Journal
JOURNAL OF PHYSIOLOGICAL SCIENCES
Volume 69, Issue 4, Pages 581-587Publisher
SPRINGER JAPAN KK
DOI: 10.1007/s12576-019-00679-4
Keywords
Hypertension; Renin; Angiotensinogen; Renin-angiotensin system; Transgenic mice; Knockout mice
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Funding
- Ministry of Education, Science, Sports, and Technology of Japan
- Japan Society for the Promotion of Science
- Ministry of Health, Labour, and Welfare of Japan
- Chichibu Cement Co. Ltd.
- Iwaki Foundation
- Naito Memorial Foundation
- Ciba-Geigy Foundation
- Fumi Yamamura Memorial Foundation for Female Natural Scientists
- Kanae Foundation of Research for New Medicine
- Circulation Biosystems at the University of Tsukuba
- Uehara Memorial Foundation
- Inamori Foundation
- Asahi Glass Foundation
- Naito Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Nissan Science Foundation
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Hypertension is one of the most important risk factors and a leading cause of death from cardiovascular and cerebrovascular diseases. Based on numerous previous studies, hypertension is thought to be caused by the complex mutual interactions of genetic factors and environmental factors, such as excessive salt intake and stress. However, its detailed mechanisms are not yet clearly understood. The renin-angiotensin system (RAS) is a key hormonal system in the pathogenesis of hypertension. New knowledge is still accruing on this cascade, even after more than 120 years since the discovery of renin. To clarify the molecular mechanisms of RAS in vivo, we created transgenic mice with chronic hypertension. These mice carry the human genes encoding renin, a hypertensive enzyme, and its substrate angiotensinogen. Hypotensive mice homozygous for a targeted disruption of the angiotensinogen gene were also created. This review presents our 47-year history of RAS research.
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