| Project/Area Number |
09671182
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The Jikei University School of Medicine |
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Principal Investigator |
SUZUKI Hiroaki JIKEI UNIVERSITY DEPARTMENT OF MEDICINE 4, 医学部, 助手 (60175411)
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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 |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | cardiac hypertrophy / renal failure / lysosomal proteinase / ACE inhibitor / calcium antagonist / proteinase / cathepsin / enalapril / verapamil / 尿毒症 / プロテアーゼ / 心肥大 / レニン / H9C2 |
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| Research Abstract |
The pathogenesis of cardiac hypertrophy in chronic uremia is poorly understood. In the present study, the long-term effects of chronic uremia on cardiac morphology and various cysteine proteinase of the heart were investigated in rats with and without antihypertensive therapy by the angiotensin, converting enzyme inhibitor enalapril or by the calcium channel blocker veramapil. Sixteen weeks after subtotal nephrectomy considerable uremia had developed associated with arterial hypertension, rise in heart weight and heart weight/bodyweight ratio. Morphologically myocardial cells developed marked hypertrophy. Determination of various cysteine proteinase by fluorometry revealed a significant decline of cathepsin B activity while the activities of cathepsin H and L were unchanged. Antihypertensive treatment with enalapril and verapamil normalized the blood pressure and improved renal function significantly. Myocardial cell hypertrophy and the enhanced heart weight/body weight ratio were normalized under treatment with enalapril but not with verapamil. Simultaneously, the impaired cathepsin B activity returned to the normal range after enalapril treatment. It is concluded that the cardiac hypertrophy in uremia is at least partly caused by an activation of the circulating and/or cardiac renin-angiotensin system. Impaired proteinase activity in the uremia state may be improved in the development of cardiac hypertrophy.
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