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

据报道，与正常水合条件相比，宿主在脱水条件下会出现明显的发热。本研究旨在探讨血管紧张素II（ANG II）是否参与了脱水大鼠脂多糖（LPS）诱导发热的增强作用。结果表明，静脉注射LPS使脱水大鼠发热，其发热程度明显高于正常水合大鼠。在脱水条件下，增强LPS诱导的发热显着抑制血管紧张素转换酶（ACE）抑制剂。从上述结果来看，ANG II似乎很可能参与了在脱水条件下LPS诱导的促炎细胞因子的产生。为了测试这种可能性，我们接下来检测了ACE抑制剂和1型ANG II受体（AT_1-受体）拮抗剂对脱水大鼠中LPS诱导的促炎细胞因子白细胞介素-1（IL-1）和IL-6产生的影响。注射LPS可诱导肝脏IL-1β mRNA表达显著增加，而ACE抑制剂预处理可显著减弱这种作用。ACE抑制剂可降低LPS诱导的肝脏IL-1β蛋白浓度升高。AT_1受体拮抗剂在LPS前给药，可明显降低肝脏IL-1β浓度的升高。此外，ACE抑制剂减少了LPS诱导的IL-6血浆浓度的增加。上述结果提示，ANG Ⅱ及其AT_1受体在LPS诱导的促炎细胞因子的产生中起重要作用，而脱水大鼠LPS诱导的发热增强是由于ANG Ⅱ分泌增加刺激细胞因子的产生所致。

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.