Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license


1 Professor, PhD of Exercise Physiology, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Mazandaran, Babolsar, Iran

2 Assistant Professor, PhD of Comparative Histology, Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

3 . PhD of Exercise Physiology, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Mazandaran, Babolsar, Iran


VEGF-2 has most potent angiogenic signaling associated with VEGF that So far,no has been published research in relation to the effect of exercise training on the vascular volume and it, in the lung . therefore, present study aim was investigate the effect of an high-intensity interval training period on VEGFR-2 expression and pulmonary vascular volume in male Wistar rats. This research including the experimental studies that samples its had formed 10 male Wistar rats,that to form of Randomly and equally were divided into training and control groups. Training program Was started with 25 meters per minute and with 70 meters per minute was Finished at the end of the period. In each training session, rats completed the 1-min activity with 10 repetition and work to rest ratio was 1:2. In the end, lung tissue extracted for stereologicaly and Immunohistochemistry tests. Statistical analysis whit Independent t-test, and Pearson correlation coefficient showed, significantly increase in VEGFR-2(sig: 0/001) and pulmonary vascular volume(sig: 0/042) in the exercise group compared to the control group, and positive correlation between changes in these two indicators whit exercise(sig: 0/035). In general it seems that 6 weeks of high-intensity interval training has potential to promote of lung angiogenic processes.


1.    Jung ME, Bourne JE, Beauchamp MR, Robinson E, Little JP. High-intensity interval training as an efficacious alternative to moderate-intensity continuous training for adults with prediabetes. Journal of diabetes research. 2015;2015.
2.    Milanović Z, Sporiš G, Weston M. Effectiveness of high-intensity interval training (HIT) and continuous endurance training for VO 2max improvements: a systematic review and meta-analysis of controlled trials. Sports Medicine. 2015;45(10):1469-81.
3.    Yadegari M Mirdar S, Hamidian G. The effect of high-intensity interval training on lung parenchymal and non-parenchymal structural changes. Daneshvar Medicine Journal 2016;23(124):56-60.
4.    Little JP, Safdar A, Bishop D, Tarnopolsky MA, Gibala MJ. An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1α and activates mitochondrial biogenesis in human skeletal muscle. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2011;300(6):R1303-R10.
5.    Voelkel NF, Vandivier RW, Tuder RM. Vascular endothelial growth factor in the lung. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2006;290(2):L209-L21.
6.    Maeda S, Suzuki S, Suzuki T, Endo M, Moriya T, Chida M, et al. Analysis of intrapulmonary vessels and epithelial-endothelial interactions in the human developing lung. Laboratory investigation. 2002;82(3):293.
7.    Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocrine reviews. 2004;25(4):581-611.
8.    Keong CC, Singh HJ, Singh R. Effects of palm vitamin E supplementation on exercise-induced oxidative stress and endurance performance in the heat. Journal of sports science & medicine. 2006;5(4):629.
9.    Keglowich L, Borger P. The three A’s in asthma–airway smooth muscle, airway remodeling & angiogenesis. The open respiratory medicine journal. 2015;9:70.
10.    Kasahara Y, Tuder RM, Taraseviciene-Stewart L, Le Cras TD, Abman S, Hirth PK, et al. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. The Journal of clinical investigation. 2000;106(11):1311-9.
11.    Marini M, Falcieri E, Margonato V, Treré D, Lapalombella R, Di Tullio S, et al. Partial persistence of exercise-induced myocardial angiogenesis following 4-week detraining in the rat. Histochemistry and cell biology. 2008;129(4):479-87.
12.    Pryor JS, Montani J-P, Adair TH. Angiogenic growth factor responses to long-term treadmill exercise in mice. Indian journal of physiology and pharmacology. 2010;54(4):309.
13.    Hoier B, Passos M, Bangsbo J, Hellsten Y. Intense intermittent exercise provides weak stimulus for vascular endothelial growth factor secretion and capillary growth in skeletal muscle. Experimental physiology. 2013;98(2):585-97.
14.    Helgerud J, Høydal K, Wang E, Karlsen T, Berg P, Bjerkaas M, et al. Aerobic high-intensity intervals improve V˙ O2max more than moderate training. Medicine & Science in Sports & Exercise. 2007;39(4):665-71.
15.    Yadegari M Riahi S, Mirdar S, Hamidian G, Mosadegh zavaragh P. Effect of the Adiantum capillus Veneris Extract on Bax and Bcl2 Apoptotic Markers of Lung Modulation in Trained Rats and Exposed to Hypoxic Stress. Journal of Medicinal Plants. 2018;4(64):162-71.
16.    Yadegari M, Riahi S, Mirdar S, Hamidiyan GH,  yousefpour M. Riyahi F. Immunohistochemical detection of apoptotic factors Bax and Bcl-2 in the lung alveoli, followed by six weeks of high intensity exercise training. Daneshvar Medicine. 2016;24(129):31-40.
17.    Di Cataldo S, Ficarra E, Acquaviva A, Macii E. Automated segmentation of tissue images for computerized IHC analysis. Computer methods and programs in biomedicine. 2010;100(1):1-15.
18.    GILANI K, Vafakhah M. Hypoxia: a review. 2010.
19.    Heusner AA. Body size, energy metabolism, and the lungs. Journal of Applied Physiology. 1983;54(4):867-73.
20.    ROBB GP, Steinberg I. visolization of the chambers of the heart: the pulmonary circulation and the great blood vessels in man: sumaary of methods and results. Journal of the American Medical Association. 1940;114(6):474-80.
21.    Iemitsu M, Maeda S, Jesmin S, Otsuki T, Miyauchi T. Exercise training improves aging-induced downregulation of VEGF angiogenic signaling cascade in hearts. American Journal of Physiology-Heart and Circulatory Physiology. 2006;291(3):H1290-H8.
22.    Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, DiMenna FJ, Wilkerson DP, et al. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. Journal of Applied Physiology. 2009;107(4):1144-55.
23.    Nilsson I, Rolny C, Wu Y, Pytowski B, Hicklin D, Alitalo K, et al. Vascular endothelial growth factor receptor-3 in hypoxia-induced vascular development. The FASEB Journal. 2004;18(13):1507-15.
24.    Tuder RM, Flook BE, Voelkel NF. Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide. The Journal of clinical investigation. 1995;95(4):1798-807.
25.    Hudlicka O, Brown MD. Adaptation of skeletal muscle microvasculature to increased or decreased blood flow: role of shear stress, nitric oxide and vascular endothelial growth factor. Journal of vascular research. 2009;46(5):504-12.
26.    Egginton S. Invited review: activity-induced angiogenesis. Pflügers Archiv-European Journal of Physiology. 2009;457(5):963.
27.    Lee HJ, Koh GY. Shear stress activates Tie2 receptor tyrosine kinase in human endothelial cells. Biochemical and biophysical research communications. 2003;304(2):399-404.
28.    Chikara Goto R, Higashi Y, Kimura M, Noma K, Hara K, Nakagawa K, et al. Effect of Different Intensities of Exercise on Endothelium-Dependent Vasodilation in Humans. 2003.
29.    Zhao W, Zhao T, Chen Y, Ahokas RA, Sun Y. Reactive oxygen species promote angiogenesis in the infarcted rat heart. International journal of experimental pathology. 2009;90(6):621-9.
30.    Fisher-Wellman K, Bloomer RJ. Acute exercise and oxidative stress: a 30 year history. Dynamic medicine. 2009;8(1):1.
31.    Kim Y-W, Byzova TV. Oxidative stress in angiogenesis and vascular disease. Blood. 2014;123(5):625-31.
32.    Skurk C, Maatz H, Rocnik E, Bialik A, Force T, Walsh K. Glycogen-synthase kinase3β/β-catenin axis promotes angiogenesis through activation of vascular endothelial growth factor signaling in endothelial cells. Circulation research. 2005;96(3):308-18.
33.    Cardone MH, Roy N, Stennicke HR, Salvesen GS, Franke TF, Stanbridge E, et al. Regulation of cell death protease caspase-9 by phosphorylation. Science. 1998;282(5392):1318-21.
34.    Cross MJ, Dixelius J, Matsumoto T, Claesson-Welsh L. VEGF-receptor signal transduction. Trends in biochemical sciences. 2003;28(9):488-94.