| Project/Area Number |
09470527
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | OSAKA CITY UNIVERSITY MEDICAL SCHOOL |
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Principal Investigator |
IWAO Hiroshi OSAKA CITY UNIVERSITY MEDICAL SCHOOL, PHARMACOLOGY, PROFESSOR, 医学部, 教授 (00137192)
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| Co-Investigator(Kenkyū-buntansha) |
MITSUYAMA Shokei OSAKA CITY UNIVERSITY MEDICAL SCHOOL, PHARMACOLOGY, ASSISTANT PROFESSOR, 医学部, 講師 (10195414)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | RENIN-ANGIOTENSIN SYSTEM / SIGNAL TRANSDUCTION / ORGA DAMAGE / MAP KINASE / CARDLAC HYPERTROPHY / ANGIOTENSIN RECEPTOR ANTAGONIST / CONVERTING ENZYME INHIBITOR / 心肥大 |
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| Research Abstract |
The renin-angiotensin-aldosterone system (RAAS) plays an important role in both the physiological regulation of blood pressure and in the pathophysiological disruption of cardiovascular organ damages. Angiotensin II (Ang II) is the primary biological mediator of the RAAS. Pathophysiological actions of Ang II is mediated by the angiotensin II type I receptor, for examples of vasoconstriction on vascular smooth muscle, secretion of aldosterone, reabsorption of sodium in the renal proximal nephron, and cell growth and proliferation.
Treatments of RAAS inhibitors, angiotensin converting enzyme and Ang II type I receptor antagonist, in hypertensive rat models caused prevention effects of hypertension, cardiac hypertrophy, and vascular sclerosis and glomerular sclerosis. In addition, these effects were associated with suppressive gene expressions of TGF-b, collagen type I, collagen type II, fibronectin. These gene expression were caused by the stimulation of Ang II type I receptor through the activation of mitogen-activated protein kinases (ERK and JNK). Both angiotensin converting enzyme and Ang II type I receptor antagonist inhibited the activation of ERK and JNK.
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