Is angiotensin II involved in dehydration-enhanced fever induced by endotoxin in rats ?
| Project/Area Number |
12670060
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | Tottori University |
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Principal Investigator |
MIYOSHI Michio Tottori University, Faculty of Medicine, Assistant, 医学部, 助手 (20093627)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Tatsuo Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (60182929)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Keywords | Angiotensin II / dehydration / angiotensin-converting enzyme inhibitor / Fever / interleukin-1β / interleukin-6 / mRNA / Angiotensin II type 1 receptor antagonist / ANG1型受容体拮抗薬 / インタ一ロイキン-1β / 内因性発熱物質 / ANG変換酵素阻害薬 / IL-1β |
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| Research Abstract |
It has been reported that a host develops a marked fever under dehydrated conditions compared with normally hydrated conditions. The present study was carried out to investigate whether angiotensin II (ANG II) is involved in the enhancement seen in dehydrated rats of the fever induced by lipopolysaccharide (LPS). The results showed that intravenous injection of LPS produced a fever in dehydrated rats that was significantly greater than that seen in normally hydrated rats. Under dehydrated conditions, the enhanced LPS-induced fever was significantly inhibited by the angiotensin-converting enzyme (ACE) inhibitor. From the above results, it seems highly likely that ANG II is involved in the LPS-induced production of proinflammatory cytokines under dehydrated conditions. To test this possibility, we next examined the effect of an ACE inhibitor and of an antagonist of the type 1 ANG II receptor (AT_1-receptor) on the LPS-induced production of the proinflammatory cytokines interleukin-1 (IL-1) and IL-6 in dehydrated rats. An injection of LPS induced a marked increase in the expression ofIL-1β mRNA in the liver, an effect that was significantly attenuated by pre-treatment with the ACE inhibitor. The ACE inhibitor reduced the LPS-induced increase in the hepatic concentration of IL-1β protein. When the AT_1-receptor antagonist was given before the LPS, the increase in the hepatic concentration of IL-1β was significantly reduced. Furthermore, the ACE inhibitor reduced the LPS-induced increase in the plasma concentration of IL-6. These results suggest that ANG II and its AT_1-receptor play an important role in the production of proinflammatory cytokines that is induced by LPS, and that the enhancement of the LPS-induced fever seen in dehydrated rats is due to increased secretion of ANG II which stimulates the production of the cytokines.
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Report
(3 results)
Research Products
(6 results)
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[Publications] Watanabe, T., Hashimoto, M., Wada, M., Imoto, T., Miyoshi, M., Sadamitsu, D. & Maekawa, T.: "Angiotensin-converting enzyme inhibitor inhibits dehydration-enhanced fever induced by endtoxin in rats"Am J Physiol Regulatory Integrative Comp Physiol. 279. R1512-R1516 (2000)
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