The role of brain Na sensitivity in sympathetic hyperactivation in heart failure

• Project/Area Number: 19890148
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyushu University
• Principal Investigator: ITO Koji Kyushu University, 医学研究院, 研究員 (10452757)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,075,000 (Direct Cost: ¥2,670,000、Indirect Cost: ¥405,000); Fiscal Year 2008: ¥1,755,000 (Direct Cost: ¥1,350,000、Indirect Cost: ¥405,000); Fiscal Year 2007: ¥1,320,000 (Direct Cost: ¥1,320,000)
• Keywords: 食塩摂取 / 心不全(高血圧性心臓病) / 交感神経活動 / 脳 / 脳内Na感受性 / 交感神経活性亢進 / 食塩 / ENaC / 圧負荷心不全 / Rho / Rho-kinase系

Research Abstract

研究代表者である伊藤浩司は、今回の研究において、心不全モデル(腹部大動脈bandingによる圧負荷モデル)において、遺伝的に食塩感受性を有さないにも拘らず、食塩摂取に対する交感神経活動の上昇や脳室内高Na投与に対する血圧、心拍数、交感神経活動の上昇が対照群に比べて有意に増強し、結果的に心機能の低下が進行することを明らかにした。さらに、その食塩摂取に対する交感神経活動亢進の機序として、脳内Rho-kinase系→上皮型Naチャネルの機能亢進が関与することを明らかにした。本研究成果は、心不全患者(特に高血圧性心臓病など)における食塩過剰摂取による心不全増悪の機序を解明し、心不全治療の新たなターゲットを提唱する学問的にも社会的にも意義の大きいものと考えられ、循環器系トップジャーナルであるCirculation Research誌に受理された。

Research Products

• [Journal Article] Acquisition of brain Na sensitivity contributes to salt-induced sympathoexcitation and cardiac dysfunction in mice with pressure overload (2009)
  • Author(s): Ito K, Hirooka Y, Sunagawa K
  • Journal Title: Circulation Research 104 Pages: 1004-1011
  • Peer Reviewed
• [Journal Article] Acquisition of brain Na sensitivity contributes to salt-induced sympatho excitation and cardiac dysfunction in mice with pressure overload. (2009)
  • Author(s): Ito K, et al.
  • Journal Title: Circulation Research 104(in press)
  • Peer Reviewed
• [Presentation] Enhanced brain Na sensitivity contributes to salt-induced sympathetic hyperactivation and deterioration of cardiac function in mice with LVH (2009)
  • Author(s): Ito K, et.al.
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪市(日本)
  • Year and Date: 2009-03-20
• [Presentation] Enhanced brain Na sensitivity contributes to salt-induced sympathetic hyper activation and deterioration of cardiac function in mice with LVH. (2009)
  • Author(s): Ito K, et al.
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-03-20
• [Presentation] High-salt intake superimposed on left ventricular hypertrophy activates brain ENaC and leads to sympathetic hyperactivation and ventricular dysfunction (2008)
  • Author(s): Ito K, et.al.
  • Organizer: American Heart Association (AHA) 2008 Scientific Session
  • Place of Presentation: ニューオリンズ市(アメリカ)
  • Year and Date: 2008-11-10
• [Presentation] High-salt intake superimposed on left ventricular hypertrophy activates brain ENaC and leads to sympathetic hyperactivation and ventricular dysfunction. (2008)
  • Author(s): Ito K, et al.
  • Organizer: American Heart Association (AHA)2008 Scientific Sessions
  • Place of Presentation: ニューオリンズ市(アメリカ)
  • Year and Date: 2008-11-10
• [Presentation] 圧負荷左室肥大モデルで高食塩負荷がもたらす左心機能低下に脳内ENaCを介したNa感受性亢進によって生じる交感神経活性化が関与する (2008)
  • Author(s): 伊藤浩司, ほか
  • Organizer: 第31回日本高血圧学会総会
  • Place of Presentation: 札幌市(日本)
  • Year and Date: 2008-10-11
• [Presentation] 圧負荷左室肥大モデルで高食塩負荷がもたらす左心機能低下に脳内EN_aCを介したN_a感受性完進によって生じる交感神経活性化が関与する (2008)
  • Author(s): 伊藤浩司
  • Organizer: 第31回日本高血圧学会総会
  • Place of Presentation: 札幌市
  • Year and Date: 2008-10-11
• [Presentation] Blockade of brain ENaC attenuated high salt induced cardiac dysfunction of hypertrophied heart via the attenuation of sympathetic activation (2008)
  • Author(s): Ito K, et.al.
  • Organizer: International Society of Hypertension (ISH)2008
  • Place of Presentation: ベルリン市(ドイツ)
  • Year and Date: 2008-06-17
• [Presentation] Blockade of brain ENaC attenuated high salt induced cardiac dysfunction of hypertrophied heart via the attenuation of sympathetic activation. (2008)
  • Author(s): Ito K, et al.
  • Organizer: International Society of Hypertension (ISH) 2008
  • Place of Presentation: ベルリン市(ドイツ)
  • Year and Date: 2008-06-17
• [Presentation] High salt intake deteriorates cardiac function of hypertrophied heart, Possibly via the excessive sympathetic drive (2008)
  • Author(s): Ito K, et.al.
  • Organizer: Experimental Biology 2008
  • Place of Presentation: サンディエゴ市(アメリカ)
  • Year and Date: 2008-04-06
• [Presentation] High salt intake deteriorates cardiac function of hypertrophied heart, Possibly via the excessive sympathetic drive. (2008)
  • Author(s): Ito K, et al.
  • Organizer: Experimental Biology 2008
  • Place of Presentation: サンデイェゴ市(アメリカ)
  • Year and Date: 2008-04-06