Grant-in-Aid for General Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||Kitasato University|
KATORI Makoto Kitasato Univ.Sch.of Med.Professor., 医学部, 教授 (50050365)
OHNO Takashi Kitasato Univ.Sch.of Med.Instructer, 医学部, 助手 (60185345)
HATANAKA Ko Kitasato Univ.Sch.of Med.Instructer, 医学部, 助手 (00228470)
KAWAMURA Michiko Kitasato Univ.Sch.of Med.Instructer, 医学部, 助手 (00154104)
MAJIMA Masataka Kitasato Univ.Sch.of Med.Lecturer, 医学部, 講師 (70181641)
HARADA Yoshiteru Kitasato Univ.Sch.of Med.Prof., 医学部, 教授 (20050677)
|Project Period (FY)
1993 – 1995
Completed(Fiscal Year 1995)
|Budget Amount *help
¥7,500,000 (Direct Cost : ¥7,500,000)
Fiscal Year 1995 : ¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1994 : ¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1993 : ¥3,100,000 (Direct Cost : ¥3,100,000)
|Keywords||renal kallikrein / kininogen / kininase / carboxypeptidase Y / Brown Norway rats / DOCA-salt hypertension / spontaneously hypertensive rats / ebelactone B / DOCA-食塩高血圧 / キニノゲン欠損ラット / 実験的高血圧 / 尿キニナーゼ阻害薬 / neutral endopeptidase / carboxypeptidase Y / oxytocin / ナトリウム利尿 / 尿カリクレイン / アンギオテンシンII / 食塩による高血圧発症 / アルドステロン / スピロノラクトン / ポストスタチン|
The present works, using kininogen-deficient rats (Brown Norway-Katholiek (BN-Ka) rats), revealed that renal kallikrein act as a flood gate for excess sodium or sodium retention in the body and the reduced excretion of renal kallikrein plays a critical role in the early stage of the development of hypertension.
I.A role of renal kallikrein-kinin system for sodium excretion
1. Comparing with normal BN-Kitasato (Ki) rats, deficient BN-Ka rats were sensitive to NaCl and 2% NaCl in diet developed hypertension, by excretion of less urine volume and urinary sodium than normal BN-Kr rats.
2. A non-pressor dose of angiotensin II to deficient BN-Ka rats developed hypertension by accumulating sodium in cells through aldosterone release.
3. Kinin generated showed natriuresis through B_2 receptor localized on the luminal side of the tubular cells, as shown by increased natriuresis by ebelactone B,which selectively inhibited carboxypeptidase Y-like exopeptidase in urine.
II.A role of renal kallikrein-kinin system in the development of hypertension
1. Spontaneously hypertensive rats (SHR) excrete less urinary kallikrein during the development of hypertension than Wistar Kyoto rats (WKY).
2. Oxytocin induced natriuresis in anesthetized rats and excreted renal kallikrein. The kallikrein level in kidney of SHR was not different from that in WKY,but the kallikrein excretion by oxytocin were much lower, suggesting that SHR showed difficulty in secretion of renal kallikrein.
3. The blood pressure reached a plateau in DOCA-salt hypertension of uninephrectomized deficient BN-Ka rats 2 weeks after the onset of the treatment.
4. Renal kallikrein releasers, such as oxytocin, and urine kininase inhibitors, such as ebelactone B,may be novel anti-hypertensive drugs.