PT  - JOURNAL ARTICLE
AU  - Shimizu, Hideki
AU  - Miyoshi, Michio
AU  - Matsumoto, Kenji
AU  - Goto, Osamu
AU  - Imoto, Toshiaki
AU  - Watanabe, Tatsuo
TI  - The Effect of Central Injection of Angiotensin-Converting Enzyme Inhibitor and the Angiotensin Type 1 Receptor Antagonist on the Induction by Lipopolysaccharide of Fever and Brain Interleukin-1β Response in Rats
AID  - 10.1124/jpet.103.060392
DP  - 2004 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 865--873
VI  - 308
IP  - 3
4099  - http://jpet.aspetjournals.org/content/308/3/865.short
4100  - http://jpet.aspetjournals.org/content/308/3/865.full
SO  - J Pharmacol Exp Ther2004 Mar 01; 308
AB  - We recently reported an involvement of peripheral angiotensin II (ANG II) in the development of both the fever and the peripheral interleukin (IL)-1β 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-1β production in the rat brain induced by 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-1β. 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-1β (i.c.v.)-induced fever, whereas the AT1 receptor antagonist enhanced (rather than reduced) it. The AT1 receptor antagonist had no effect on the brain levels of prostaglandin E2 in rats given an i.c.v. injection of IL-1β. These results suggest that in rats, brain ANG II and AT1 receptors are involved in the LPS-induced production of brain IL-1β, thus contributing to the fever induced by the presence of LPS within the brain. The American Society for Pharmacology and Experimental Therapeutics