Effect of endogenous NOS inhibitor on pulmonary arterial pressure

Research Project

Project/Area Number	25462447
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Anesthesiology
Research Institution	Yokohama City University
Principal Investigator	Shinbori Nobuhiro 横浜市立大学, 医学研究科, 客員准教授 (60404993)
Co-Investigator(Kenkyū-buntansha)	渡辺至横浜市立大学, 医学研究科, 客員教授 (20534142) 水野祐介横浜市立大学, 附属病院, 准教授 (80433192) 川上裕理地方独立行政法人神奈川県立病院機構神奈川県立こども医療センター(臨床研究所), 臨床研究所, 医長 (90407958)
Project Period (FY)	2013-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000) Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	肺高血圧 / 一酸化窒素 / 内皮細胞 / 一酸化窒素合成酵素 / arginase / ADMA / DDAH / 一酸化窒素合成酵素阻害物質 / ＡＤＡＭ / 内因性NOS阻害物質 / ＤＤＡＨ１ / ＰＲＭＴ２
Outline of Final Research Achievements	Impairment of endogenous release of nitric oxide (NO), which causes vascular vasodilation and inhibition of smooth muscle cell proliferation, is well known to play a critical role in developing pulmonary hypertension (PH).　We explored the mechanism of impared ehdothelial function and eNOS activity in PH using monocrotaline-induced PH rats. Increase in PRMT2 and decrease in DDAH1 and DDAH2 in the PH model were associated with increased ADMA contents and consequent impairment of NOS activity. These results may be potentially useful to lower ADMA level for therapeutic benefit.