北里大学 獣医学部 獣医学科 研究室

北里大学獣医学部

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獣医学科 獣医薬理学研究室

トップ 学科・大学院案内 獣医学科獣医学科 獣医薬理学研究室

生体機構系 獣医解剖学研究室獣医生理学研究室
獣医生化学研究室獣医薬理学研究室
毒性学研究室獣医病理学研究室
実験動物学研究室
予防衛生系 獣医微生物学研究室人獣共通感染症学研究室
獣医伝染病学研究室獣医衛生学研究室
獣医公衆衛生学研究室獣医寄生虫学研究室
臨床系 獣医臨床繁殖学研究室大動物臨床学研究室
小動物第1内科学研究室小動物第2内科学研究室
小動物第1外科学研究室小動物第2外科学研究室
獣医放射線学研究室

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研究室名(フリガナ) 獣医薬理学(ジュウイヤクリガク)
学科 獣医学科
生体機構系
研究室URL http://www2.vmas.kitasato-u.ac.jp/pharmacology/
スタッフ [教   授] 山脇 英之
[准教授] 岡田 宗善
研究内容 循環薬理学が主な研究分野である。血圧記録、収縮張力測定法、パッチクランプ法など生理学的手法に加えて,生化学的・分子生物学的手法を組み合わせることで循環器疾患の病態生理を明らかにするとともに,循環器作用薬の作用発現機構の解明を目指している。現在、研究室では丸ごとの動物を使った実験(高血圧・心不全モデル動物の血圧記録や組織学的検討)、心・血管組織を使った張力測定、心臓の細胞を使った電気生理学的実験、、培養細胞(血管内皮・平滑筋細胞、心繊維芽細胞、心筋細胞)を使った細胞生物学的実験(細胞内情報伝達機構の解明)が行われている。
研究課題 ・高血圧、心不全、動脈硬化、糖尿病性血管障害の病態機序解明と治療薬の探索:心血管生物学的検討
・新規脂肪組織由来サイトカイン(アディポサイトカイン)の心血管系における役割
・心臓リモデリングと細胞外マトリックス分解産物との関連に関する研究
・生理活性因子・薬物の心・血管反応性とイオンチャネル電流に及ぼす影響
トピックス (受賞歴)
第155回日本獣医学会学術集会 優秀ポスター賞
第153回日本獣医学会学術集会 獣医学奨励賞
第151回日本獣医学会学術集会 大会長賞
第148回日本獣医学会学術集会 比較薬理毒性学会奨励賞
第147回日本獣医学会学術集会 優秀ポスター賞
第145回日本獣医学会学術集会 ベストプレゼンテーション賞
研究業績 (2015)

1. 風間恭輔、岡田宗善、山脇英之. (総説) 新規アディポサイトカインomentinは肥満症による高血圧症治療の新たな標的となり得るか?日薬理誌(印刷中)2015

2. Usui T, Nijima R, Sakatsume T, Otani K, Kameshima S, Okada M, and Yamawaki H. Eukaryotic elongation factor2 kinase controls proliferation and migration of vascular smooth muscle cells. Acta Physiol (Oxf). In Press.

(2014)

1. Kazama K, Okada M, and Yamawaki H. A novel adipocytokine, omentin, inhibits monocrotaline-induced pulmonary arterial hypertension in rats. Biochem Biophys Res Commun. 452: 142-146, 2014

2. Usui T, Sakatsume T, Nijima R, Otani K, Kazama K, Morita T, Kameshima S, Okada M, and Yamawaki H. Death-associated protein kinase3 mediates vascular structural remodeling via stimulating smooth muscle cell proliferation and migration. Clin Sci (Lond). 127: 539-548, 2014

3. Morita T, Okada M, and Yamawaki H. Mechanisms underlying a decrease in KCl-induced contraction after long-term serum-free organ culture of rat isolated mesenteric artery. J Vet Med Sci. 76: 963-969, 201

4. Kazama K, Okada M, and Yamawaki H. A novel adipocytokine, omentin, inhibits platelet-derived growth factor-BB-induced vascular smooth muscle cell migration through anti-oxidative mechanism. Am J Physiol-Heart and Circulatory Physiology. 306: H1714-H1719, 20

5. Usui T, Naruo A, Okada M, Hayabe Y, and Yamawaki H. Brain-derived neurotrophic factor promotes angiogenic tube formation through generation of oxidative stress in human vascular endothelial cells. Acta Physiol (Oxf) 211: 385-394, 2014. With Editorial commentary.

6. Usui T, Okada M, and Yamawaki H. (Review) Zipper interacting protein kinase (ZIPK): function and signaling. Apoptosis 19: 387-391, 2014.

7. Usui T, Morita T, Okada M, and Yamawaki H. Histone deacetylase 4 controls neointimal hyperplasia via stimulating proliferation and migration of vascular smooth muscle cells. Hypertension 63: 397-403, 20

(2013)

1. Okada M, Suzuki A, Yamawaki H, and Hara Y. Levosimendan inhibits interleukin-1b-induced cell migration and MMP-9 secretion in rat cardiac fibroblasts. Eur J Pharmacol 718: 332-339, 2013.

2. Phalitakul S, Okada M, Hara Y, and Yamawaki H. Vaspin prevents methylglyoxal-induced apoptosis in human vascular endothelial cells by inhibiting reactive oxygen species generation. Acta Physiol (Oxf) 209: 212-219, 2013. With Editorial commentary.

3. Usui T, Okada M, Hara Y, and Yamawaki H. Eukaryotic elongation factor 2 kinase regulates the development of hypertension through oxidative stress-dependent vascular inflammation. Am J Physiol-Heart and Circulatory Physiology 305: H756-H768, 2013.

4. Kazama K, Okada M, Hara Y, and Yamawaki H. A novel adipocytokine, omentin, inhibits agonists-induced increases of blood pressure in rats. J Vet Med Sci 75: 1029-1034, 2013.

5. Okada M, Watanabe S, Matada T, Asao Y, Hamatani R, Yamawaki H, and Hara Y. Inhibitory Effects of Psychotropic Drugs on the Acetylcholine Receptor-Operated Potassium Current (IK.ACh) in Guinea-pig Atrial Myocytes. J Vet Med Sci 75:743-747.

6. 臼井達哉、岡田宗善、原幸男、山脇英之. (総説)高血圧症の病態を制御する新たなカルモジュリン関連蛋白質の血管系における機能. 日薬理誌 141:85-89, 2013.

7. Okada M, Noma C, Yamawaki H, and Hara Y. Negative inotropic effect of carbachol and interaction between acetylcholine receptor-operated potassium channel (K.ACh channel) and GTP binding protein in mouse isolated atrium- a novel methodological trial. J Vet Med Sci 75:377-380, 2013.

8. Mukohda M, Morita T, Okada M, Hara Y, and Yamawaki H. Long-term methylglyoxal treatment causes endothelial dysfunction of rat isolated mesenteric artery. J Vet Med Sci 75:151-157, 2013.

9. Morita T, Okada M, Hara Y, and Yamawaki H. Addition of adult serum improves endothelium-dependent relaxation of organ-cultured rat mesenteric artery via inhibiting mitochondrial reactive oxygen species. Vascul Pharmacol 58:105-111, 2013.

(2012)

1. Mukohda M, Okada M, Hara Y, and Yamawaki H. Methylglyoxal accumulation in arterial walls causes vascular contractile dysfunction in SHR. J Pharmacol Sci 120:26-35, 2012.

2. Usui T, Okada M, Hara Y, and Yamawaki H. DAPK3 mediates vascular inflammation and development of hypertension in

spontaneously hypertensive rats. Hypertension 60:1031-1039, 2012.

3. Phalitakul S, Okada M, Hara Y, and Yamawaki H. A novel adipocytokine, vaspin inhibits platelet-derived growth factor-BB-induced migration of vascular smooth muscle cells. Biochem Biophys Res Commun 423:844-849, 2012.

4.Yamawaki H, Kameshima S, Usui T, Okada M, and Hara Y. A novel adipocytokine, chemerin exerts anti-inflammatory roles in human vascular endothelial cells. Biochem Biophys Res Commun 423:152-157, 2012.

5. Okada M, Mizuno W, Nakarai R, Matada T, Yamawaki H, and Hara Y. Benzodiazepines inhibit the acetylcholine receptor-operated potassium current (IK.ACh) by different mechanisms in guinea-pig atrial myocytes. J Vet Med Sci 74:879-884, 2012.

6.Kazama K, Usui T, Okada M, Hara Y, and Yamawaki H. Omentin plays an anti-inflammatory role through inhibition of TNF-a-induced superoxide production in vascular smooth muscle cells. Eur J Pharmacol 686:116-123, 2012.

7. Usui T, Okada M, Mizuno W, Oda M, Ide N, Morita T, Hara Y, and Yamawaki H. HDAC4 mediates development of hypertension via vascular inflammation in spontaneous hypertensive rats. Am J Physiol-Heart and Circulatory Physiology 302:H1894-H1904, 2012.

8. Mukohda M, Okada M, Hara Y, and Yamawaki H .(Review) Exploring mechanisms of diabetes-related macrovascular complications: role of methylglyoxal, a metabolite of glucose on regulation of vascular contractility. J Pharmacol Sci 118:303-310, 2012.

9. Yamawaki H, Takahashi M, Mukohda M, Morita T, Okada M, and Hara Y. A novel adipocytokine, nesfatin-1 modulates peripheral arterial contractility and blood pressure in rats. Biochem Biophys Res Commun 418:676-681, 2012.

10. Mukohda M, Morita T, Okada M, Hara Y, and Yamawaki H. Long-term methylglyoxal treatment impairs smooth muscle contractility in organ-cultured rat mesenteric artery. Pharmacol Res 65:91-99, 2012.

(2011)

1. Morita T, Okada M, Hara Y, and Yamawaki H. Mechanisms underlying impairment of endothelium-dependent relaxation by fetal bovine serum in organ-cultured rat mesenteric artery. Eur J Pharmacol 668:401-406, 2011.

2. Phalitakul S, Okada M, Hara Y, and Yamawaki H. Vaspin prevents TNF-a-induced intracellular adhesion molecule-1 via inhibiting reactive oxygen species-dependent NF-kB and PKCq activation in cultured rat vascular smooth muscle cells. Pharmacol Res 64:493-500, 2011.

3. Yamawaki H. (Review) Vascular effects of novel adipocytokines: focus on vascular contractility and inflammatory responses. Biol Pharma Bull 34:307-310, 2011.

4. Yamawaki H. (Review) Mechanisms of action of novel adipocytokines on the vascular system. Nihon Yakurigaku Zasshi 137: 131-135, 2011.

5. Yamawaki H, Kuramoto J, Kameshima S, Usui T, Okada M, and Hara Y. Omentin, a novel adipocytokine inhibits TNF-induced vascular inflammation in human endothelial cells. Biochem Biophys Res Commun 408:339-343, 2011.

7. Usui T, Okada M, Hara Y, and Yamawaki H. Exploring calmodulin-related proteins, which mediate development of hypertension, in vascular tissues of spontaneous hypertensive rats. Biochem Biophys Res Commun 405:47-51, 2011.

(2010)

1. Yamawaki H, Tsubaki N, Mukohda M, Okada M, and Hara Y. Omentin, a novel adipokine, induces vasodilation in rat isolated blood vessels. Biochem Biophys Res Commun. 393:668-672, 2010.

2. Mukohda M, Yamawaki H, Okada M, and Hara Y. Methylglyoxal augments angiotensin II-induced contraction in rat isolated carotid artery. J Pharmacol Sci 114:390-398, 2010.

3. Mukohda M, Yamawaki H, Okada M, and Hara Y. Methylglyoxal enhances sodium nitroprusside-induced relaxation in rat aorta. J Pharmacol Sci 112:176-183, 2010.

4. Mukohda M, Ueno S, Kamibayashi M, Okada M, Yamawaki H, and Hara Y. Influences of organic solvents on CYPMPO-electron spin resonance spectra in in vitro radical generating systems. J Vet Med Sci 72:1547-50, 2010.

5. Morita T, Yamawaki H, Okada M, and Hara Y. Contractile characteristics of rat mesenteric artery after organ culture. J Vet Med Sci 72:1621-7, 2010.

6. Usui T, Yamawaki H, Kamibayashi M, Okada M, and Hara Y. Mechanisms underlying a Ca2+/calmodulin antagonist, CV-159-mediated anti-inflammatory effects in cultured vascular smooth muscle cells. J Pharmacol Sci 113:214-223, 2010.

7. Usui T, Yamawaki H, Kamibayashi M, Okada M, and Hara Y. CV-159, a unique dihydropyridine derivative, prevents TNF-induced inflammatory responses in human umbilical vein endothelial cells. J Pharmacol Sci 113:182-191, 2010.

8. Okada M, Yamawaki H, and Hara Y. Angiotensin II enhances interleukin-1beta-induced MMP-9 secretion in adult rat cardiac fibroblasts. J Vet Med Sci 72:735-739, 2010.

9. Okada M, Kosaka N, Hoshino Y, Yamawaki H, and Hara Y. Effects of captopril and telmisartan on Matrix metalloproteinase-2 and -9 expressions and development of left ventricular fibrosis induced by isoprenaline in rats. Biol Pharma Bull 33:1517-1521, 2010.

(2009)

1. Hara Y, Ike A, Tanida R, Okada M, and Yamawaki H. Involvement of cyclooxygenase-2 in carbachol-induced positive inotropic response in mouse isolated left atrium. J Pharmacol Exp Ther 331:808-815, 2009.

2. Okada M, Harada T, Kikuzuki R, Yamawaki H, and Hara Y. Effects of telmisartan on right ventricular remodeling induced by monocrotaline in rats. J Pharmacol Sci 111:193-200, 2009.

3. Fu B-D, Yamawaki H, Okada M, and Hara Y. Vaspin can not inhibit TNF-a-induced inflammation of human umbilical vein endothelial cells. J Vet Med Sci 71:1201-1207, 2009.

4. Yamawaki H, Hara N, Okada M, and Hara Y. Visfatin causes endothelium-dependent relaxation in isolated blood vessels. Biochem Biophys Res Commun 383:503-508, 2009.

5. Mukohda M, Yamawaki H, Nomura H, Okada M, and Hara Y. Methylglyoxal inhibits smooth muscle contraction in isolated blood vessels. J Pharmacol Sci 109:305-310, 2009.

(2008)

1. Yamawaki H, Saito K, Okada M, and Hara Y. Methylglyoxal mediates vascular inflammation via JNK and p38 in human endothelial cells. Am J Physiol Cell Physiol 295:C1510-C1517, 2008.

2. Okada M, Kikuzuki R, Harada T, Hori Y, Yamawaki H, and Hara Y. Captopril attenuates matrix metalloproteinase-2 and -9 in monocrotaline-induced right ventricular hypertrophy in rats. J Pharmacol Sci 108:487-494, 2008.

3. Nomura H, Yamawaki H, Mukohda M, Okada M, and Hara Y. Mechanisms underlying pioglitazone-mediated relaxation in isolated blood vessel. J Pharmacol Sci 108:258-265, 2008.

4. Baden T, Yamawaki H, Saito K, Mukohda M, Okada M, and Hara Y. Telmisartan inhibits methylglyoxal-mediated cell death in human vascular endothelium. Biochem Biophys Res Commun 373:253-257, 2008.

5. Yamawaki H, and Hara Y. Glyoxal causes inflammatory injury in human vascular endothelial cells. Biochem Biophys Res Commun 369:1155-1159, 2008.

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