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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on November 14, 2003; DOI: 10.1124/jpet.103.060392

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Received for publication September 22, 2003.
Revised October 27, 2003.
Accepted for publication November 4, 2003.

The effect of central injection of angiotensin-converting enzyme inhibitor and the AT1-receptor antagonist on the induction by LPS of fever and brain interleukin-1{beta} response in rats

Hideki Shimizu 1, Michio Miyoshi 1, Kenji Matsumoto 2, Osamu Goto 3, Toshiaki Imoto 1, Tatsuo Watanabe 1*

1 Tottori University Faculty of Medicine 2 Osaka University 3 Tokyo University

* Address correspondence to: E-mail: watanabe{at}grape.med.tottori-u.ac.jp

Abstract

We recently reported an involvement of peripheral angiotensin II (ANG II) in the development of both the fever and the peripheral interleukin-1{beta} (IL-1 {beta}) production induced in rats by a systemic injection of lipopolysaccharide (LPS). The present study was performed to investigate whether brain ANG II contributes to the fever and IL-1{beta} production in the rat brain induced by intracerebroventricular (i.c.v.) injection of LPS. LPS (0.2 and 2 µg, i.c.v.) induced dose-related fevers and increases in the brain (hypothalamus, hippocampus, and cerebellum) concentrations of IL-1{beta}. These effects were significantly inhibited by i.c.v. administration of either an angiotensin-converting-enzyme (ACE) inhibitor or an angiotensin type-1 (AT1)-receptor antagonist. By contrast, the ACE inhibitor had no effect on the IL-1{beta} (i.c.v.)-induced fever, while the AT1-receptor antagonist enhanced (rather than reduced) it. The AT1-receptor antagonist had no effect on the brain levels of prostaglandin E2 (PGE2) in rats given an i.c.v. injection of IL-1{beta}. These results suggest that in rats, brain ANG II and AT1 receptors are involved in the LPS-induced production of brain IL-1{beta}, thus contributing to the fever induced by the presence of LPS within the brain.


Key words: Angiotensin II, Brain, Fever, Hypothalamus, IL-1, LPS


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