| Project/Area Number |
02670406
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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 | Wakayama Medical College |
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Principal Investigator |
HANO Takuzo Wakayama Medical College Department of Medicine Assistant Professor, 医学部, 講師 (90156381)
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| Co-Investigator(Kenkyū-buntansha) |
HISHIO Ichiro Wakayama Medical College Department of Medicine Professor, 医学部, 教授 (40089165)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Spontaneously Hypertensive Rat / DOCA-salt Hypertension / Dahl Rat / Renal Reduced Mass Hypertension / Na, K-ATPase Inhibitor / Uptake 1 / Mesenteric Artery / Synaptosome / ノルエピネフリン / 再摂取 / digαin / ouabain / 交感神経 / ジギタリス様物質 / 部分賢摘食塩ラット |
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| Research Abstract |
Norepinephrine (NE) uptake in sympathetic nerve terminals plays an important role to regulate the concentration of NE in the sympathetic nerve cleft. In the present study, we examined the NE uptake and NE overflow in the several experimental hypertension models in rats.
Young spontaneously hypertensive rats (SHR) showed the increased NE uptake and overflow from the sympathetic nerve terminals in mesenteric arterial preparation. In contrast, NE uptake and overflow were reduced in adult SHR. NE overflow was increased but NE uptake was reduced in Dahl-salt sensitive rats. In DOCA-salt hypertensive rats, NE uptake was reduced. These results suggested that NE uptake is changed by aging and play an important role in the development of hypertension in salt-dependent hypertension. NE overflow and NE uptake in synaptosomal fraction were increased in young spontaneously hypertensive rats and were reduced in adult rats. Sympathetic function in the central nervous system showed a similar trend as that in peripheral sympathetic nervous system.
It has been reported that humoral factors can effect the NE uptake in the sympathetic nerve terminals. In the present study, we partially purifies Na, K^+-ATPase inhibitor from the urine of reduced renal mass hypertension and examine the effects of indigenous Na, K^+-ATPase inhibitor on NE uptake in synaptosomal fraction of hypothalamus in rats. Urine of reduced renal mass hypertension was collected and endogenous Na, K-ATPase inhibitor was separated by gel- filtration and reversed HPLC which showed digoxine-like immunoreactivity. The polarity of this substance was similar to digoxine and its molecular weight was about 400. Partially purified Na, K+-ATPase inhibitor suplressed the NE uptake in the synaptosomal fraction in dose-dependent manner in rats. These results showed that endogenous Na, K^+-ATPase inhibitor has a similar chemical characters as digoxine and a inhibitory action on NE uptake in the peripheral nerve endings.
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