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Am J Physiol Regul Integr Comp Physiol 284: R1092-R1097, 2003; doi:10.1152/ajpregu.00700.2002
0363-6119/03 $5.00
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Vol. 284, Issue 4, R1092-R1097, April 2003

ANG II is involved in the LPS-induced production of proinflammatory cytokines in dehydrated rats

Michio Miyoshi, Katsumi Nagata, Toshiaki Imoto, Osamu Goto, Akiko Ishida, and Tatsuo Watanabe

The Department of Physiology, Tottori University Faculty of Medicine, Yonago, Tottori 683, Japan

We have previously reported results that led us to speculate that ANG II is involved in the LPS-induced production of proinflammatory cytokines, especially under dehydrated conditions. To test this possibility, in this study we examined the effects of an angiotensin-converting enzyme (ACE) inhibitor and an antagonist of the type-1 ANG II receptor (AT1 receptor) on the LPS-induced production of the proinflammatory cytokines IL-1 and IL-6 in dehydrated rats. A single intravenous injection of LPS induced a marked increase in the expression of IL-1beta mRNA in the liver, an effect that was significantly attenuated by pretreatment with the ACE inhibitor. Furthermore, the ACE inhibitor reduced the LPS-induced increase in the hepatic concentration of IL-1beta protein. When the AT1-receptor antagonist was given intravenously before the LPS, the increase in the hepatic concentration of IL-1beta was significantly reduced. Finally, the ACE inhibitor reduced the LPS-induced increase in the plasma concentration of IL-6. These results represent the first in vivo evidence that ANG II and its AT1 receptor play important roles in the production of proinflammatory cytokines that is induced by LPS under dehydrated conditions.

interleukin-1; interleukin-6; fever


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