RT Journal Article SR Electronic T1 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 JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 865 OP 873 DO 10.1124/jpet.103.060392 VO 308 IS 3 A1 Hideki Shimizu A1 Michio Miyoshi A1 Kenji Matsumoto A1 Osamu Goto A1 Toshiaki Imoto A1 Tatsuo Watanabe YR 2004 UL http://jpet.aspetjournals.org/content/308/3/865.abstract 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