Bali Anjana, Jaggi Amteshwar Singh
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
Life Sci. 2015 Nov 15;141:90-8. doi: 10.1016/j.lfs.2015.09.005. Epub 2015 Sep 18.
The present study aimed to investigate the role of angiotensin II in repeated immobilization stress exposure of varying duration.
Mice were subjected either to short (30min) or long duration (120min) immobilization stress for 5days. The behavioral changes were assessed by actophotometer, hole board, open field and social interaction tests on day 1 and day 5. The serum corticosterone levels were measured as an index of HPA axis on day 5.
A single exposure of short or long duration stress produced behavioral deficits and increased corticosterone levels. However, repeated exposure of stressors was followed by restoration of behavioral and biochemical changes, suggesting the development of stress adaptation. A single administration of telmisartan (5mg/kg) exacerbated the short stress-induced decrease in behavioral activity and increase in corticosterone levels on the first day of stress exposure, suggesting the anti-stress role of angiotensin II. In contrast, the normalization of behavioral and biochemical response was observed in prolonged stress-subjected mice following telmisartan treatment on the 1st day of stress exposure, suggesting stress inducing action of angiotensin II. Furthermore, telmisartan treatment for 5days abolished the restoration of behavioral and biochemical response following 5 consecutive exposures of short immobilization stress, without altering stress adaptation in prolonged stress, suggesting that angiotensin II has stress adaptive role in short stress.
It is concluded that angiotensin II acts as anti-stress agent and promotes adaptation during short stress, whereas it acts as stress promoting agent, without affecting stress adaptation during prolonged stress.
本研究旨在探讨血管紧张素II在不同时长反复固定应激暴露中的作用。
将小鼠分别进行短时间(30分钟)或长时间(120分钟)的固定应激处理,持续5天。在第1天和第5天通过活动光度计、洞板试验、旷场试验和社交互动试验评估行为变化。在第5天测量血清皮质酮水平作为下丘脑-垂体-肾上腺(HPA)轴的指标。
单次短时间或长时间应激暴露会导致行为缺陷并使皮质酮水平升高。然而,反复应激暴露后行为和生化变化得以恢复,提示应激适应的形成。在应激暴露第一天单次给予替米沙坦(5毫克/千克)会加剧短时间应激诱导的行为活动减少和皮质酮水平升高,提示血管紧张素II的抗应激作用。相反,在应激暴露第一天给予替米沙坦治疗后,长时间应激处理的小鼠行为和生化反应恢复正常,提示血管紧张素II的应激诱导作用。此外,连续5天给予替米沙坦治疗可消除连续5次短时间固定应激暴露后行为和生化反应的恢复,但不改变长时间应激下的应激适应,提示血管紧张素II在短时间应激中具有应激适应作用。
得出结论,血管紧张素II在短时间应激中作为抗应激剂发挥作用并促进适应,而在长时间应激中它作为应激促进剂发挥作用,且不影响应激适应。