Abstract

We investigated the role of the brain angiotensin II (Ang II) receptor subtypes AT₁ and AT₂ in the development of fever induced in freely moving rats by administration of interleukin-1β (IL-1β) or prostaglandin E₂(PGE₂). Intraperitoneal (i.p.) injection of IL-1β (2 μg/kg) induced a marked fever of rapid onset. Intracerebroventricular (i.c.v.) administration, immediately before IL-1β injection, of a selective AT₂ receptor antagonist, CGP42112A (5 or 20 μg), reduced the fever in a dose-related manner. Rats given an i.c.v. injection of PGE₂ (200 ng) developed a monophasic fever response that was attenuated by i.c.v. treatment with CGP42112A (10 or 20 μg) in a dose-related manner. The IL-1β (2 μg/kg i.p.)- and PGE₂ (200 ng i.c.v.)-induced fevers were unchanged by the selective AT₁ receptor antagonist losartan (60 μg i.c.v.). Treatment with exogenous Ang II (100 ng i.c.v.), which itself had no effect on resting body temperature, resulted in an enhancement of the PGE₂ (50 ng i.c.v.)-induced fever. The administration of CGP42112A (2 and 5 μg) into the rostral hypothalamus (preoptic/anterior hypothalamic region) reduced fevers induced by IL-1β (2 μg/kg i.p.) or intrahypothalamic (i.h.) PGE₂ (100 ng). Moreover, i.h. injection of Ang II (25 ng) augmented the PGE₂ (25 ng i.h.)-induced fever. Finally, the i.h. administration, 15 min before i.h. PGE₂ (100 ng), of the angiotensin-converting enzyme (ACE) inhibitor lisinopril (5 and 10 μg) attenuated the PGE₂-induced fever. These results suggest that brain AT₂ receptors contribute to the induction of such febrile responses in rats.