Vol. 282, Issue 2, 873-881, 1997

The Effect of Central Angiotensin II Receptor Blockade on Interleukin-1- and Prostaglandin E-Induced Fevers in Rats: Possible Involvement of Brain Angiotensin II Receptor in Fever Induction¹

Tatsuo Watanabe, Yukio Saiki and Yoshiyuki Sakata

The Department of Physiology, Yamaguchi University School of Medicine, Ube Yamaguchi 755, Japan

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-1 (IL-1) or prostaglandin E₂ (PGE₂). Intraperitoneal (i.p.) injection of IL-1 (2 µg/kg) induced a marked fever of rapid onset. Intracerebroventricular (i.c.v.) administration, immediately before IL-1 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-1 (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-1 (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.