Cardiovascular Toxicology

, Volume 16, Issue 3, pp 276–285 | Cite as

Paraventricular Nucleus Infusion of Epigallocatechin-3-O-Gallate Improves Renovascular Hypertension

  • Qiu-Yue Yi
  • Jie Qi
  • Xiao-Jing Yu
  • Hong-Bao Li
  • Yan Zhang
  • Qing Su
  • Tao Shi
  • Dong-Mei Zhang
  • Jing Guo
  • Zhi-Peng Feng
  • Mo-Lin Wang
  • Guo-Qing Zhu
  • Jin-Jun Liu
  • Xiao-Lian Shi
  • Yu-Ming Kang
Article

Abstract

Oxidative stress plays an important role in the pathogenesis of hypertension. Epigallocatechin-3-O-gallate (EGCG) is the main polyphenol present in green tea and is known for its potent antioxidant and anti-inflammatory properties. In the present study, we hypothesize that EGCG attenuates oxidative stress in the paraventricular nucleus of hypothalamus (PVN), thereby decreasing the blood pressure and sympathetic activity in renovascular hypertensive rats. After renovascular hypertension was induced in male Sprague-Dawley rats by the two-kidney one-clip (2K-1C) method, the rats received bilateral PVN infusion of EGCG (20 μg/h) or vehicle via osmotic minipump for 4 weeks. Our results were shown as follows: (1) Hypertension induced by 2K-1C was associated with the production of reactive oxygen species in the PVN; (2) chronic infusion of EGCG in the PVN decreased stress-related NAD(P)H oxidase subunit gp91phox and NOX-4 and increased the activity of antioxidant enzymes (SOD-1), also balanced the content of cytokines (IL-1β, IL-6, IL-10 and MCP-1) in the PVN, and attenuated the level of norepinephrine in plasma of 2K-1C rats. Our findings provide strong evidence that PVN infusion of EGCG inhibited renovascular hypertension progression through its potent anti-oxidative and anti-inflammatory activity in the PVN.

Keywords

Epigallocatechin-3-O-gallate Hypothalamic paraventricular nucleus Hypertension Oxidative stress Cytokines 

Notes

Acknowledgments

This study was supported by National Basic Research Program of China (No. 2012CB517805) and National Natural Science Foundation of China (Nos. 91439120, 81471471, 81170248, 81370356, 31171095). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with Ethical Standards

Conflict of interest

None of the listed authors has any financial or other interests that could be of conflict.

References

  1. 1.
    Alderman, M. H., & Ogihara, T. (2007). Global challenge for overcoming high blood pressure: Fukuoka Statement, 19 October 2006. Journal of Hypertension, 25, 727.CrossRefPubMedGoogle Scholar
  2. 2.
    Lopez, A. D., Mathers, C. D., Ezzati, M., Jamison, D. T., & Murray, C. J. (2006). Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data. Lancet, 367, 1747–1757.CrossRefPubMedGoogle Scholar
  3. 3.
    Kearney, P. M., Whelton, M., Reynolds, K., Muntner, P., Whelton, P. K., & He, J. (2005). Global burden of hypertension: Analysis of worldwide data. Lancet, 365, 217–223.CrossRefPubMedGoogle Scholar
  4. 4.
    Behradmanesh, S., & Nasri, H. (2013). Association of serum calcium with level of blood pressure in type 2 diabetic patients. Journal of Nephropathology, 2, 254–257.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Lenfant, C., Chobanian, A. V., Jones, D. W., & Roccella, E. J. (2003). Seventh report of the Joint National Committee on the prevention, detection, evaluation, and treatment of high blood pressure (JNC 7): Resetting the hypertension sails. Hypertension, 41, 1178–1179.CrossRefPubMedGoogle Scholar
  6. 6.
    Mittal, B. V., & Singh, A. K. (2010). Hypertension in the developing world: Challenges and opportunities. American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation, 55, 590–598.CrossRefGoogle Scholar
  7. 7.
    Savoia, C., Burger, D., Nishigaki, N., Montezano, A., & Touyz, R. M. (2011). Angiotensin II and the vascular phenotype in hypertension. Expert Reviews in Molecular Medicine, 13, e11.CrossRefPubMedGoogle Scholar
  8. 8.
    Belmonte, S. L., & Blaxall, B. C. (2011). G protein coupled receptor kinases as therapeutic targets in cardiovascular disease. Circulation Research, 109, 309–319.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Zubcevic, J., Waki, H., Raizada, M. K., & Paton, J. F. (2011). Autonomic-immune-vascular interaction: an emerging concept for neurogenic hypertension. Hypertension, 57, 1026–1033.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Muller, D. N., Kvakan, H., & Luft, F. C. (2011). Immune-related effects in hypertension and target-organ damage. Current Opinion in Nephrology and Hypertension, 20, 113–117.CrossRefPubMedGoogle Scholar
  11. 11.
    Touyz, R. M. (2005). Molecular and cellular mechanisms in vascular injury in hypertension: Role of angiotensin II. Current Opinion in Nephrology and Hypertension, 14, 125–131.CrossRefPubMedGoogle Scholar
  12. 12.
    Baylis, C. (2012). Nitric oxide synthase derangements and hypertension in kidney disease. Current Opinion in Nephrology and Hypertension, 21, 1–6.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Rodrigo, R., Gonzalez, J., & Paoletto, F. (2011). The role of oxidative stress in the pathophysiology of hypertension. Hypertension Research: Official Journal of the Japanese Society of Hypertension, 34, 431–440.CrossRefGoogle Scholar
  14. 14.
    Wilcox, C. S. (2005). Oxidative stress and nitric oxide deficiency in the kidney: A critical link to hypertension? American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 289, R913–R935.CrossRefPubMedGoogle Scholar
  15. 15.
    Vaziri, N. D. (2004). Roles of oxidative stress and antioxidant therapy in chronic kidney disease and hypertension. Current Opinion in Nephrology and Hypertension, 13, 93–99.CrossRefPubMedGoogle Scholar
  16. 16.
    Touyz, R. M. (2004). Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: What is the clinical significance? Hypertension, 44, 248–252.CrossRefPubMedGoogle Scholar
  17. 17.
    Droge, W. (2002). Free radicals in the physiological control of cell function. Physiological Reviews, 82, 47–95.CrossRefPubMedGoogle Scholar
  18. 18.
    Kakihana, T., Nagata, K., & Sitia, R. (2012). Peroxides and peroxidases in the endoplasmic reticulum: Integrating redox homeostasis and oxidative folding. Antioxidants and Redox Signaling, 16, 763–771.CrossRefPubMedGoogle Scholar
  19. 19.
    Laurindo, F. R., Pescatore, L. A., & Fernandes Dde, C. (2012). Protein disulfide isomerase in redox cell signaling and homeostasis. Free Radical Biology and Medicine, 52, 1954–1969.CrossRefPubMedGoogle Scholar
  20. 20.
    Lee, J., Giordano, S., & Zhang, J. (2012). Autophagy, mitochondria and oxidative stress: Cross-talk and redox signalling. The Biochemical Journal, 441, 523–540.CrossRefPubMedGoogle Scholar
  21. 21.
    Touyz, R. M., Briones, A. M., Sedeek, M., Burger, D., & Montezano, A. C. (2011). NOX isoforms and reactive oxygen species in vascular health. Molecular Interventions, 11, 27–35.CrossRefPubMedGoogle Scholar
  22. 22.
    Vaziri, N. D., & Rodriguez-Iturbe, B. (2006). Mechanisms of disease: Oxidative stress and inflammation in the pathogenesis of hypertension. Nature Clinical Practice Nephrology, 2, 582–593.CrossRefPubMedGoogle Scholar
  23. 23.
    Touyz, R. M., & Schiffrin, E. L. (2004). Reactive oxygen species in vascular biology: Implications in hypertension. Histochemistry and Cell Biology, 122, 339–352.CrossRefPubMedGoogle Scholar
  24. 24.
    Touyz, R. M., & Briones, A. M. (2011). Reactive oxygen species and vascular biology: Implications in human hypertension. Hypertension Research: Official Journal of the Japanese Society of Hypertension, 34, 5–14.CrossRefGoogle Scholar
  25. 25.
    Chen, D. D., Dong, Y. G., Yuan, H., & Chen, A. F. (2012). Endothelin 1 activation of endothelin A receptor/NADPH oxidase pathway and diminished antioxidants critically contribute to endothelial progenitor cell reduction and dysfunction in salt-sensitive hypertension. Hypertension, 59, 1037–1043.CrossRefPubMedGoogle Scholar
  26. 26.
    Huang, B. S., Zheng, H., Tan, J., Patel, K. P., & Leenen, F. H. (2011). Regulation of hypothalamic renin–angiotensin system and oxidative stress by aldosterone. Experimental Physiology, 96, 1028–1038.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Schupp, N., Kolkhof, P., Queisser, N., Gartner, S., Schmid, U., Kretschmer, A., et al. (2011). Mineralocorticoid receptor-mediated DNA damage in kidneys of DOCA-salt hypertensive rats. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 25, 968–978.CrossRefGoogle Scholar
  28. 28.
    Kimura, M., Umegaki, K., Kasuya, Y., Sugisawa, A., & Higuchi, M. (2002). The relation between single/double or repeated tea catechin ingestions and plasma antioxidant activity in humans. European Journal of Clinical Nutrition, 56, 1186–1193.CrossRefPubMedGoogle Scholar
  29. 29.
    Frei, B., & Higdon, J. V. (2003). Antioxidant activity of tea polyphenols in vivo: Evidence from animal studies. The Journal of Nutrition, 133, 3275S–3284S.PubMedGoogle Scholar
  30. 30.
    Higdon, J. V., & Frei, B. (2003). Tea catechins and polyphenols: Health effects, metabolism, and antioxidant functions. Critical Reviews in Food Science and Nutrition, 43, 89–143.CrossRefPubMedGoogle Scholar
  31. 31.
    Thomas, R., & Kim, M. H. (2005). Epigallocatechin gallate inhibits HIF-1α degradation in prostate cancer cells. Biochemical and Biophysical Research Communications, 334, 543–548.CrossRefPubMedGoogle Scholar
  32. 32.
    Zaveri, N. T. (2006). Green tea and its polyphenolic catechins: Medicinal uses in cancer and noncancer applications. Life Sciences, 78, 2073–2080.CrossRefPubMedGoogle Scholar
  33. 33.
    Nakachi, K., Matsuyama, S., Miyake, S., Suganuma, M., & Imai, K. (2000). Preventive effects of drinking green tea on cancer and cardiovascular disease: Epidemiological evidence for multiple targeting prevention. BioFactors, 13, 49–54.CrossRefPubMedGoogle Scholar
  34. 34.
    Kang, W. S., Lim, I. H., Yuk, D. Y., Chung, K. H., Park, J. B., Yoo, H. S., et al. (1999). Antithrombotic activities of green tea catechins and (–)-epigallocatechin gallate. Thrombosis Research, 96, 229–237.CrossRefPubMedGoogle Scholar
  35. 35.
    Townsend, P. A., Scarabelli, T. M., Pasini, E., Gitti, G., Menegazzi, M., Suzuki, H., et al. (2004). Epigallocatechin-3-gallate inhibits STAT-1 activation and protects cardiac myocytes from ischemia/reperfusion-induced apoptosis. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 18, 1621–1623.Google Scholar
  36. 36.
    Lorenz, M., Wessler, S., Follmann, E., Michaelis, W., Dusterhoft, T., Baumann, G., et al. (2004). A constituent of green tea, epigallocatechin-3-gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation. The Journal of Biological Chemistry, 279, 6190–6195.CrossRefPubMedGoogle Scholar
  37. 37.
    Baluchnejadmojarad, T., & Roghani, M. (2011). Chronic epigallocatechin-3-gallate ameliorates learning and memory deficits in diabetic rats via modulation of nitric oxide and oxidative stress. Behavioural Brain Research, 224, 305–310.CrossRefPubMedGoogle Scholar
  38. 38.
    Baba, Y., Sonoda, J. I., Hayashi, S., Tosuji, N., Sonoda, S., Makisumi, K., et al. (2012). Reduction of oxidative stress in liver cancer patients by oral green tea polyphenol tablets during hepatic arterial infusion chemotherapy. Experimental and Therapeutic Medicine, 4, 452–458.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Kochi, T., Shimizu, M., Terakura, D., Baba, A., Ohno, T., Kubota, M., et al. (2014). Non-alcoholic steatohepatitis and preneoplastic lesions develop in the liver of obese and hypertensive rats: Suppressing effects of EGCG on the development of liver lesions. Cancer Letters, 342, 60–69.CrossRefPubMedGoogle Scholar
  40. 40.
    Wang, M. H., Chang, W. J., Soung, H. S., & Chang, K. C. (2012). (–)-Epigallocatechin-3-gallate decreases the impairment in learning and memory in spontaneous hypertension rats. Behavioural Pharmacology, 23, 771–780.CrossRefPubMedGoogle Scholar
  41. 41.
    Hodgson, J. M., & Croft, K. D. (2010). Tea flavonoids and cardiovascular health. Molecular Aspects of Medicine, 31, 495–502.CrossRefPubMedGoogle Scholar
  42. 42.
    Babu, P. V., & Liu, D. (2008). Green tea catechins and cardiovascular health: An update. Current Medicinal Chemistry, 15, 1840–1850.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Potenza, M. A., Marasciulo, F. L., Tarquinio, M., Tiravanti, E., Colantuono, G., Federici, A., et al. (2007). EGCG, a green tea polyphenol, improves endothelial function and insulin sensitivity, reduces blood pressure, and protects against myocardial I/R injury in SHR. American Journal of Physiology. Endocrinology and metabolism, 292, E1378–E1387.CrossRefPubMedGoogle Scholar
  44. 44.
    Su, Q., Qin, D. N., Wang, F. X., Ren, J., Li, H. B., Zhang, M., et al. (2014). Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system and proinflammatory cytokines in hypertension. Toxicology and Applied Pharmacology, 276, 115–120.CrossRefPubMedGoogle Scholar
  45. 45.
    Kang, Y. M., Ma, Y., Zheng, J. P., Elks, C., Sriramula, S., Yang, Z. M., et al. (2009). Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension. Cardiovascular Research, 82, 503–512.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Cardinale, J. P., Sriramula, S., Mariappan, N., Agarwal, D., & Francis, J. (2012). Angiotensin II-induced hypertension is modulated by nuclear factor-kappa B in the paraventricular nucleus. Hypertension, 59, 113–121.CrossRefPubMedGoogle Scholar
  47. 47.
    Zimmerman, M. C., Lazartigues, E., Sharma, R. V., & Davisson, R. L. (2004). Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system. Circulation Research, 95, 210–216.CrossRefPubMedGoogle Scholar
  48. 48.
    Kang, Y. M., Chen, J. Y., Ouyang, W., Qiao, J. T., Reyes-Vazquez, C., & Dafny, N. (2004). Serotonin modulates hypothalamic neuronal activity. The International Journal of Neuroscience, 114, 299–319.CrossRefPubMedGoogle Scholar
  49. 49.
    Han, Y., Fan, Z. D., Yuan, N., Xie, G. Q., Gao, J., De, W., et al. (2011). Superoxide anions in the paraventricular nucleus mediate the enhanced cardiac sympathetic afferent reflex and sympathetic activity in renovascular hypertensive rats. Journal of Applied Physiology, 110, 646–652.CrossRefPubMedGoogle Scholar
  50. 50.
    Zhu, G. Q., Xu, Y., Zhou, L. M., Li, Y. H., Fan, L. M., Wang, W., et al. (2009). Enhanced cardiac sympathetic afferent reflex involved in sympathetic overactivity in renovascular hypertensive rats. Experimental Physiology, 94, 785–794.CrossRefPubMedGoogle Scholar
  51. 51.
    Kang, Y. M., He, R. L., Yang, L. M., Qin, D. N., Guggilam, A., Elks, C., et al. (2009). Brain tumour necrosis factor-alpha modulates neurotransmitters in hypothalamic paraventricular nucleus in heart failure. Cardiovascular Research, 83, 737–746.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Qi, J., Zhang, D. M., Suo, Y. P., Song, X. A., Yu, X. J., Elks, C., et al. (2013). Renin–angiotensin system modulates neurotransmitters in the paraventricular nucleus and contributes to angiotensin II-induced hypertensive response. Cardiovascular Toxicology, 13, 48–54.CrossRefPubMedGoogle Scholar
  53. 53.
    Li, H. B., Qin, D. N., Ma, L., Miao, Y. W., Zhang, D. M., Lu, Y., et al. (2014). Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension. Toxicology and Applied Pharmacology, 279, 141–149.CrossRefPubMedGoogle Scholar
  54. 54.
    Gao, L., Wang, W., Li, Y. L., Schultz, H. D., Liu, D., Cornish, K. G., et al. (2005). Sympathoexcitation by central ANG II: Roles for AT1 receptor upregulation and NAD(P)H oxidase in RVLM. American Journal of Physiology. Heart and circulatory Physiology, 288, H2271–H2279.CrossRefPubMedGoogle Scholar
  55. 55.
    Kang, Y. M., Zhang, Z. H., Johnson, R. F., Yu, Y., Beltz, T., Johnson, A. K., et al. (2006). Novel effect of mineralocorticoid receptor antagonism to reduce proinflammatory cytokines and hypothalamic activation in rats with ischemia-induced heart failure. Circulation Research, 99, 758–766.CrossRefPubMedGoogle Scholar
  56. 56.
    Agarwal, D., Welsch, M. A., Keller, J. N., & Francis, J. (2011). Chronic exercise modulates RAS components and improves balance between pro- and anti-inflammatory cytokines in the brain of SHR. Basic Research in Cardiology, 106, 1069–1085.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Coote, J. H. (2007). Landmarks in understanding the central nervous control of the cardiovascular system. Experimental Physiology, 92, 3–18.CrossRefPubMedGoogle Scholar
  58. 58.
    Joyner, M. J., Charkoudian, N., & Wallin, B. G. (2008). A sympathetic view of the sympathetic nervous system and human blood pressure regulation. Experimental Physiology, 93, 715–724.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Martinez-Maldonado, M. (1991). Pathophysiology of renovascular hypertension. Hypertension, 17, 707–719.CrossRefPubMedGoogle Scholar
  60. 60.
    Katholi, R. E., Whitlow, P. L., Winternitz, S. R., & Oparil, S. (1982). Importance of the renal nerves in established two-kidney, one clip Goldblatt hypertension. Hypertension, 4, 166–174.PubMedGoogle Scholar
  61. 61.
    Cohn, H. I., Harris, D. M., Pesant, S., Pfeiffer, M., Zhou, R. H., Koch, W. J., et al. (2008). Inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances α1D-adrenergic receptor constriction. American Journal of Physiology. Heart and circulatory physiology, 295, H1695–H1704.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Campos, R. R., Oliveira-Sales, E. B., Nishi, E. E., Boim, M. A., Dolnikoff, M. S., & Bergamaschi, C. T. (2011). The role of oxidative stress in renovascular hypertension. Clinical and Experimental Pharmacology and Physiology, 38, 144–152.CrossRefPubMedGoogle Scholar
  63. 63.
    Chen, A. D., Zhang, S. J., Yuan, N., Xu, Y., De, W., Gao, X. Y., et al. (2011). Angiotensin AT1 receptors in paraventricular nucleus contribute to sympathetic activation and enhanced cardiac sympathetic afferent reflex in renovascular hypertensive rats. Experimental Physiology, 96, 94–103.CrossRefPubMedGoogle Scholar
  64. 64.
    Maliszewska-Scislo, M., Chen, H., Augustyniak, R. A., Seth, D., & Rossi, N. F. (2008). Subfornical organ differentially modulates baroreflex function in normotensive and two-kidney, one-clip hypertensive rats. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 295, R741–R750.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Kishi, T., & Hirooka, Y. (2012). Oxidative stress in the brain causes hypertension via sympathoexcitation. Frontiers in Physiology, 3, 335.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Wu, K. L., Chan, S. H., & Chan, J. Y. (2012). Neuroinflammation and oxidative stress in rostral ventrolateral medulla contribute to neurogenic hypertension induced by systemic inflammation. Journal of Neuroinflammation, 9, 212.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Zimmerman, M. C., Sharma, R. V., & Davisson, R. L. (2005). Superoxide mediates angiotensin II-induced influx of extracellular calcium in neural cells. Hypertension, 45, 717–723.CrossRefPubMedGoogle Scholar
  68. 68.
    Shi, Z., Gan, X. B., Fan, Z. D., Zhang, F., Zhou, Y. B., Gao, X. Y., et al. (2011). Inflammatory cytokines in paraventricular nucleus modulate sympathetic activity and cardiac sympathetic afferent reflex in rats. Acta Physiologica (Oxf), 203, 289–297.CrossRefGoogle Scholar
  69. 69.
    Taubert, D., Roesen, R., & Schomig, E. (2007). Effect of cocoa and tea intake on blood pressure: A meta-analysis. Archives of Internal Medicine, 167, 626–634.CrossRefPubMedGoogle Scholar
  70. 70.
    Liu, P. L., Liu, J. T., Kuo, H. F., Chong, I. W., & Hsieh, C. C. (2014). Epigallocatechin gallate attenuates proliferation and oxidative stress in human vascular smooth muscle cells induced by interleukin-1beta via heme oxygenase-1. Mediators of Inflammation, 2014, 523684.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Steffen, Y., Gruber, C., Schewe, T., & Sies, H. (2008). Mono-O-methylated flavanols and other flavonoids as inhibitors of endothelial NADPH oxidase. Archives of Biochemistry and Biophysics, 469, 209–219.CrossRefPubMedGoogle Scholar
  72. 72.
    Rodrigo, R. (2012). Prevention of postoperative atrial fibrillation: Novel and safe strategy based on the modulation of the antioxidant system. Frontiers in Physiology, 3, 93.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Simic, D. V., Mimic-Oka, J., Pljesa-Ercegovac, M., Savic-Radojevic, A., Opacic, M., Matic, D., et al. (2006). Byproducts of oxidative protein damage and antioxidant enzyme activities in plasma of patients with different degrees of essential hypertension. Journal of Human Hypertension, 20, 149–155.CrossRefPubMedGoogle Scholar
  74. 74.
    Roghani, M., & Baluchnejadmojarad, T. (2009). Chronic epigallocatechin-gallate improves aortic reactivity of diabetic rats: underlying mechanisms. Vascular Pharmacology, 51, 84–89.CrossRefPubMedGoogle Scholar
  75. 75.
    Antonello, M., Montemurro, D., Bolognesi, M., Di Pascoli, M., Piva, A., Grego, F., et al. (2007). Prevention of hypertension, cardiovascular damage and endothelial dysfunction with green tea extracts. American Journal of Hypertension, 20, 1321–1328.CrossRefPubMedGoogle Scholar
  76. 76.
    Khalaf, A. A., Moselhy, W. A., & Abdel-Hamed, M. I. (2012). The protective effect of green tea extract on lead induced oxidative and DNA damage on rat brain. Neurotoxicology, 33, 280–289.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Qiu-Yue Yi
    • 1
    • 3
  • Jie Qi
    • 1
  • Xiao-Jing Yu
    • 1
  • Hong-Bao Li
    • 1
  • Yan Zhang
    • 1
  • Qing Su
    • 1
  • Tao Shi
    • 3
  • Dong-Mei Zhang
    • 4
  • Jing Guo
    • 1
  • Zhi-Peng Feng
    • 1
  • Mo-Lin Wang
    • 1
  • Guo-Qing Zhu
    • 5
  • Jin-Jun Liu
    • 1
  • Xiao-Lian Shi
    • 1
    • 2
  • Yu-Ming Kang
    • 1
  1. 1.Department of Physiology and Pathophysiology, School of Basic Medical SciencesXi’an Jiaotong University Health Science CenterXi’anChina
  2. 2.Department of Pharmacology, School of Basic Medical SciencesXi’an Jiaotong University Health Science CenterXi’anChina
  3. 3.Department of Cardiovascular SurgeryFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  4. 4.Department of PhysiologyDalian Medical UniversityDalianChina
  5. 5.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of PhysiologyNanjing Medical UniversityNanjingChina

Personalised recommendations