Mechanisms of diabetic large vascular dysfunction : Focus on vascular contractility

• Project/Area Number: 19790195
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General pharmacology
• Research Institution: Kitasato University
• Principal Investigator: YAMAWAKI Hideyuki Kitasato University, 獣医学部, 講師 (60399607)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 血管平滑筋 / 血管内皮 / 糖尿病 / 高血圧 / 糖尿病高血圧

Research Abstract

本研究課題の目的は、糖尿病性大血管障害の機序を解明し、新規治療法を探索することであり、とりわけ血管反応性に着目した検討を計画した。このために新規糖尿病性大血管障害促進因子として我々が提唱する糖代謝産物であるメチルグリオキサルおよび糖尿病治療薬の血管反応性に及ぼす直接作用を重点的に検討した。そして、メチルグリオキサルが血管平滑筋に直接作用して収縮抑制作用を持つことを初めて明らかにするとともにその機序も解明した。また、II型糖尿病治療薬であるピオグリタゾンが血管組織に直接作用して血管拡張作用を起こす機序も明らかにした。

Research Products

• [Journal Article] Methylglyoxal Inhibits Smooth Muscle Contraction in Isolated Blood Vessels. (2009)
  • Author(s): Mukohda M, Yamawaki H, Nomura H, Okada M, and Hara Y.
  • Journal Title: J Pharmacol Sci 109 Pages: 305-310
  • NAID: 10025734753
  • Peer Reviewed
• [Journal Article] Methylglyoxal inhibits smooth muscle contraction in isolated blood vessels (2009)
  • Author(s): Mukohda
  • Journal Title: J Pharmacol Sci 109 Pages: 305-310
  • Peer Reviewed
• [Journal Article] Methylglyoxal mediates vascular inflammation via JNK and p38 in human endothelial cells. (2008)
  • Author(s): Yamawaki H, Saito K, Okada M, and Hara Y.
  • Journal Title: Am J Physiol Cell Physiol 295
  • Peer Reviewed
• [Journal Article] Mechanisms underlying pioglitazone-mediated relaxation in isolated blood vessel. (2008)
  • Author(s): Nomura H, Yamawaki H, Mukohda M, Okada M, and Hara Y.
  • Journal Title: J Pharmacol Sci 108 Pages: 258-265
  • NAID: 10024592922
  • Peer Reviewed
• [Journal Article] Telmisartan inhibits methylglyoxal-mediated cell death in human vascular endothelium. (2008)
  • Author(s): Baden T, Yamawaki H, Saito K, Mukohda M, Okada M, and Hara Y.
  • Journal Title: Biochem Biophys Res Commun 373 Pages: 253-257
  • Peer Reviewed
• [Journal Article] Methylglyoxal mediates vascular inflammation via JNK and p38 in human endothelial cells (2008)
  • Author(s): H. Yamawaki
  • Journal Title: Am J Physiol Cell Physiol 295
  • Peer Reviewed
• [Journal Article] Telmisartan inhibits methylglyoxal-mediated cell death in human vascular endothelium (2008)
  • Author(s): T. Baden
  • Journal Title: Biochem Biophys Res Commun 373 Pages: 253-257
  • Peer Reviewed
• [Journal Article] Mechanisms underlying pioglitazone-mediated relaxation in isolated blood vessel (2008)
  • Author(s): H. Nomura
  • Journal Title: J Pharmacol Sci 108 Pages: 258-265
  • Peer Reviewed
• [Journal Article] Glyoxal causes inflammatory injury in human endothelial cells (2008)
  • Author(s): H. Yamawaki
  • Journal Title: Biochemical and Biophysical Research Communications
  • Peer Reviewed
• [Presentation] Methylglyoxal enhances sodium nitroprusside?induced relaxation in isolated blood vessel (2009)
  • Author(s): 向田昌司
  • Organizer: 第82回日本薬理学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-03-16
• [Presentation] Methylglyoxal enhances sodium nitroprusside-induced relaxation in isolated blood vessel (2009)
  • Author(s): 向田昌司、山脇英之、岡田宗善、原幸男
  • Organizer: 第82回日本薬理学会総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 糖変性物質メチルグリオキサルの血管反応性におよぼす影響 (2008)
  • Author(s): 山脇 英之
  • Organizer: 第145回日本獣医学会学術集会
  • Place of Presentation: 麻布大学
  • Year and Date: 2008-03-28
• [Presentation] Mechanisms underlying the vasodilating effects of pioglitazonein isolated blood vessel (2008)
  • Author(s): H. Yamawaki
  • Organizer: The 81st Annual Meeting of the Japanese Pharmacological Society
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2008-03-17
• [Presentation] 糖代謝物質の血管内皮障害作用機序の検討 (2008)
  • Author(s): 山脇英之、斎藤和晃、馬殿達也、向田昌司岡田宗善、原幸男
  • Organizer: 第59回日本薬理学会北部会
  • Place of Presentation: 東北大学
• [Presentation] メチルグリオキサルのラット動脈標本収縮性に及ぼす影響 (2008)
  • Author(s): 向田昌司、山脇英之、野村秀美、岡田宗善、原幸男
  • Organizer: 第59回日本薬理学会北部会
  • Place of Presentation: 東北大学
• [Presentation] テルミサルタンはメチルグリオキサルが引き起こすヒト血管内皮細胞におけるアポトーシスを抑制する (2008)
  • Author(s): 馬殿達也、山脇英之、斎藤和晃、向田昌司、岡田宗善、原幸男
  • Organizer: 第146回日本獣医学会
  • Place of Presentation: 宮崎大学