Neural regulatory mechanisms of cardiopulmonary function in hypoxic conditions.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590242
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: Hiroshima International University
• Principal Investigator: SHIRAI Mikiyasu Hiroshima International University, 心臓生理機能部, 部長 (70162758)
• Co-Investigator(Kenkyū-buntansha): SONOBE Takashi 独立行政法人国立循環器病研究センター, 心臓生理機能部, 流動研究員 (70548289) ; INAMORI Shuji 広島国際大学, 保健医療学部, 講師 (60412334)
• Research Collaborator: JAMES T.Pearson Dept. of Physiology, Monash University ; DARYL O.Schwenke Dept. of Physiology, University of Otago ; 秋山 剛 独立行政法人国立循環器病研究センター, 心臓生理機能部 ; 徳留 健 独立行政法人国立循環器病研究センター, 生化学部 ; 土持 裕胤 独立行政法人国立循環器病研究センター, 心臓生理機能部 ; 吉田 謙一 東京大学, 大学院・医学系研究科・公共健康医学専攻法医学 ; 梅谷 啓二 (財)高輝度光科学研究センター
• Project Period (FY): 2008 – 2010
• Keywords: 低酸素 / 肺高血圧 / 出血性低血圧 / 睡眠時無呼吸症候群 / 心筋梗塞 / グレリン

Research Abstract

Using rat models of acute and chronic hypoxic pulmonary hypertension, acute hemorrhagic hypotension, sleep apnea syndrome and acute myocardial infarction, and M2 muscarinic cholinergic receptor KO mice, this study clarified that the sympathetic nervous system-mediated control of pulmonary vascular tone and heart rate and rhythm is essential to survive under the condition of hypoxia, exercise or cardiac ischemia. Furthermore, this study suggested that ghrelin, which regulates the autonomic nerve function, has cardiopulmonary protective effects in myocardial infarction and pulmonary hypertension.

Research Products

• [Journal Article] Centrally administered ghrelin activates cardiac vagal nerve in anesthetized rabbits. (2011)
  • Author(s): Shimizu S, Akiyama T, Kawada T, Sonobe T, Kamiya A, Shishido T, Tokudome T, Hosoda H, Shirai M
  • Journal Title: Auton.Neurosci. Epub ahead of print
  • Peer Reviewed
• [Journal Article] Imaging on the closed-chest mouse pulmonary circulation using synchrotron radiation micro- angiography. (2011)
  • Author(s): Sonobe T, Schwenke DO, Pearson JT, Yoshimoto M, Fujii Y, Umetani K, Shirai M
  • Journal Title: J.Appl.Physiol. Epub ahead of print
  • Peer Reviewed
• [Journal Article] Docking protein Gab1 is an essential component of postnatal angiogenesis after ischemia via HGF/cmet signaling. (2011)
  • Author(s): Shioyama W, Nakaoka Y, Higuchi K, Minami T, Taniyama Y, Nishida K, Kidoya H, Sonobe T, Naito H, Arita Y, Hashimoto T, Kuroda T, Fujio Y, Shirai M, Takakura N, Morishita R, Yamauchi-Takihara K, Kodama T, Hirano T, Mochizuki N, Komuro I.
  • Journal Title: Circ.Res. 108(6)(Epub) Pages: 664-675
  • Peer Reviewed
• [Journal Article] Role of Rho kinase signaling and endothelial dysfunction in modulating blood flow distribution in pulmonary hypertension. (2011)
  • Author(s): Schwenke, D.O., Pearson, J.T., Sonobe, T., Ishibashi-Ueda H., Shimouchi, A., Kangawa, K. Umetani, K., Shirai, M.
  • Journal Title: J Appl Physiol. 110(4) Pages: 901-8
  • Peer Reviewed
• [Journal Article] Role of Ca^<2+>-activated K+ channels in catecholamine release from in vivo rat adrenal medulla. (2010)
  • Author(s): Akiyama T, Yamazaki T, Kawada T, Shimizu S, Sugimachi M, Shirai M.
  • Journal Title: Neurochem.Int. 56(2) Pages: 263-269
  • Peer Reviewed
• [Journal Article] Large conductance Ca^<2+>-activated K^+ channels inhibit vagal acetylcholine release at the rabbit sinoatrial node. (2010)
  • Author(s): Kawada T, Akiyama T, Shimizu S, Kamiya A, Uemura K, Sata Y, Shirai M, Sugimachi M.
  • Journal Title: Auton.Neurosci. 156(1-2) Pages: 149-151
  • Peer Reviewed
• [Journal Article] Analysis of breath and skin gases emanating during exercise using an original biogas sampling system connected to an atmospheric pressure ionization mass spectrometer. (2010)
  • Author(s): Shimouchi A., Nose, K., Shirai, M.
  • Journal Title: IEEE Sensors J. 10(1) Pages: 85-91
  • Peer Reviewed
• [Journal Article] Exogenous ghrelin accentuates the acute hypoxic ventilatory response after two weeks of chronic hypoxia in conscious rats. (2010)
  • Author(s): Schwenke DO, Pearson JT, Kangawa K, Cragg PA, Shirai M.
  • Journal Title: Acta Physiol 200 Pages: 279-287
  • Peer Reviewed
• [Journal Article] Detection of endogenous acetylcholine release during brief ischemia in the rabbit ventricle : a possible trigger for ischemic preconditioning. (2009)
  • Author(s): Kawada T, Akiyama T, Shimizu S, Kamiya A, Uemura K, Li M, Shirai M, Sugimachi M.
  • Journal Title: Life Sci 85 Pages: 597-601
  • Peer Reviewed
• [Journal Article] Contrast angiography of the renal microcirculation in vivo using synchrotron radiation. (2009)
  • Author(s): Eppel, G.A., Jacono, D.L., Shirai, M., Umetani, K., Evans, R.G., Pearson, J.T.
  • Journal Title: Am.J.Physiol.Renal Physiol. 296 Pages: F1023-F1031
  • Peer Reviewed
• [Journal Article] Changes in pulmonary blood flow distribution in monocrotaline compared with hypoxia-induced models of pulmonary hypertension. (2009)
  • Author(s): Schwenke, D.O., Pearson, J.T., Shimouchi, A., Kangawa, K., Tsuchimochi, H., Umetani, K., Shirai, M., Cragg PA.
  • Journal Title: J Hypertens. 27(7) Pages: 1410-1419
  • Peer Reviewed
• [Journal Article] Synchrotron-based angiography for investigating regulation of vasomotor function in the microcirculation in vivo. (2009)
  • Author(s): Shirai, M., Schwenke, D.O., Eppel, G.A., Evans, R.G., Edgley, A.J., Tsuchimochi, H., Umetani, K., Pearson J.T.
  • Journal Title: (Frontiers in Research Review) Clin.Exp.Pharmacol. Physiol. 36 Pages: 107-116
  • Peer Reviewed
• [Journal Article] Early ghrelin treatment following myocardial infarction prevents an increase in cardiac sympathetic tone and reduces mortality. (2008)
  • Author(s): Schwenke, D.O., Tokudome, T., Kishimoto, I., Horio, T., Shirai, M., Cragg, P.A., Kangawa, K.
  • Journal Title: Endocrinology 149 Pages: 5172-5176
  • Peer Reviewed
• [Journal Article] Changes in macrovessel pulmonary blood flow distribution following chronic hypoxia - assessed using synchrotron radiation microangiography. (2008)
  • Author(s): Schwenke, D.O., Pearson, J.T., Umetani, K., Kangawa, K., Shirai, M.
  • Journal Title: J.Appl.Physiol. 104 Pages: 88-96
  • Peer Reviewed
• [Journal Article] Exogenous ghrelin attenuates the progression of chronic hypoxia-induced pulmonary hypertension in conscious rats. (2008)
  • Author(s): Schwenke D.O., Tokudome, T., Shirai, M., Hosoda, H., Horio, T., Kishimoto, I., Kangawa, K.
  • Journal Title: Endocrinology 149 Pages: 237-244
  • Peer Reviewed
• [Presentation] モノクロタリン肺高血圧ラットでの血管内皮とRho-kinaseの機能障害は肺微小血管レベルで起こる (2011)
  • Author(s): 白井幹康、シュエンキ・ダリル、曽野部崇、藤井豊、吉本光佐、下内章人、寒川賢治、梅谷啓二
  • Organizer: 第88回日本生理学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-29
• [Presentation] グレリンノックアウトマウスでは慢性低酸素負荷で怒る換気適応が減弱する (2011)
  • Author(s): 曽野部崇、シュエンキ・ダリル、徳留健、岸本一郎、寒川賢治、白井幹康
  • Organizer: 第88回日本生理学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-29
• [Presentation] アナフィラキシーショックに対するラット門脈の血管収縮応答 (2011)
  • Author(s): 柳田洋、下内章人、曽野部崇、藤井豊、芝本利重、白井幹康
  • Organizer: 第88回日本生理学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-29
• [Presentation] アンジオテンシンII慢性投与による交感神経活動と動脈圧の変化 (2011)
  • Author(s): 吉本光佐、三木健寿、白井幹康、Osborn John
  • Organizer: 第88回日本生理学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-28
• [Presentation] 心臓交感・副交感神経活動に対するα_2アゴニストの影響 (2010)
  • Author(s): 清水秀二、秋山剛、川田徹、神谷厚範、宍戸稔聡、白井幹康、杉町勝
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-21
• [Presentation] グレリン投与は急性心筋梗塞時の心臓交感神経活動増大と致死率を低下させる (2010)
  • Author(s): 白井幹康、シュエンキ・ダリル、徳留健、岸本一郎、寒川賢治
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-20
• [Presentation] 運動負荷に伴う呼気・皮膚ガス微量成分の動態 (2010)
  • Author(s): 下内章人、野瀬和利、白井幹康
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-20
• [Presentation] In vivo放射光微小血管造影法によるマウス肺循環系の評価 (2010)
  • Author(s): 曽野部崇、シュエンキ・ダリル、ピアーソン・ジェイムズ、梅谷啓二、白井幹康
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-19
• [Presentation] マグネシウム静脈内投与の副腎交感神経節伝達に及ぼす影響 (2010)
  • Author(s): 秋山剛、川田徹、清水秀二、曽野部崇、杉町勝、白井幹康
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-19
• [Presentation] contrast angiography of the rat renal microcirculation in vivo using synchrotron radiation. (2009)
  • Author(s): Shirai M, Eppel GG, Jacono DL, Umetani K, Evans RG, Pearson J
  • Organizer: 36^<th> Inter- national congress of Physiological Sciences
  • Place of Presentation: Kyoto.
  • Year and Date: 2009-08-01
• [Presentation] Dynamic synchrotron imaging of the coronary vasculature in vivo in rat models of heart failure and diabetes. (2009)
  • Author(s): Pearson J, Jenkins MJ, Okura Y, Tani D, Schwenke DO, Umetani K, Kangawa K, Shirai M
  • Organizer: 36^<th> International congress of Physiological Sciences
  • Place of Presentation: Kyoto.
  • Year and Date: 2009-07-30
• [Presentation] Changes in pulmonary blood flow in monocrotaline and hypoxia-induced models of pulmonary hypertension, assessed using synchrotron radiation. (2009)
  • Author(s): Schwenke DO, Pearson JT, Kangawa K, Ymetani, K, Shirai M, Cragg PA.
  • Organizer: 36^<th> International congress of Physiol- ogical Sciences
  • Place of Presentation: Kyoto.
  • Year and Date: 2009-07-29
• [Presentation] The importance of interfilament spacing in the regulation of crossbridge kinetics in the in situ heart. (2009)
  • Author(s): Pearson J, Yagi N, Schwenke DO, Shirai M
  • Organizer: 36^<th> International congress of Physiological Sciences
  • Place of Presentation: Kyoto.
  • Year and Date: 2009-07-28
• [Presentation] 放射光を用いた心血管機能の評価 (2008)
  • Author(s): 白井幹康
  • Organizer: 第152回医用画像情報学会(特別講演)
  • Place of Presentation: 広島
  • Year and Date: 2008-10-04
• [Presentation] シュエンキ・ダリル、ピアーソン・ジェームズ、梅谷啓二 放射光高速微小血管造影法を用いた低酸素性肺循環応答の観察:閉胸ラットを用いて (2008)
  • Author(s): 白井幹康
  • Organizer: 第85回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-03-27
• [Book] 低酸素性血管攣縮(酸素ダイナミクス研究会「からだと酸素の事典」)(高橋英嗣、精山明敏編集) (2009)
  • Author(s): 下内章人, 白井幹康
  • Total Pages: 242-244
  • Publisher: 朝倉書店