| Project/Area Number |
05670627
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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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 | Sapporo Medical University School of Medicine |
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Principal Investigator |
URA Nobuyuki Sapporo Med.Univ., School of Med., 医学部, 講師 (20185078)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Motoya Sapporo Med.Univ., School of Med., 医学部, 講師 (40207741)
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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 |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | atrial natriuretic peptide / renal kallikrein-kinin / neutral endopeptidase 24.11 / nitric oxide / hypertension / renal water-sodium metabolism / DOCA-salt rats / Dahl salt-sensitive rats / 高血圧 / Dah1食塩感受性高血圧ラット / 腎kinin / 心房性Na利尿ペプチド / 内皮由来血管弛緩因子 / neutral endopeptidase 24.11 / DOCA-saltラット / kidney / neutral endopeptidase 24.II / kinin / atrial natriuretic peptide / nitric oxide |
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| Research Abstract |
The activity of the renal kallikrein-kinin system is controlled by the concentration of intrarenal kinins. Neutral endopeptidase 24.11 (NEP) cleaves kinins as effectively as kininase I and kininase II.It is also well known that NEP metabolizes atrial natriuretic peptide (ANP). The present study evaluated the effects of NEP inhibitor on renal action by kininsANP and intric oxide in Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats, and on blood pressure in conscious Dahl salt-sensitive hypertensive rats. In normotensive rats, we demonstrated that (1) inhibition of NEP potenciates the contribution of kinins to the renal water-sodium metabolism and overcomes the contribution of ANP to that metabolism, (2) nitric oxide participates in the action of kinins, and (3) changes in urinary cGMP excretion do not reflect the canges in plasma ANP,but the changes in nitric oxide. On the other hand, it was also suggested that augumented ANP may contribute mainly to renal water-sodium handling by NEP inhibitor in DOCA-salt rats. In Dahl salt-sensitive rats, NEP inhibitor does not affect blood pressure. Therefore, the contributions of the two systems to the diuretic and natriuretic mechanisms of NEP inhibition may differ between Sprague-Dawley normotensiv rats and DOCA-salt hypertensive rats, and NEP inhibitor has no depressor effect at least in Dahl salt-sensitive hypertensive rats.
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