A novel strategy using radical scavengers against intermittent hypoxia-induced oxidative stress in heart, kidney, and brain

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590267
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Osaka Medical College
• Principal Investigator: HAYASHI TETSUYA 大阪医科大学, 医学部, 非常勤講師 (30257852)
• Project Period (FY): 2011 – 2013
• Keywords: 間歇的低酸素負荷 / 糖尿病マウス / 心筋症ハムスター / 酸化ストレス / 水素ガス / ラジカルスカベンジャー / 大脳辺縁系 / Fos

Research Abstract

Intermittent hypoxia (IH) relevant to sleep apnea is known to increase the risk of cardiovascular morbidity and mortality. This study showed that IH increased superoxide production, oxidative stress, and inflammatory cytokine expression in heart and kidney, accelerating histological degeneration due to hypoxic stress. Inhalation of hydrogen (H2) gas improved lipid metabolism and reduced oxidative stress. Furthermore, H2 gas improved the deteriorated systolic function in Bio14.6 cardiomyopathic hamster exposed to IH. On the other hand, treatment with celiprolol, a beta 1-selective adrenoreceptor blocker, suppressed blood pressure fluctuation during IH, restored eNOS expression, and attenuated cardiac remodeling caused by IH. Intriguingly, limbic Fos expression was significantly suppressed in obese diabetic mice exposed to IH, associated with sedative and/or depressive behavioral signs, which may related to the neuropsychological disturbances in diabetic patients with sleep apnea.

Research Products

• [Journal Article] Celiprolol reduces oxidative stress and attenuates left ventricular remodeling induced by hypoxic stress in mice (2013)
  • Author(s): Nishioka S, Yoshioka T, Nomura A, Kato R, Miyamura M, Okada Y, Ishizaka N, Matsumura Y, Hayashi T
  • Journal Title: Hypertens Res Volume: 36 Pages: 934-939
  • DOI: 10.1038/hr.2013.60
• [Journal Article] Preferential suppression of limbic Fos expression by intermittent hypoxia in obese diabetic mice (2013)
  • Author(s): Mukai T, Nagao Y, Nishioka S, Hayashi T, Shimizu S, Ono A, Sakagami Y, Watanabe S, Ueda Y, Hara M, Tokudome K, Kato R, Matsumura Y, Ohno Y
  • Journal Title: Neuroscience Res Volume: 77 Pages: 202-207
  • DOI: 10.1016/j.neures.2013.09.013
• [Journal Article] Inhalation of hydrogen gas attenuates left ventricular remodeling induced by intermittent hypoxia in mice (2011)
  • Author(s): Hayashi T, Yoshioka T, Hasegawa K, Miyamura M, Mori T, Ukimura A, Matsumura Y, Ishizaka N
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 301 Pages: 1062-1069
  • DOI: 10.1152/ajpheart.00150.2011
• [Presentation] O-Linked N-Acetyl Glucosamine (O-GlcNAc) Regulates Autophagy and Apoptosis in Cardiomyocytes : a Double-Edged Sword in Intermittent Hypoxia-Induced Cardiac Remodeling (2014)
  • Author(s): Hayashi T, Sasaki M, Watanabe A, Furukawa Y, Nakagawa T, Nomura A, Uehashi W, Kato R, Ijiri Y, Yamaguchi T, Izumi Y, Yoshiyama M, Asahi M
  • Organizer: 64th ACC Congress 2014
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20140329-31
• [Presentation] Intermittent hypoxia accelerates cardiac remodeling and systolic dysfunction in cardiomyopathic hamster (2014)
  • Author(s): Nomura A, Kato R, Ijiri Y, Sakamoto A, Yamaguchi T, Izumi Y, Yoshiyama M, Tanaka K, Hayashi T
  • Organizer: 第78回日本循環器学会総会
  • Place of Presentation: 東京
  • Year and Date: 20140321-23
• [Presentation] Azilsartan reduces oxidative stress and attenuates cardiac remodeling induced by hypoxia in rats (2013)
  • Author(s): Fujiwara Y, Nomura A, Kato R, Miyamura M, Ijiri Y, Ishizama N, Hayashi T
  • Organizer: 第17回日本心不全学会学術集会
  • Place of Presentation: 大宮
  • Year and Date: 20131128-30
• [Presentation] 間歇的低酸素負荷に伴う血圧変動と酸化ストレスに対するceliprololの有効性 (2013)
  • Author(s): 東森健志, 西岡慧, 野村篤生, 加藤隆児, 宮村昌利, 石坂信和, 松村靖夫, 林哲也
  • Organizer: 第36回日本高血圧学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20131024-26
• [Presentation] 間歇的低酸素曝露による左室リモデリングに対する新規ARB azilsartanの効果 (2013)
  • Author(s): 上橋和佳, 野村篤生, 加藤隆児, 宮村昌利, 井尻好雄, 石坂信和, 林哲也
  • Organizer: 第61回日本心臓病学会
  • Place of Presentation: 熊本
  • Year and Date: 20130920-22
• [Presentation] 間歇的低酸素負荷が不全心に及ぼす影響と水素ガスのラジカルスカベンジ効果 (2013)
  • Author(s): 供田菜々花, 野村篤生, 加藤隆児, 井尻好雄, 宮村昌利, 石坂信和, 阪本英二, 田中一彦, 林哲也
  • Organizer: 第61回日本心臓病学会
  • Place of Presentation: 熊本
  • Year and Date: 20130920-22
• [Presentation] Role of Vascular Endothelial Growth Factor in Cardiac Remodeling due to Hypoxic Stress (2013)
  • Author(s): Woo E, Nishioka S, NemotoS, Katsumata T, Hayashi T
  • Organizer: 23rd European Meeting on Hypertension & Cardiovascular Protection
  • Place of Presentation: Milan, Italy
  • Year and Date: 20130614-17
• [Presentation] 持続的低酸素曝露にともなう心室リモデリングにおけるVEGFの意義と重要性 (2012)
  • Author(s): 禹英喜, 根本慎太郎, 勝間田敬弘, 松村靖夫, 林哲也
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20120920-22
• [Presentation] Effect of hydrogen gas inhalation on lipid metabolism and left ventricular remodeling induced by intermittent hypoxia (2012)
  • Author(s): Nishioka S, Hayashi T, Miyamura M, Mori T, Ukimura A, Okada Y, Ishizaka N, Yoshioka T, Hasegawa K, Matsumura
  • Organizer: ESC Congress 2012
  • Place of Presentation: Munich
  • Year and Date: 20120825-29
• [Presentation] Intermittent hypoxia- induced cardiovascular remodeling in diabetes mellitus (2012)
  • Author(s): Nomura A, Nishioka S, Yamaguchi S, Tagawa A, Furukawa Y, Kato R, Ijiri Y, Matsumura Y, Okada Y, Asahi M, Tanaka K, Hayashi T
  • Organizer: 第35回心筋代謝研究会
  • Place of Presentation: 東京
  • Year and Date: 20120707-08
• [Remarks] 大阪薬科大学循環病態治療学研究室
  • URL: http://www.oups.ac.jp/kenkyu/kenkyuushitu/jyunkanbyoutaitiryo.html