1994 Fiscal Year Final Research Report Summary
Molecular Research of the Etiology and Treatment of Hypertension
| Project/Area Number |
04404044
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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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 | Osaka University |
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Principal Investigator |
OGIHARA Toshio Osaka University, Medical School, Department of Geriatric Medicine, Associate Professor, 医学部, 教授 (60107042)
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| Co-Investigator(Kenkyū-buntansha) |
RAKUGI Hiromi Osaka University, Medical School, Department of Geriatric Medicine, Assistant Pr, 医学部, 助手 (20252679)
HIGAKI Jitsuo Osaka University, Medical School, Department of Geriatric Medicine, Assistant Pr, 医学部, 助手 (70189744)
MIKI Tetsuro Osaka University, Medical School, Department of Geriatric Medicine, Lecturer, 医学部, 講師 (00174003)
MIKAMI Hiroshi Osaka University, Medical School, Department of Geriatric Medicine, Associate Pr, 医学部, 助教授 (80173996)
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| Project Period (FY) |
1992 – 1994
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| Keywords | HYPERTENSION / GENE / MOLECULAR GENETICS / GENE DIAGNOSIS / GENE THERAPY / MOLECULAR BIOLOGY / GENE ANALYSIS / 遺伝子解析 |
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| Research Abstract |
To investigate the molecular etiology of hypertension, we have conducted genetic screening of the spontaneously hypertensive rat (SHR). We have detected so far two loci which are related with blood pressure determination : one is the NPY gene on chromosome 4 which induces blood pressure elevation, and the other is the PLCdelta _1 gene on chromosome 8 with hypotensive effect. We also showed that the angiotensin converting enzyme gene on chromosome 10 is related with salt-sensitivity of stroke-prone SHR,and that the mutation of adrenal P450_<11beta> gene may be responsible for the salt-resistance of Dahl's saltresistant rats. These results suggest that the mosaic of multiple genes contributes to the degermination of the blood pressure level.
On the other hand, in the human study using Japanese population, we confirmed significance of hypertensinogenic T235 variant of the angiotensinogen gene, which has been formerly reported in European Caucasians by Jeunemaitre et al. Although we failed
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to prove that the insertion/deletion polymorphism of angiotensin-converting enzyme associates with blood pressure in Japanese, we demonstrated that the deletion polymorphism of angiotensin converting enzyme gene could be a potent risk factor for not only myocardial infarction but also restenosis after percutaneous transluminal angioplasty in Japanese subjects.
Using an efficient and nontoxic in vivo gene transfer method (HVJ-liposome), we produced a hypertensive model rat that is dependent on human renin. The elevated blood pressure was normalized by the intravenous administration of specific human renin inhibitor. Next, HVJ-liposomes containing oligonucleotide complementary to rat angiotensinogen gene were injected into liver. The blood pressure of the rat treated with HVJ-liposome complexed with antisense oligomer decreased. These results showed that the HVJ-liposome could be potentially a good tool for the study of the renin-angiotensin system and a furture gene therapy for hypertension. Less
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