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Is angiotensin II involved in dehydration-enhanced fever induced by endotoxin in rats ?

血管紧张素II是否与内毒素引起的大鼠脱水增强发热有关？

基本信息

批准号：
12670060
负责人：
MIYOSHI Michio
金额：
$ 2.37万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670060/
关键词：
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

项目摘要

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.

据报道，与正常水分条件相比，宿主在脱水条件下会出现明显的发烧。本研究旨在探讨血管紧张素II(Ang II)是否参与了内毒素(LPS)诱导的脱水大鼠发热的增强作用。结果表明，静脉注射内毒素引起的脱水大鼠的发热明显高于正常水合的大鼠。在脱水条件下，血管紧张素转换酶(ACE)抑制剂可显著抑制内毒素诱导的发热。从以上结果来看，Ang II很可能参与了在脱水条件下内毒素诱导的促炎细胞因子的产生。为了验证这种可能性，我们接下来检测了血管紧张素转换酶抑制剂和1型血管紧张素Ⅱ受体拮抗剂(AT_1受体)对内毒素诱导的脱水大鼠产生促炎细胞因子IL-1和IL-6的影响。注射脂多糖可诱导大鼠肝脏IL-1ACE基因表达显著增加，这种作用可被β抑制剂预处理显著减弱。血管紧张素转换酶抑制剂可降低内毒素诱导的肝组织IL-1β蛋白浓度的升高。内毒素诱导前给予AT1受体拮抗剂后，肝组织中IL-1β浓度升高的幅度明显降低。此外，血管紧张素转换酶抑制剂可降低内毒素引起的血浆IL-6浓度升高。这些结果表明，Ang II及其AT1受体在内毒素诱导的致炎细胞因子的产生中起重要作用，而增强脱水大鼠的内毒素发热是由于Ang II分泌增加，从而刺激细胞因子的产生。