming
- Wortmannin
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