THE MECHANISM OF SALT SENSITIVE HYPERTENSION IN INTERMITTENT HYPOXIA

• Project/Area Number: 26461262
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Nihon University
• Principal Investigator: KOYAMA Sayoko 日本大学, 医学部, 助教 (30618202)
• Co-Investigator(Renkei-kenkyūsha): SHIMOSAWA Tatsuo 国際医療福祉大学, 医学部, 教授 (90231365)
• Research Collaborator: Yeerbolati Alimila
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 間欠的低酸素 / 食塩感受性高血圧 / NCC / 高血圧 / ENaC / Dopamine / 11bHSD2 / 食塩感受性

Outline of Final Research Achievements

Intermittent hypoxia (IH) increases membrane protein of NCC (The thiazide-sensitive Na+-Cl－ cotransporter) in Kidney tubles. It remain by salt loading diet. The other Sodium Chrolide channel in Kidney ENaC(Epithelial sodium channel),NHE3(Na+/H+ exchange),NKCC-2(Na-K-Cl cotransporter) were not changed after IH. Challenge test of Amirolide showed no difference between Control and IH group, but Thiazide test showed remarkably increased IH group. These data suggested NCC is key for salt sensitive hypertension by IH.

Research Products

• [Journal Article] Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via β3AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia (2015)
  • Author(s): Hisashi Nagai, Ichiro Kuwahira, Daryl O. Schwenke, Hirotsugu Tsuchimochi, Akina Nara, Sayoko Ogura, Takashi Sonobe, Tadakatsu Inagaki, Yutaka Fujii, Rutsuko Yamaguchi, Lisa Wingenfeld, Keiji Umetani, Tatsuo Shimosawa, Kenichi Yoshida, Koichi Uemura, James T. Pearson, Mikiyasu Shirai
  • Journal Title: PLoS ONE Volume: 10 Issue: 7 Pages: 1-20
  • DOI: 10.1371/journal.pone.0131923
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pulmonary Arterial Hypertension in Rats Due to Age-related Arginase Activation in Intermittent Hypoxia. (2015)
  • Author(s): Nara A, Nagai H, Shintani-Ishida K, Ogura S, Shimosawa T, Kuwahira I, Shirai M, Yoshida KI.
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology. Volume: 未定 Issue: 2 Pages: 184-184
  • DOI: 10.1165/rcmb.2014-0163oc
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] High-salt in addition to high-fat diet may enhance inflammation and fibrosis in liver steatosis induced by oxidative stress and dyslipidemia in mice (2015)
  • Author(s): Yuzaburo Uetake, Hitoshi Ikeda, Rie Irie, Kazuaki Tejima, Hiromitsu Matsui, Sayoko Ogura, Hong Wang, ShengYu Mu, Daigoro Hirohama, Katsuyuki Ando, Tatsuya Sawamura, Yutaka Yatomi, Toshiro Fujita, Tatsuo Shimosawa
  • Journal Title: Lipids in Health and Disease Volume: 14 Issue: 1 Pages: 6-6
  • DOI: 10.1186/s12944-015-0002-9
  • Open Access
• [Journal Article] Pulmonary Arterial Hypertension in Rats Due to Age-related Arginase Activation in Intermittent Hypoxia. (2014)
  • Author(s): Nara A, Nagai H, Shintani-Ishida K, Ogura S, Shimosawa T, Kuwahira I, Shirai M, Yoshida KI.
  • Journal Title: Am J Respir Cell Mol Biol. Volume: epub Issue: 8 Pages: 452-452
  • DOI: 10.1007/s11906-014-0452-x
  • Peer Reviewed / Open Access
• [Journal Article] Beta2-adrenergic receptor-dependent attenuation of hypoxic pulmonary vasoconstriction prevents progression of pulmonary arterial hypertension in intermittent hypoxic rats (2014)
  • Author(s): Hisashi Nagai, Ichiro Kuwahira, Daryl O. Schwenke, Hirotsugu Tsuchimochi, Akina Nara, Tadakatsu Inagaki, Sayoko Ogura, Yutaka Fujii, Keiji Umetani, Tatsuo Shimosawa, Kenichi Yoshida, James T. Pearson, Koichi Uemura, Mikiyasu Shirai
  • Journal Title: PLOS ONE Volume: 10 Issue: 10 Pages: 1-10
  • DOI: 10.1371/journal.pone.0110693
  • Peer Reviewed / Open Access
• [Presentation] High salt diet increases Prostaglandin E2 Synthesis thorugh oxidative stress (2018)
  • Author(s): Rehaman Latapati, 森典子、広浜大五郎、小倉彩世子、王 聡彗、Alimila Yeerbolati,、Liu Beibei、藤田敏郎、矢富裕、下澤達雄
  • Organizer: 第22回日本心血管内分泌代謝学会学術総会
• [Presentation] The mechanism of Salt-sensitive Hypertension in Intermittent Hypoxia (2018)
  • Author(s): Alimila Yeerbolati, Sayoko Ogura, Latapati Reheman,Tatsuo Shimosawa
  • Organizer: 第61回日本腎臓病学会 Asian Session Program
• [Presentation] THE mechanism of salt sensitive hypertension in intermittent hypoxia (2017)
  • Author(s): Alimila Yeerbolati, Sayoko Ogura, Latapati Reheman,Tatsuo Shimosawa
  • Organizer: 第40回日本高血圧学会総会
• [Presentation] Oxidative stress responsible for saltinducedPGE2 expression (2017)
  • Author(s): Latapati Reheman，Fumio Kawakami Mori，Yukihisa Murata，Tatsuro Nakamura，Sayoko Ogura，Yutaka Yatomi，Tatsuo Shimosawa
  • Organizer: 第34回国際心臓研究学会日本部会
• [Presentation] Low Dose N-nitro-L-arginide MethylEser(L-NAME) causes Salt sensitive Hypertension via Activation of Na+ Cl- Cotransporter (NCC) (2017)
  • Author(s): Conghui Wang, Reheman Latapati, Sayoko Ogura, Suangsung Koid, Fumiko Mori, Tatsuo Shimosawa
  • Organizer: 第40回日本高血圧学会総会
• [Presentation] Low Dose LNAME Causes Salt Sensitive Hypertension via Activation of NCC. (2017)
  • Author(s): Conghui Wang, Reheman Latapati, Sayoko Ogura, Suangsuang Koid, Fumiko Mori, Tastuo Shimosawa
  • Organizer: AHA Council on HypertensionAHA Council on Kidney in Cardiovascular DiseaseAmerican Society of HypertensionJoint Scientific Sessions 2017
  • Int'l Joint Research
• [Presentation] LC/MS解析による血中CRP複合体についての検討 (2017)
  • Author(s): 小倉彩世子、下澤達雄、中山智祥
  • Organizer: 第21回 日本心血管内分泌代謝学会学術総会
• [Presentation] Low dose L-NAME causes salt sensitive hypertension via activation of NCC. (2017)
  • Author(s): Conghui Wang, Suang Suang Koid, Sayoko Ogura, Fumiko Mori, Daigoro Hirohama, Latapati Reheman, Alimila Yeerbolati, Beibei Liu, Tatsuo Shimosawa
  • Organizer: 心血管代謝週間CVMW 2017
• [Presentation] THE MECHANISM OF SALT SENSITIVE HYPERTENSION IN INTERMITTENT HYPOXIA (2016)
  • Author(s): Alimila Yeerbolati,Sayoko Ogura, Latapati Reheman,Conghui Wang, BeiBei Liu, Ichiro Kuwahira, Mikiyasu Shirai, Tatsuo Shimosawa, Toshiro Fujita
  • Organizer: The 26th Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Seoul (Korea)
  • Year and Date: 2016-09-24
  • Int'l Joint Research
• [Presentation] 睡眠時無呼吸症候群における食塩感受性高血圧のメカニズム解明 (2015)
  • Author(s): 小倉彩世子、Wang Conghui, Liu BeiBei, Yeerbolati Alimila, Rehaman Latapati、下澤達雄、藤田敏郎
  • Organizer: 第19回 日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2015-12-11
• [Presentation] 高血圧モデルでの利尿剤による腎保護効果 (2015)
  • Author(s): Rehaman Latapati, 王 聡彗、小倉彩世子、広浜大五郎、下澤達雄、矢富裕
  • Organizer: 第19回 日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2015-12-11
• [Presentation] 睡眠時無呼吸症候群における食塩感受性高血圧のメカニズム解明 (2015)
  • Author(s): 小倉彩世子, Wang Conghui, Liu Beibei, Yeerbolati Alimila,Reheman Latapati , 広浜大五郎, 丸茂丈史, 下澤達雄, 藤田敏郎
  • Organizer: 第38回 日本高血圧学会総会
  • Place of Presentation: 愛媛県県民文化会館（愛媛県・松山市）
  • Year and Date: 2015-10-10
• [Presentation] 食塩負荷慢性心不全および腎不全ラットにたいするトラセミドvsフロセミドの抗アルドステロン作用の比較 (2015)
  • Author(s): Rehaman Latapati、王 聡彗、広浜大五郎、小倉彩世子、森典子、下澤達雄、矢富裕、藤田敏郎
  • Organizer: 第38回 日本高血圧学会総会
  • Place of Presentation: 愛媛県県民文化会館（愛媛県・松山市）
  • Year and Date: 2015-10-10
• [Presentation] 間歇的低酸素による肺高血圧に対するM1 マクロファージの影響 (2014)
  • Author(s): 永井恒志、桑平一郎、奈良明奈、小倉彩世子、下澤達雄、吉田謙一、上村公一、白井幹康
  • Organizer: 第二回肺高血圧学会・第三回肺循環学会合同学術集会
  • Place of Presentation: 大手町サンケイプラザ（東京都千代田区）
  • Year and Date: 2014-10-03
• [Presentation] TORASEMIDE DUAL BLOCKADE OF ALDOSTERONE AND SODIUM CHANNEL IN RENAL FAILURE -INDUCED HEART FAILURE. (2014)
  • Author(s): L. Reheman, D. Hirohama, S. Mu, S. Ogura, F. Mori, C. Wang, Y. Uetake, Y. Yatomi, T. Fujita, T. Shimosawa
  • Organizer: Joint meeting ISH and ESH
  • Place of Presentation: Athens (Greek)
  • Year and Date: 2014-07-15 – 2014-07-19
• [Presentation] RENAL DENERVATION ATTENUATES CARDIAC DIASTOLIC DYSFUNCTION THROUGH SPECIFIC RESTORATION OF SERCA2A (2014)
  • Author(s): D. Hirohama , F. Mori, S. Ogura, S. Mu, Y. Uetake, R. Jimbo, L. Reheman, C. Wang, Y. Yatomi, T. Fujita, M. Nangaku, T. Shimosawa
  • Organizer: Joint meeting ISH and ESH
  • Place of Presentation: Athens (Greek)
  • Year and Date: 2014-07-15 – 2014-07-19
• [Presentation] Different patterns of coronary microvascular function induced by type 1 diabetes and intermittent hypoxia in rats. (2014)
  • Author(s): Ogura, S., Shimosawa, T., Nagai H., Nara A., Kuwahira I., Yoshida K., Shirai M.
  • Organizer: Frontiers in CardioVascular Biology.
  • Place of Presentation: Balcerona (Spain)
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] 自立神経調節と腎臓-心腎連関における効果器と受容器としての働き (2014)
  • Author(s): 下澤達雄、広浜大五郎、Rcheman Latapati,、王慧、森典子、小倉彩世子
  • Organizer: 第87回日本内分泌学会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2014-04-24 – 2014-04-26