The role of kinin-tensin system in the cardiovascular system
| Project/Area Number |
05454279
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Fukuoka University |
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Principal Investigator |
ARAKAWA Kikuo Fukuoka University School of Medicine, Professor, 医学部, 教授 (90078783)
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| Co-Investigator(Kenkyū-buntansha) |
KINOSHITA Akio Fukuoka University School of Medicine, Lecturer, 医学部, 講師 (40258546)
SASAGURI Manabu Fukuoka University School of Medicine, Lecturer, 医学部, 講師 (00178675)
IDEISHI Munehito Fukuoka University School of Medicine, Associate Professor, 医学部, 助教授 (20131807)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1995: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1993: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Kinin / Angiotensin / Serine protease / Chymase / Tryptase / PAI-1 / Coronary artery / Smooth muscle cell / 血管平滑筋細胞 / ヒト心臓キマーゼ |
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| Research Abstract |
We investigated the cardiovascular role of kinin-tensin system in which serine proteases produce vasodilator bradykinin and vasoconstrictor angiotensin II pH dependently.
1. (1) Exercise induced rise in plasma levels of angiotenisin II was partly inhibited by the administration of angiotenisn converting enzyme (ACE) inhibitor, captopril, and the rise was further inhibited by the coadministratio of captopril with a serine protease inhibitor, nafamostat. Thus, it was suggests that angiotensin II was produced by both ACE and an enzyme belongs to kinin-tens system during exercise.
(2) Human urinary kallikrein formed angiotensin II directly from homologous human angiotensinogen independent of renin or angiotensin converting enzyme.
2. Angiotensin II caused human aortic smooth muscle cell hypertrophy in culture.
Human aortic smooth muscle cell converted angiotensin I to II.
3. (1) Angiotensin converting activity was detectable in membrane fractions of human lung and left ventricle, and the activities were more sensitive to chymostatin thatn to captopril.
(2) Chymase mRNA was not detectable by PCR in cultured human aortic endothelial cells.
4. Tryptase-rich fractions of human lung and aortic tissue extracts showed angiotensin converting activity, and the activities were inhibited almost completely by chymostatin. Thus, tryptase is not a member of a serine protease family of the kinin-tensin system.
5. Angiotensin II increased PAI-1 mRNA in cultured human coronary artery smooth muscle cells and increased PAI-1 antigen and activity in the culture medium. The role of angiotensin II in the development of arteriosclerosis through the effects on coagulation/fibrinolysis is the future projects in our laboratory.
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Report
(4 results)
Research Products
(10 results)
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[Publications] Miura, S., Ideishi, M., Sakai, T., Motoyama, M., kinoshita, A.Sasaguri, M., Tanaka, H., Shindo, M., Arakawa, K.: "Angiotenisin II formation by an alternative pathway during exercise in humans." Journal of Hypertension. 12. 1177-1181 (1994)
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「研究成果報告書概要(欧文)」より
Related Report
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[Publications] Sasaguri, M., Ideishi, M., Ogata, S., Miura, S., Ikeda, M., Arakawa, K.: "Human urinary kallikrein can generate angiotensin II from homologous renin substrate." Hypertension Research Clinical and Experimental. 18. 33-37 (1995)
Description
「研究成果報告書概要(欧文)」より
Related Report
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