Angiotensin II and Fever in Rodents

Angiotensin II (ANG II), a bioactive peptide well known to play an important role in blood-pressure and body-fluid regulation, participates in inflammatory responses, too. Recently, we reported results suggesting that ANG II is involved in the development of the fever induced by intravenous (i.v.) injection of lipopolysaccharide (LPS, 2 ?g/kg) in dehydrated rats (in which the secretion of ANG II is elevated). Furthermore, we verified the contributions made by ANG II and its type 1 receptor (AT1 receptor) to the LPS-induced production of interleukin-1β ; (IL-1β) in those rats. It therefore seems likely that in rats, ANG II and its receptors contribute to the induction of this fever at its 1st step (namely, the LPS-induced production of pyrogenic cytokines such as IL-1β). Moreover, we have revealed that intrahypothalamic (i.h.) ANG II and AT2 receptors are involved in the development of the fever induced by i.h. injection of prostaglandin E2 (PGE2), a final fever mediator. ANG II given i.h., which had no effect on the resting body temperature, facilitated PGE2-induced fever. These results suggest that in rats, ANG II and its receptors contribute to the induction of fever at its final step, too (namely, the action of PGE2 to cause fever). Finally, a single i.p. injection of IL-1β results in a weaker IL-1β-induced fever in AT2-receptor-deficient mice than in wild-type mice, suggesting that the brain AT2 receptor is involved in the development of fever (possibly at its final step) in mice as well. Collectively, these results suggest that in rodents, ANG II and its receptors contribute to the development of fever, both at the 1st and final steps in the pathway for fever induction.