Inhibitory effect of arginase on pulmonary hypertension
| Project/Area Number |
16K10968
|
|---|
| 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 |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
古賀 資和 横浜市立大学, 医学部, 助教 (00637233)
水野 祐介 横浜市立大学, 附属病院, 准教授 (80433192)
|
|---|
| Project Period (FY) |
2016-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | arginase / 肺高血圧 / eNOS / arginine / 肺高血圧症 / 一酸化窒素 / 内皮細胞 / 内皮由来一酸化窒素合成酵素 / 一酸化窒素合成酵素 / 平滑筋 |
|---|
| Outline of Final Research Achievements |
Impairments of endothelial nitric oxide synthesis (eNOS) activity and nitric oxide (NO) are well known to play a critical role in developing pulmonary hypertension (PH).
In monocrolatine-induced rats, decreased eNOS activity and endothelium dependent relaxation (EDR) of PA ring were accompanied with increased arginase expression, which compete substrate with eNOS.Pretreatment of NOHA, arginase inhibitor, and arginine recovered EDR in PH rats.In PH rats, increased arginase expression and impaired availability of arginine could be associated with decreased EDR. Exploration of mechanism of arginase activity and arginine availability may be useful to develop novel treatment for PH.
|
| Academic Significance and Societal Importance of the Research Achievements |
肺高血圧症の併存は周術期の心血管合併症の発症率を有意に上昇させ、重症例では依然として管理は困難である。我々は肺高血圧ラットモデルを用い、肺高血圧症の原因の一つである肺血管内皮障害とそれに伴う一酸化窒素産生の低下を改善させる方法について、検討を行った。一酸化窒素合成酵素の活性低下の原因として、arginaseの発現亢進と一酸化窒素合成酵素の基質であるarginineの利用障害の可能性が示唆された。重症肺高血圧症の管理は依然困難であり、詳細な機序解明は新たな治療法の開発につながる可能性がある。
|
Report
(5 results)
Research Products
(1 results)
