Angiotensin II: its effects on fever and hypothermia in systemic inflammation.
Angiotensin II: its effects on fever and hypothermia in systemic inflammation.
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DOI：
10.2741/1243
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
Tatsuo Watanabe;M. Miyoshi;T. Imoto
中科院分区：
文献类型：
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作者：
Tatsuo Watanabe;M. Miyoshi;T. Imoto
血管紧张素II(Ang II)是一种在血压和体液调节中起重要作用的生物活性多肽，最近被报道参与正常体温调节和发热。在体温调节方面，血管紧张素转换酶II在中央或全身应用时可降低体温(即“外源性”血管紧张素转换酶II可起到低温诱导剂的作用)。相反，“内源性”血管紧张素Ⅱ既参与热环境中的热损失反应，也参与冷环境中的产热。因此，内源性血管紧张素转换酶II可能参与维持体温在设定点。在发热的情况下，据报道，内源性脑血管紧张素II及其1型受体介导或调节“束缚应激”引起的发热。在热原诱导的发热的最后一步，脑血管紧张素II通过作用于2型受体而促进前列腺素E2(PGE2)引起的发热，而在其第一步，内毒素(LPS，2微克/公斤，静脉注射)诱导的致热细胞因子[如白细胞介素1(IL-1)]的产生涉及内源性血管紧张素II通过其1型受体的作用。另一方面，众所周知，注射非常高剂量的内毒素(50-5000微克/公斤)会引起啮齿类动物全身体温下降。这种体温过低可能是由肿瘤坏死因子(TNF)引起的。如上所述，由于血管紧张素Ⅱ参与了内毒素诱导的细胞因子如IL-1β的产生，因此，内毒素产生的肿瘤坏死因子也可能也参与了血管紧张素Ⅱ的作用，并且这种产生的肿瘤坏死因子导致了内毒素诱导的低温。综上所述，这些发现表明，Ang II及其受体在正常体温调节、发热和全身炎症的体温降低中起着重要作用。
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.