Analysis of cerebral microcirculatory regulation in relation to anesthetics and gene therapy using the live-cell imaging

• Project/Area Number: 19390409
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Wakayama Medical University
• Principal Investigator: KINOSHITA Hiroyuki Wakayama Medical University, 医学部, 准教授 (70291490)
• Co-Investigator(Kenkyū-buntansha): MATSUDA Naoyuki 名古屋大学, 大学院・医学研究科, 教授 (50332466) ; NAKAHATA Katsutoshi 和歌山県立医科大学, 医学部, 助教 (70332971) ; HATANO Yoshio 和歌山県立医科大学, 医学部, 教授 (70115913) ; 中畑 克俊 和歌山県立医科大学, 医学部, 助教 (00405416)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2010: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2009: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2008: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2007: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 麻酔学 / 脳スライス / スーパーオキシド / 一酸化窒素 / プロポフォール / NMDA / 電気刺激 / 20HETE / 一酸化窒素合成酵素

Research Abstract

We employed the computer-assisted microscopy to evaluate microvascular function in the rat brain slices. Electrical stimulation induced constriction of the cerebral parenchymal arteriole, whereas an inhibitor of 20-HETE abolished this response. NMDA, which is one of excitatory amino acids, produced dilation of these arterioles, corresponding with intracellular production of superoxide in addition to nitric oxide in the smooth muscle cells. Propofol within clinically relevant concentrations reduced these vascular responses.

Research Products

• [Journal Article] 『静脈麻酔薬の作用機序:受容体と細胞内シグナル伝達機構』プロポフォール (2011)
  • Author(s): 木下浩之
  • Journal Title: Anesthesia 21 Century 2011 13 Pages: 4-10
• [Journal Article] 酸化ストレスからみた臓器保護:心不全と酸化ストレス (2011)
  • Author(s): 木下浩之
  • Journal Title: 日本臨床麻酔学会雑誌 31 Pages: 116-123
  • NAID: 10027753115
  • Peer Reviewed
• [Journal Article] ホスファチジルイノシトール3-キナーゼ-Akt 経路と血管病態生理 (2010)
  • Author(s): 木下浩之
  • Journal Title: Anesthesia 21 Century 12 Pages: 2309-2316
• [Journal Article] The modulation of vascular ATP-sensitive K^+ channel function via phosphatidylinositol 3-kinase-Akt pathway activated by phenylephrine. (2010)
  • Author(s): Haba M, Hatakeyama N, Kinoshita H, Teramae H, Azma T, Hatano Y, Matsuda N
  • Journal Title: J Pharmacol Exp Ther 334 Pages: 673-678
  • Peer Reviewed
• [Journal Article] 血管への酸化ストレスと麻酔薬 (2009)
  • Author(s): 木下浩之
  • Journal Title: 麻酔 58
  • Peer Reviewed
• [Journal Article] The beneficial effect of propofol on arterial adenosine triphosphate-sensitive K^+ channel function impaired by thromboxane. (2009)
  • Author(s): Haba M, Kinoshita H, Matsuda N, Azma T, Hama-Tomioka K, Hatakeyama N, Yamazaki M, Hatano Y
  • Journal Title: Anesthesiology 111 Pages: 279-286
  • Peer Reviewed
• [Journal Article] The role of 20-hydroxyeicosatetraenoic acid in cerebral arteriolar constriction and the inhibitory effect of propofol. (2009)
  • Author(s): Hama-Tomioka K, Kinoshita H, Azma T, Nakahata K, Matsuda N, Hatakeyama N, Kikuchi H, Hatano Y
  • Journal Title: Anesth Analg 109 Pages: 1935-1942
  • Peer Reviewed
• [Journal Article] The beneficial effect of propofol on arterial adenosine triphosphate-sensitive K^+ channel function impaired by thromboxane (2009)
  • Author(s): Haba M, Kinoshita H, Matsuda N, Azma T, Hama-Tomioka K, Hatakeyama N, Yamazaki M, Hatano Y
  • Journal Title: Anesthesiology 111 Pages: 279-286
  • Peer Reviewed
• [Journal Article] The role of 20-hydroxyeicosatetraenoic acid in cerebral arteriolar constriction and the inhibitory effect of propofol (2009)
  • Author(s): Hama-Tomioka K, Kinoshita H, Azma T, Nakahata K, Matsuda N, Hatakeyama N, Kikuchi H, Hatano Y
  • Journal Title: Anesth Analg 109 Pages: 1935-1942
  • Peer Reviewed
• [Journal Article] The beneficial effect of propofol on arterial adenosine trip hosphate-sensitive K^+ channel function impaired by thromboxane (2009)
  • Author(s): Haba M, Kinoshito H, et al.
  • Journal Title: Anesthesiology 111 Pages: 279-286
  • Peer Reviewed
• [Journal Article] The role of 20-hydroxyeicosatetraenoic acid in cerebral arteriolar constriction and the inhibitory effect of propofol (2009)
  • Author(s): Hama-Tomioka K, Kinoshita H, et al.
  • Journal Title: Anesth Analg 109 Pages: 1935-1942
  • Peer Reviewed
• [Journal Article] Propofol restores brain microvascular function impaired by high glucose via the decrease in oxidative stress. (2008)
  • Author(s): Nakahata K, Kinoshita H, Azma T, Matsuda N, Hama-Tomioka K, Haba M, Hatano Y
  • Journal Title: Anesthesiology 108 Pages: 269-275
  • Peer Reviewed
• [Journal Article] Cholinesterase inhibitor donepezil dilates cerebral parenchymal arterioles via the activation of neuronal nitric oxide synthase. (2008)
  • Author(s): Nakahata K, Kinoshita H, Hama-Tomioka K, Ishida Y, Matsuda N, Hatakeyama N, Haba M, Kondo T, Hatano Y
  • Journal Title: Anesthesiology 109 Pages: 124-129
  • Peer Reviewed
• [Journal Article] Propofol restores brain microvascular function impaired by high glucose via the decrease in oxidative stress (2008)
  • Author(s): Nakahata K, Kinoshita H, Azma T, Matsuda N, Hama-Tomioka K, Haba M, Hatano Y
  • Journal Title: Anesthesiology 108 Pages: 269-275
  • Peer Reviewed
• [Journal Article] Cholinesterase inhibitor donepezil dilates cerebral parenchymal arterioles via the activation of neuronal nitric oxide synthase (2008)
  • Author(s): Nakahata K, Kinoshita H, Hama-Tomioka K, Ishida Y, Matsuda N, Hatakeyama N, Haba M, Kondo T, Hatano Y
  • Journal Title: Anesthesiology 109 Pages: 124-129
  • Peer Reviewed
• [Journal Article] Propofol restores brain microvascular function impaired by high glucose via the decrease in oxidative stress. (2008)
  • Author(s): Nakahata K, Kinoshita H, et al.
  • Journal Title: Anesthesiology 108 Pages: 269-275
  • Peer Reviewed
• [Journal Article] Cholinesterase inhibitor donepezil dilates cerebral parenchyma1 arterioles via the activation of neuronal nitric oxide synthase. (2008)
  • Author(s): Nakahata K, Kinoshita H, et al.
  • Journal Title: Anesthesiology 109 Pages: 124-129
  • Peer Reviewed
• [Journal Article] Roles of PI3K-Akt and NADPH oxidase in ATP-sensitive F^+ channe1 function impaired by high glucose in the human artery. (2008)
  • Author(s): Kinoshita H, Matsuda N, et al.
  • Journal Title: Hypertension 52 Pages: 507-513
  • Peer Reviewed
• [Journal Article] Sevoflurane,but not propofol,prevents Rho kinase-dependent contraction induced by sphingosylphosphorylcholine in the porcine coronary artery. (2007)
  • Author(s): Kinoshita H, Matsuda N, Kimoto Y, Tohyama S, Hama K, Nakahata K, Hatano Y
  • Journal Title: Anesthesia and Analgesia 105 Pages: 325-329
  • Peer Reviewed
• [Presentation] Roles of oxidative stress and propofol in cerebral microvessel dilation via NMDA receptors. (2010)
  • Author(s): Hama-Tomioka K, Kinoshita H, Nakahata K, Hatakeyama N, Hatano Y
  • Organizer: 2010 Annual Meeting of American Society of Anesthesiologist
  • Place of Presentation: San Diego, CA, USA
• [Presentation] The role of NMDA receptors in rat cerebral microvessel dilation and the inhibitory effect of propofol (2010)
  • Author(s): Hama-Tomioka K, Kinoshita H, Hatano H
  • Organizer: 2010 Annual Meeting of the International Anesthesia Research Society
  • Place of Presentation: Honolulu, Hawaii, USA
• [Presentation] Roles of oxidative stress and propofol in cerebral microvessel dilation via NMDA receptors (2010)
  • Author(s): Hama-Tomioka K, Kinoshita H, Nakahata K, Hatakeyama N, Hatano Y
  • Organizer: 2010 Annual Meeting of American Society of Anesthesiologist
  • Place of Presentation: San Diego, CA, USA
• [Presentation] The Role of Superoxide in 20-HETE-Induced Vasoconstriction and the Effect of Propofol in the Brain (2009)
  • Author(s): Kinoshita H, Hatakeyama N, Hatano Y
  • Organizer: 2009 Annual Meeting of American Society of Anesthesiologist
  • Place of Presentation: New Orleans, LA, USA
• [Presentation] The Role of Superoxide in 20-HETE-Induced Vasoconstriction and the Effect of Propofol in the Brain (2009)
  • Author(s): Kinoshita H, Hatakeyama N, Hatano Y
  • Organizer: Annual Meeting of American Society of Anesthesiologist
  • Place of Presentation: New Orleans, LA, USA
• [Presentation] The inhibitory effect of propofol on the cerebral microvessel function via neurovascular coupling (2008)
  • Author(s): Hama-Tomioka k, Kinoshita H, Nakahata K, Hatakeyama N, Hatano Y
  • Organizer: 2008 Annual Meeting of American Society of Anesthesiologist
  • Place of Presentation: Orlando, FL, USA
• [Presentation] The role of 20-HETE in the cerebral microvessel function as consequences of neurovascular coupling (2008)
  • Author(s): Hama-Tomioka K, Kinoshita H, Nakahata K, Hatakeyama N, Hatano Y
  • Organizer: 2008 Annual Meeting of American Society of Anesthesiologist
  • Place of Presentation: Orlando, FL, USA
• [Presentation] The inhibitory effect of propofol on the cerebral microvessel function via neurovascular coupling (2008)
  • Author(s): Hama-Tomioka k, Kinoshita H, Nakahata K, Hatakeyama N, Hatano Y
  • Organizer: Annual Meeting of American Society of Anesthesiologist
  • Place of Presentation: Orlando, FL, USA
• [Presentation] The role of 20-HETE in the cerebral microvessel function as consequences of neurovascular coupling (2008)
  • Author(s): Hama-Tomioka K, Kinoshita H, Nakahata K, Hatakeyama N, Hatano Y
  • Organizer: Annual Meeting of American Society of Anesthesiologist
  • Place of Presentation: Orlando, FL, USA
• [Presentation] The role of PI3K-Akt in human vascular ATP-sensi tive K^+ channel function modified by high glucose. (2008)
  • Author(s): Kinoshita H, et al
  • Organizer: Annual Meeting of American Society of Anest hesiologist
  • Place of Presentation: Orlando, FL, USA
• [Presentation] Constriction Followed by Dilation of Cerebral Microvessels as Consequences of Neurovascular Coupling (2007)
  • Author(s): Hama-Tomioka K, Kinoshita H, Nakahata K, Nakata R, Hatano Y
  • Organizer: 2007 Annual Meeting of American Society of Anesthesiologist
  • Place of Presentation: San Francisco, CA, USA
• [Presentation] Constriction Followed by Dilation of Cerebral Microvessels as Consequences of Neurovascular Coupling (2007)
  • Author(s): Hama-Tomioka K, Kinoshita H, Nakahata K, Nakata R, Hatano Y
  • Organizer: Annual Meeting of American Society of Anesthesiologist
  • Place of Presentation: San Francisco, CA, USA
• [Book] 1.局所麻酔薬中毒の薬理-B.心筋と血管平滑筋-局所麻酔薬中毒・アレルギー (2008)
  • Author(s): 木下浩之
  • Publisher: 克誠堂出版
• [Book] 1. 局所麻酔薬中毒の薬理-B. 心筋と血管平滑筋- 局所麻酔薬中毒・アレルギー (2008)
  • Author(s): 木下浩之
  • Publisher: 克誠堂出版
• [Remarks] ホームページ等
  • URL: http://www.wakayama-med.ac.jp/med/anesthesiology/index.html