We previously reported that brain angiotensin II type 2 (AT(2)) receptors contribute to the hyperthermia induced by intrahypothalamic (intrapreoptic (i.p.o.)) administration of prostaglandin E-2 (PGE(2)) in rats. The present study was carried out to investigate the role of angiotensin II (ANG II) receptors in the cardiovascular and adrenocorticotropic hormone (ACTH) responses induced in rats by i.p.o. injection of PGE(2). PGE(2) (100 ng) produced marked increases in blood pressure, heart rate, and plasma ACTH concentration. These changes were significantly enhanced by i.p.o. treatment with an AT(1)-receptor antagonist, losartan, while an AT(2)-receptor antagonist, CGP 42112A, had no effect. In contrast, losartan, but not CGP 42112A reduced the presser and ACTH responses to i.p.o, injection of a large dose of "exogenous" ANG II (25 ng). These results suggest that while "endogenous" ANG II exerts inhibitory effects on both the cardiovascular and the ACTH responses to i.p.o. PGE(2) by way of preoptic AT(1)-receptors, a large dose of exogenous ANG II produces effects opposite to those induced by the endogenous ANG II that is released locally and in small amounts by i.p.o. PGE(2). (C) 2000 Elsevier Science B.V. All rights reserved.