JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2016, Vol. 54 ›› Issue (2): 11-15.doi: 10.6040/j.issn.1671-7554.0.2015.513

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Chronic intermittent hypobaric hypoxia enhances the vasodilatation of thoracic aorta via PI3K-dependent eNOS activation in rats

WANG Lixuan1*, ZHANG Lu2*, XU Xin2, LI Sixue2, LIU Min3, WANG Yaping3, MA Huijuan3,4   

  1. 1. Department of Histology and Embryology;
    2. Class of Seven-year Clinical Medicine Registered in 2011;
    3. Department of Physiology;
    4. Hebei Key Laboratory of Laboratory Animal Science, Hebei Medical University, Shijiazhuang 050017, Hebei, China
  • Received:2015-05-24 Online:2016-02-10 Published:2016-02-10

Abstract: Objective To investigate the effects of chronic intermittent hypobaric hypoxia(CIHH)on the vasodilatation in isolated thoracic aorta and the nitric oxide related mechanism in rats. Methods A total of 80 male adult Sprague-Dawley rats were randomly divided into two groups: control group(CN, n=40)and CIHH group(CIHH, n=40). The rats in CIHH group were exposed to hypoxia simulating at 5000-meter altitude in a hypobaric chamber(PB=404 mmHg, PO2=84 mmHg)for 28 days, 6 hours each day. The rats in CN group lived in a normoxic environment for the same period. The vasodilatation of thoracic aorta was recorded by using organ bath technique. The protein expressions of eNOS and PI3K were measured by using Western blotting. Results CIHH could remarkably augment the acetylcholine(ACh)-induced vasodilatation of thoracic aorta(P<0.05)and increase the expression of eNOS in thoracic aorta tissues(P<0.05). Incubation with MEK inhibitor PD98059 did not affect the effects of CIHH on thoracic aorta. Incubation of PI3K inhibitor LY294002 blocked the effects of CIHH(P<0.05). Furthermore, CIHH treatment could improve the expression of PI3K in thoracic aorta tissue(P<0.05). Conclusion CIHH treatment enhances Ach-induced vasodilatation of thoracic aorta by activating eNOS via PI3K pathway.

Key words: PI3K, Anti-hypertension, Vasodilatation, Chronic intermittent hypobaric hypoxia, eNOS

CLC Number: 

  • Q463
[1] 张翼, 杨黄恬, 周兆年. 间歇性低氧适应的心脏保护[J]. 生理学报, 2007, 59(5):601-613. ZHANG Yi, YANG Huangtian, ZHOU Zhaonian. The cardioprotection of intermittent hypoxic adaptation[J]. Acta Physiologica Sinica, 2007, 59(5):601-613.
[2] Roels B, Bentley DJ, Coste O, et al. Effects of intermittent hypoxic training on cycling performance in well-trained athletes[J]. Eur J Appl Physiol, 2007, 10(3):359-368.
[3] Serebrovskaya TV, Nosar VI, Bratus LV, et al. Tissue oxygenation and mitochondrial respiration under different modes of intermittent hypoxia [J]. High Alt Med Biol, 2013, 14(3):280-288.
[4] Katiukhin VN, Ochirova A. Change of sensitivity to hypotensive treatment under the effect of intermittent altitude hypoxia[J]. Vrach Delo, 1979, 1(1):32-35.
[5] Xu P, Cao XB, Gao L, et al. Inhibition of carotid sinus baroreflex in neonatal rats exposed to chronic intermittent hypobaric hypoxia[J]. Chin J Physiol, 2014, 57(6):343-349.
[6] Tepavcevic S, Milutinovic DV, Macut D, et al. Cardiac nitric oxide synthases and Na+/K+-aTPase in the rat model of polycystic ovary syndrome induced by dihydrotestosterone[J]. Exp Clin Endocrinol Diabetes, 2015, 123(5):303-307.
[7] Liu H, Wang L, Ma H, et al. Coumestrol inhibits carotid sinus baroreceptor activity by cAMP/PKA dependent nitric oxide release in anesthetized male rats [J]. Biochem Pharmacol, 2015, 93(1):42-48.
[8] Nagai H, Kuwahira I, Schwenke DO, et al. Beta2-Adrenergic receptor-dependent attenuation of hypoxic pulmonary vasoconstriction prevents progression of pulmonary arterial hypertension in intermittent hypoxic rats[J]. PLoS One, 2014, 9(10):110693. doi:10.1371/journal.pone.011693.
[9] Shafiei M, Mahmoudian M. Atypical beta-adrenoceptors of rat thoracic aorta[J]. Gen Pharmacol, 1999, 32(5):557-562.
[10] Chen H, Shi B, Feng X, et al. Leptin and NAP2 promote mesenchymal stem cell senescence through activation of PI3K/Akt pathway in patients with systemic lupus erythematosus[J]. Arthritis Rheumatol, 2015, 67(9):2383-2393.
[11] Ning WH, Zhao K. Propionyl-L-carnitine induces eNOS activation and nitric oxide synthesis in endothelial cells via PI3 and Akt kinases[J]. Vascul Pharmacol, 2013, 59(3-4):76-82.
[12] Zhang Y, Zhou ZN. Beneficial effects of intermittent hypobaric hypoxia on the body[J]. Chinese Journal of Applied Physiology, 2012, 28(6):504-509.
[13] Zhen JL, Wang WP, Zhou JJ, et al. Chronic intermittent hypoxic preconditioning suppresses pilocarpine-induced seizures and associated hippocampal neurodegeneration[J]. Brain Res, 2014, 1563:122-130. doi:10.1016/j.brainres.2014.03.032.
[14] Yuan F, Teng X, Guo Z, et al. Chronic intermittent hypobaric hypoxia ameliorates endoplasmic reticulum stress mediated liver damage induced by fructose in rats[J]. Life Sci, 2015, 121:40-45. doi:10.1016/j.lfs.2014.11.019.
[15] Li XF, Wan TT, Sun YM, et al. Na+/Ca2+ exchanger inhibitor restores endothelium-dependent relaxation in diabetic rat aorta[J]. Exp Clin Endocrinol Diabetes, 2015, 123(7):394-397.
[16] 姜秀峰, 苏梅, 丁文筱, 等. 慢性间歇低氧对大鼠心血管系统的影响及脂联素的保护作用[J]. 中华结核和呼吸杂志, 2014, 37(12):888-892. JIANG Xiufeng, SU Mei, DING Wenxiao, et al. A study on rat cardiovascular injury induced by intermittent hypoxia and the protective role of adiponectin[J]. Chinese Journal of Tuberculosis and Respiratory Diseases, 2014, 37(12):888-892.
[17] 张凤伟, 吴树明, 曹广庆, 等. eNOS基因转染治疗兔肺动脉高压及肺动脉高压危象[J]. 山东大学学报(医学版), 2010, 49(9):19-24. ZHANG Fengwei, WU Shuming, CAO Guangqing, et al. eNOS gene transfection on pulmonary artery hypertension and hypertension crisis in rabbits[J]. Journal of Shandong University(Health Sciences), 2010, 49(9):19-24.
[18] 冯晓丽, 朱晓波, 陈欧, 等. 腺病毒介导eNOS转染高肺血流肺动脉高压大鼠模型的研究[J]. 山东大学学报(医学版), 2010, 49(1):70-73. FENG Xiaoli, ZHU Xiaobo, CHEN Ou, et al. Effect of adenovirus-mediated human endothelial nitric oxide synthase gene transfection on pulmonary hypertension rat model induced by high pulmonary blood flow[J]. Journal of Shandong University(Health Sciences), 2010, 49(1):70-73.
[19] Reddy GR, Subramanian H, Birk A, et al. Adenylyl cyclases 5 and 6 underlie PIP3-dependent regulation[J]. FASEB J, 2015, 29(8):3458-3471.
[20] Kimmoun A, Louis H, Kattani NA, et al. β1-Adrenergic inhibition improves cardiac and vascular unction in experimental septic shock [J]. Crit Care Med, 2015, 43(9):332-340.
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