Angiotensin II: its effects on fever and hypothermia in systemic inflammation.
Angiotensin II (ANG II), a bioactive peptide that plays important roles in blood-pressure and body-fluid regulation, has recently been reported to be involved in normal thermoregulation and fever. In the case of thermoregulation, ANG II lowers body temperature when administered centrally or systemically (i.e. "exogenous" ANG II acts as a hypothermia-inducing agent). In contrast, "endogenous" ANG II is involved both in heat-loss responses in a hot environment and in thermogenesis in the cold. It therefore seems likely that endogenous ANG II is involved in maintaining body temperature at the set-point. In the case of fever, it has been reported that endogenous brain ANG II and its type 1 receptor mediate or modulate the fever induced by "restraint stress". At the final step in "pyrogen-induced" fever, brain ANG II facilitates the fever induced by prostaglandin E2 (PGE2) through its action on the type 2 receptor, whereas at its first step the lipopolysaccharide (LPS, 2 microg/kg, i.v.)-induced production of pyrogenic cytokines [such as interleukin-1 (IL-1)] involves an action of endogenous ANG II through its type 1 receptor. On the other hand, it is well known that a very high dose of LPS (50-5000 microg/kg) injected systemically induces hypothermia in rodents. This hypothermia is presumably initiated by tumor necrosis factor (TNF). Since ANG II contributes to the LPS-induced production of cytokines such as IL-1beta, as described above, it is possible that the generation of TNF by LPS involves an action of ANG II, too, and that this TNF production leads to the LPS-induced hypothermia. Together, these findings suggest that ANG II and its receptors make a number of contributions to normal thermoregulation, to fever, and to the hypothermia in systemic inflammation.
Watanabe
Tatsuo
T
Division of Integrative Physiology, Department of Functional, Morphological and Regulatory Science, Tottori University Faculty of Medicine, Yonago, Tottori 683, Japan. watanabe@grape.med.tottori-u.ac.jp
Miyoshi
Michio
M
Imoto
Toshiaki
T
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D005334:Fever / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D007035:Hypothermia / Q000209:etiology* / Q000378:metabolism; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications* / Q000378:metabolism
D000804:Angiotensin II