GENERATION OF TRANSGENIC MICE WITH ELEVATED BLOOD-PRESSURE BY INTRODUCTION OF THE RAT RENIN AND ANGIOTENSINOGEN GENES

被引:140
作者
OHKUBO, H
KAWAKAMI, H
KAKEHI, Y
TAKUMI, T
ARAI, H
YOKOTA, Y
IWAI, M
TANABE, Y
MASU, M
HATA, J
IWAO, H
OKAMOTO, H
YOKOYAMA, M
NOMURA, T
KATSUKI, M
NAKANISHI, S
机构
[1] CENT INST EXPTL ANIM,KAWASAKI 213,JAPAN
[2] NATL CHILDRENS MED RES CTR,DEPT PATHOL,TOKYO 154,JAPAN
[3] KAGAWA MED SCH,DEPT PHARMACOL,KAGAWA 76107,JAPAN
[4] TOKAI UNIV,SCH MED,DEPT DNA BIOL,ISEHARA,KANAGAWA 25911,JAPAN
[5] KOBE GAKUIN UNIV,FAC PHARMACEUT SCI,DEPT PHARMACOL,KOBE 673,JAPAN
关键词
Animal model; Captopril; Hypertension/; Renin-angiotensin system;
D O I
10.1073/pnas.87.13.5153
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The role of the renin-angiotensin system in blood pressure control and in the development of hypertension was investigated by generating transgenic mice carrying the rat rain or angiotensinogen gene or both genes under the control of the mouse metallothionein I promoter. The systolic blood pressure was significantly elevated in transgenic mice carrying both transgenes but was maintained normally in those bearing either of the transgenes. The transgene was effectively and properly transcribed to form the mature mRNA in the transgenic mice. The production of rat renin and angiotensinogen in the transgenic mice carrying the corresponding transgene was also verified by immunoanalyses of these proteins. Further-more, the specific angiotensin-converting enzyme inhibitor captopril was effective in reducing the elevated blood pressure of the hypertensive transgenic mice. These results indicate that the combined action of the exogenous rat renin and angioten-sinogen is responsible and necessary for elevation of blood pressure in the hypertensive transgenic mice.
引用
收藏
页码:5153 / 5157
页数:5
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