The anesthetic modulation of the protective effect of statin on the endothelium function in diabetic and hypertensive animal models.

• Project/Area Number: 19591815
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Wakayama Medical University
• Principal Investigator: OGAWA Koji Wakayama Medical University, 医学部, 准教授 (30204077)
• Co-Investigator(Kenkyū-buntansha): MIZUMOTO Kazuhiro 和歌山県立医科大学, 医学部, 准教授 (50239258) ; HATANO Yoshio 和歌山県立医科大学, 医学部, 教授 (70115913)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: スタチン / 血管内皮細胞 / 一酸化窒素 / 揮発性麻酔薬 / 糖尿病 / セボフルラン / 弛緩反応

Research Abstract

Exposure of cultured endothelial cells to simvastatin induced NO production. The increase in NO production was significantly inhibited in the presence of sevoflurane. Sevoflurane also inhibited increase in eNOS expression in response to simvastatin, but not eNOSmRNA expression. It is suggested the transcriptional modification of eNOS may be involved in the statin-induced activation of eNOSNO signaling pathways. Sevoflurane appears to affect this process.

Research Products

• [Journal Article] Reduction of adhesion formation by an angiotensin type 1 receptor antagonist. (2011)
  • Author(s): Tokinaga Y, Kimoto Y, Ogawa K, Mizumoto K, Tange K, Hatano Y
  • Journal Title: Langenbecks Arch Surg Volume: 396 Pages: 127-132
  • Peer Reviewed
• [Journal Article] The cellular mechanisms underlying the inhibitory effects of isoflurane and sevoflurane on arginine vasopressin-induced vasoconstriction. (2010)
  • Author(s): Shimogai M, Ogawa K, Tokinaga Y, Yamazaki A, Hatano Y
  • Journal Title: J Anesth 24 Pages: 893-900
  • NAID: 10027741425
  • Peer Reviewed
• [Journal Article] Sevoflurane does not alter norepinephrine-induced intracellular Ca2+ changes in the diabetic rat aorta. (2010)
  • Author(s): Fujii K, Ogawa K, Tokinaga Y, Iranami H, Hatano Y
  • Journal Title: Can J Anesth 57 Pages: 1095-1101
  • Peer Reviewed
• [Journal Article] Differential vasodilation response to olprinone in rabbit renal and common carotid arteries. (2010)
  • Author(s): Minonishi T, Ogawa K, Tokinaga Y, Negoro T, Kimoto Y, Hatano Y
  • Journal Title: J Anesth 24 Pages: 61-66
  • NAID: 10027265635
  • Peer Reviewed
• [Journal Article] Sevoflurane does not alter norepinephrine-induced intracellular Ca^<2+> changes in the diabetic rat aorta (2010)
  • Author(s): Fujii K, Ogawa K, Tokinaga Y, Iranami H, Hatano Y
  • Journal Title: Can J Anesth Volume: 57 Pages: 1095-1101
  • Peer Reviewed
• [Journal Article] The cellular mechanisms underlying the inhibitory effects of isoflurane and sevoflurane on arginine vasopressin-induced vasoconstriction. (2010)
  • Author(s): Shimogai M, Ogawa K, Tokinaga Y, Yamazaki A, Hatano Y
  • Journal Title: J Anesth Volume: 24 Pages: 893-900
  • NAID: 10027741425
  • Peer Reviewed
• [Journal Article] Differential vasodilation response to olprinone in rabbit renal and common carotid arteries (2010)
  • Author(s): Minonishi T, Ogawa K, Tokinaga Y, Negoro T, Kimoto Y, Hatano Y
  • Journal Title: J Anesth 24 Pages: 61-66
  • NAID: 10027265635
  • Peer Reviewed
• [Journal Article] Differential vasodilation response to olprinone in rabbit renal and common carotid arteries (2010)
  • Author(s): Minonishi T, Ogawa K, Tokinaga Y, et al.
  • Journal Title: Journal of Anesthesia 24 Pages: 61-66
  • NAID: 10027265635
  • Peer Reviewed
• [Journal Article] Volatile Anesthetics Inhibit Angiotensin II-induced Vascular Contraction by Modulating Myosin Light Chain Phosphatase Inhibiting Protein, CPI-17 and Regulatory Subunit, MYPT1 Phosphorylation. (2009)
  • Author(s): Qi F, Ogawa K, Tokinaga Y, Uematsu N, Minonishi T, Hatano Y
  • Journal Title: Anesth Analg 109 Pages: 412-417
  • Peer Reviewed
• [Journal Article] Volatile Anesthetics Inhibit Angiotensin II-induced Vascular Contraction by Modulating Myosin Light Chain Phosphatase Inhibiting Protein, CPI-17 and Regulatory Subunit, MYPT1 Phosphorylation (2009)
  • Author(s): Qi Feng, Ogawa K, Tokinaga Y, Uematsu N, Minonishi T, Hatano Y
  • Journal Title: Anesth Analg 109 Pages: 412-417
  • Peer Reviewed
• [Journal Article] Volatile Anesthetics Inhibit Angiotensin II-induced Vascular Contraction by Modulating Myosin Light Chain Phosphatase Inhibiting Protein, CPI-17 and Regulatory Subunit, MYPT1 Phosphorylation (2009)
  • Author(s): Qi Feng, Ogawa K, Tokinaga Y, et al.
  • Journal Title: Anesthesia & Analgesia 109 Pages: 412-417
  • Peer Reviewed
• [Journal Article] Volatile Anesthetics Inhibit Angiotensin II-induced Vascular Contraction by Modulating Myosin Light Chain Phosphatase Inhibiting Protein, CPI-17 and Regulatory Subunit, MYPTl Phosphorylation (2009)
  • Author(s): Qi Feng, Ogawa K, et al.
  • Journal Title: Anesthesia & Analgesia (In press)
  • Peer Reviewed
• [Journal Article] Mechanism of the ropivacaine-induced increase in intracellular Ca2+ concentration in rat aortic smooth muscle. (2007)
  • Author(s): Tokinaga Y, Ogawa K, Yu J, Kuriyama T, Minonishi T, Hatano Y
  • Journal Title: Acta Anaesthsiol Scand 51 Pages: 1155-1160
  • Peer Reviewed
• [Journal Article] The mechanism behind the inhibitory effect of isoflurane on Angiotensin II-induced contraction is different from that of sevoflurane. (2007)
  • Author(s): Ishikawa A, Ogawa K, Tokinaga Y, Uematsu N, Mizumoto K, Hatano Y
  • Journal Title: Anesth Analg 105 Pages: 97-102
  • Peer Reviewed
• [Journal Article] The mechanism behind the inhibitory effect of isoflurane on Angioten sin II-induced contraction is different from that of sevoflurane. (2007)
  • Author(s): Ishikawa A, Ogawa K, Tokinaga Y, Uematsu N, Mizumoto K, Hatano Y
  • Journal Title: Anesth Analg 105 Pages: 97-102
  • Peer Reviewed
• [Journal Article] Effects of isoflurane and sevoflurane anesthesia on arteriovenous shunt flow in the lower limb of diabetic patients without neuropathy. (2007)
  • Author(s): Negoro T, Mizumoto K, Ogawa K, Hironaka Y, Kakutani T, Hatano Y
  • Journal Title: Anesthesiology 107 Pages: 45-52
  • Peer Reviewed
• [Presentation] The Effect of Sevoflurane on Simvastatin-Induced eNOS Expression in Cultured Endothelial Cells. (2010)
  • Author(s): Tange K, Kawashima K, Tokinaga Y, Ogawa K, Hatano Y
  • Organizer: 2010 Annual Meeting of American Society of Anesthesiologists.
  • Place of Presentation: San Diego, USA
  • Year and Date: 2010-10-18
• [Presentation] The Effect of Sevoflurane on Simvastatin-Induced eNOS Expression in Cultured Endothelial Cells. (2010)
  • Author(s): Tange K, Kawashima K, Tokinaga Y, Ogawa K, Hatano Y
  • Organizer: 2010 Annual Meeting of American Society of Anesth esiologists
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2010-10-18
• [Presentation] 急性シンバスタチン投与による一酸化窒素合成酵素発現に及ぼすセボフルランの影響 (2010)
  • Author(s): 丹下和晃、時永泰行、谷奥匡、平井亜葵、小川幸志、畑埜義雄
  • Organizer: 日本麻酔科学会第57回学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2010-06-04
• [Presentation] Simvastatin restores the impaired endothelium-dependent relaxation in diabetic rats. (2009)
  • Author(s): Sugimoto K, Ogawa K, Tokinaga Y, Tange K, Hatano Y
  • Organizer: 2009 Annual Meeting of American Society of Anesthesiologists.
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2009-10-18
• [Presentation] Sevoflurane inhibits the increase in statin-Induced endothelial nitric oxide synthase expression. (2009)
  • Author(s): 丹下和晃, 時永泰行, 小川幸志, 畑埜義雄
  • Organizer: 2009 Annual Meeting of American Society of Anesthesiologists.
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2009-10-18
• [Presentation] Sevoflurane inhibits the increase in statin-Induced endothelial nitric oxide synthase expression (2009)
  • Author(s): Tange K, Tokinaga Y, Ogawa K, Hatano Y
  • Organizer: 2009 Annual Meeting of Anerican Society of Anesthesiologists
  • Place of Presentation: 米国ルイジアナ州ニューオリンズ
  • Year and Date: 2009-10-17
• [Presentation] Simvastatin restores the impaired endothelium-dependent relaxation in diabetic rats (2009)
  • Author(s): Sugimoto K, Ogawa K, Tokinaga Y, Tange K, Hatano Y
  • Organizer: 2009 Annual Meeting of Anerican Society of Anesthesiologists
  • Place of Presentation: 米国ルイジアナ州ニューオリンズ
  • Year and Date: 2009-10-17
• [Presentation] ウシ大動脈内皮細胞における一酸化窒素 (NO) 産生量に対するシンバスタチンの急性効果 (2009)
  • Author(s): 丹下和晃, 時永泰行, 井上真理子, 佐古有希子, 小川幸志, 畑埜義雄
  • Organizer: 日本麻酔科学会第56回学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2009-08-17
• [Presentation] シンバスタチンは糖尿病における内皮依存性弛緩反応低下を回復させる (2009)
  • Author(s): 時永泰行、小川幸志、木本吉紀、槙野仁奈、阪中容、畑埜義雄
  • Organizer: 日本麻酔科学会第56回学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2009-08-16
• [Presentation] ウシ大動脈内皮細胞における一酸化窒素(NO)産生量に対するシンバスタチンの急性効果 (2009)
  • Author(s): 丹下和晃、時永泰行、井上真理子、佐古有希子、小川幸志、畑埜義雄
  • Organizer: 日本麻酔科学会第56回学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2009-08-16
• [Presentation] Acute Effect of Simvastatin on Nitric Oxide Synthesis in Bovine Aortic Endothelial Cells (2008)
  • Author(s): Tange K, Tokinaga Y, Ogawa K, et al.
  • Organizer: 2008 annual meeting of American Society of Anesthesiologist
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 2008-10-21
• [Presentation] Acute effect of simvastatin on nitric oxide synthesis in bovine aortic endothelial cells. (2008)
  • Author(s): Tange K, Tokinaga Y, Ogawa K, Kuriyama T, Hatano Y
  • Organizer: 2008 Annual Meeting of American Society of Anesthesiologists.
  • Place of Presentation: Orlando, USA
  • Year and Date: 2008-10-19
• [Presentation] Volatile anesthetics inhibit AVP-induced vasoconstriction by modulating intracellular Ca2+ and Rho K. (2008)
  • Author(s): Shimogai M, Tokinaga Y, Ogawa K, Iranami H, Hatano Y
  • Organizer: 2008 Annual Meeting of American Society of Anesthesiologists.
  • Place of Presentation: Orlando, USA
  • Year and Date: 2008-10-19
• [Presentation] セボフルランは摘出ラット大動脈のシンバスタチンによる血管弛緩反応を増強する (2008)
  • Author(s): 藤井啓介、小川幸志、時永泰行、岩橋静江、伊良波浩、畑埜義雄
  • Organizer: 日本麻酔科学会第55回学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2008-06-12
• [Presentation] Vasopressin restores the hyporesponsiveness of vascular smooth muscle to norepinephrinee in sepsis. (2007)
  • Author(s): Yamazaki A, Tokinaga Y, Iranami H, Ogawa K, Hatano Y
  • Organizer: Annual meeting of American society of the anesthesiologists
  • Place of Presentation: San Francisco,CA,USA
• [Presentation] Sevoflurane does not alter norepinephrine-induced intracellular Ca2+ change in diabetic rat aorta. (2007)
  • Author(s): Fujii K, Ogawa K, Iranami H, Tokinaga Y, Hatano Y
  • Organizer: Annual meeting of American society of the anesthesiologists
  • Place of Presentation: San Francisco,CA,USA