1992 Fiscal Year Final Research Report Summary
Pharmacological application of transgenic animals
| Project/Area Number |
03044107
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Kagawa Medical School |
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Principal Investigator |
KIMURA Shouji Kagawa Medical School, 医学部, 助手
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| Co-Investigator(Kenkyū-buntansha) |
DETLEV Gante The MaxーDelbruckーCentrum fur Molekulare, 研究所長
KIM Shoukei Osaka City University Medical School, 医学部, 助手 (10195414)
IWAO Hiroshi Osaka City University Medical School, 医学部, 教授 (00137192)
GANTEN Detlev The Max-Delbruck-Centrum fur Molekulare Medizine
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| Project Period (FY) |
1991 – 1992
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| Keywords | Hypertension / Transgenic rat / Renin-angiotensin-system |
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| Research Abstract |
Transgenic rats (TGR (mRen2)27) harboring the mouse Ren-2 renin gene have been recently generated as a model for the study of primary hypertension. Using this model animal, mechanism of the initiation of hypertension, organ disorder of hypertensive status and hypertensive drug evaluation were investigated. The organ distribution of transfected mouse renin gene was expressed in the adrenal gland followed by thymus, gastrointestinal tract, genital tract, kidney, brain, and lung. No expression was detected in the liver and submandibular gland. The blood pressure was increased rapidly from 4 to 8 weeks old and maintained in 200 mmHg in systolic pressure. The development of high blood pressure in homozygous rats was accelerated compared with that of heterozygous rats. Plasma renin and angiotensin II were low, and renal renin gene expression was quit low in this rats. Treatments of both Captopril (converting enzyme inhibitor, 1 or 10mg/Kg) and Dup753 (angiotensin II receptor antagonist, 10mg/Kg) were decreased blood pressure to normal level. Sodium depletion also normalized blood pressure. Ren-2 gene expressed in mesenteric and aortic tissue, and release of angiotensin II from isolated perfused hindquarters was increased in this rats. Organ disorder of this rats were observed in the large vessels, kidney (glomerular lesion and sclerosis of arterioles), and heart. These findings strongly suggested that rats is a useful model for hypertension research and therapeutic intervention of new drugs.
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