Hypertensive rats produced by in vivo introduction of the human renin gene.

Hypertensive rats produced by in vivo introduction of the human renin gene.
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通过体内导入人肾素基因产生的高血压大鼠。

DOI:
10.1161/01.res.73.5.898
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发表时间:
1993
影响因子:
20.1
通讯作者:
T. Ogihara
T. Ogihara
中科院分区:
医学1区
文献类型:
--
作者:
N. Tomita;J. Higaki;Y. Kaneda;H. Yu;R. Morishita;H. Mikami;T. Ogihara

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建立了一种高效、无毒的仙台病毒(日本血凝病毒[HVJ])、脂质体和核蛋白介导的体内基因转移方法。本研究利用HVJ和脂质体(HVJ-liposomes, HVJ-liposomes)高效体内基因转移法,将人肾素基因导入成年大鼠肝脏,制备人肾素依赖性高血压模型大鼠。与注射不含人肾素基因的hvj -脂质体的对照大鼠相比,注射含人肾素基因的hvj -脂质体的大鼠血压在6天内显著升高。移植后第5天,转染人肾素基因的大鼠血浆中出现人活性肾素和血管紧张素II。此外,这些大鼠的血压与血浆中人类活性肾素和血管紧张素II的水平显著相关。为了证实血压升高是由人肾素基因的表达引起的,我们使用了一种新开发的特异性人肾素抑制剂fk906。通过静脉注射这种药物,升高的血压恢复正常。这些数据表明,这种高血压大鼠是由人肾素基因在体内转移到大鼠肝脏而产生的,并且表达的人肾素分裂了大鼠底物(血管紧张素原)。通过体内基因转移制备的高血压大鼠,为进一步的高血压研究提供了有益的依据。
We established an efficient and nontoxic in vivo gene transfer method mediated by the Sendai virus (hemagglutinating virus of Japan [HVJ]), liposomes, and nuclear protein. In this study, to produce a hypertensive model rat that is dependent on human renin, the human renin gene was introduced into adult rat liver by our efficient in vivo gene transfer method using HVJ and liposomes (HVJ-liposomes). The rats treated with HVJ-liposomes containing the human renin gene showed a significant elevation of blood pressure for 6 days compared with control rats, which received injections of HVJ-liposomes without the human renin gene. On day 5 after the transfer, human active renin as well as angiotensin II were found in the plasma of rats in which the human renin gene was introduced. Moreover, the blood pressure of these rats was significantly correlated with the plasma levels of human active renin and angiotensin II. To confirm that the elevated blood pressure was due to the expression of the human renin gene, we administered a newly developed specific human renin inhibitor, FK 906. The elevated blood pressure was normalized by the intravenous administration of this drug. These data indicate that this hypertensive rat was produced by the in vivo transfer of the human renin gene into rat liver and that the expressed human renin cleaved rat substrate (angiotensinogen). This hypertensive rat produced by in vivo gene transfer should be useful in further studies on hypertension.
DOI: 10.1093/ajh/5.8.495
发表时间: 1992
影响因子: 3.2
作者:
Gahnem,F;Sealey,JE;Atlas,SA;Laragh,JH
通讯作者: Laragh,JH
使用电穿孔将生物活性外源基因引入原代大鼠肝细胞。
DOI: 10.1128/mcb.6.2.716-718.1986
发表时间: 1986
影响因子: 5.3
作者:
Tur-Kaspa,R;Teicher,L;Levine,BJ;Skoultchi,AI;Shafritz,DA
通讯作者: Shafritz,DA
磷酸化酶激酶、蛋白激酶 C 和其他 Ca2 敏感蛋白激酶在肝细胞对血管紧张素 II 和加压素反应中作用的证据。
DOI: --
发表时间: 1984
期刊: The Journal of biological chemistry
影响因子: --
作者:
Garrison,JC;Johnsen,DE;Campanile,CP
通讯作者: Campanile,CP