Modifications in basal and stress-induced hypothalamic AMP-activated protein kinase (AMPK) activity in rats chronically treated with an angiotensin II receptor blocker
Modifications in basal and stress-induced hypothalamic AMP-activated protein kinase (AMPK) activity in rats chronically treated with an angiotensin II receptor blocker
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DOI：
10.3109/10253890.2011.648673
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发表时间：
2012-09-01
影响因子：
2.3
通讯作者：
Korbonits, Marta
中科院分区：
文献类型：
--
作者：
Marques, Mirna B.;Ribeiro-Oliveira, Antonio, Jr.;Korbonits, Marta
5'腺苷单磷酸活化蛋白激酶（AMPK）作为代谢应激传感器发挥着重要作用。下丘脑AMPK在约束和手术应激反应中的作用尚未被研究过。最近有研究表明，肾素-血管紧张素系统除了在应激调节中发挥作用外，还可能在调节代谢途径中发挥重要作用，包括调节AMPK系统。因此，本研究旨在评估坎地沙坦（一种血管紧张素II AT1受体阻滞剂）在基础条件下、清醒大鼠受限后或全麻手术应激后对下丘脑AMPK活性的影响。雄性Wistar大鼠饮水中给予坎地沙坦5 mg/kg/d，连续2周。下丘脑AMPK活性测定在基础和应激条件下，使用激酶活性测定。长期给药坎地沙坦显著增加下丘脑AMPK活性。下丘脑AMPK活性也在约束应激下增加，而在麻醉下的手术应激下没有观察到变化。在坎地沙坦治疗的大鼠中观察到的高水平下丘脑AMPK激活并未因约束应激而改变，但通过麻醉和手术降低到控制水平。综上所述，在有意识的大鼠中，慢性坎地沙坦治疗和约束应激刺激下丘脑AMPK活性，而麻醉下的手术应激甚至在坎地沙坦治疗的大鼠中抑制调节AMPK活性的途径。
5' adenosine monophosphate-activated protein kinase (AMPK) plays a prominent role as a metabolic stress sensor. The role of hypothalamic AMPK in response to restraint and surgical stress has not been previously investigated. It has been recently suggested that the renin-angiotensin system, in addition to its role in stress regulation, may play a significant role in regulating metabolic pathways including the regulation of the AMPK system. This study was thus aimed to evaluate the effects of candesartan, an angiotensin II AT1 receptor blocker drug, on hypothalamic AMPK activity under basal conditions and after restraint in conscious rats or after surgical stress under general anesthesia. Male Wistar rats were treated with 5 mg/kg/day candesartan in the drinking water for 2 weeks. The hypothalamic AMPK activity was determined under basal and stress conditions, using a kinase activity assay. Chronic administration of candesartan significantly increased hypothalamic AMPK activity. Hypothalamic AMPK activity was also increased by restraint stress whereas no change was observed during surgical stress under anesthesia. The high levels of hypothalamic AMPK activation observed in candesartan-treated rats were not changed by restraint stress but were reduced to control levels by anesthesia and surgery. In conclusion, chronic candesartan treatment and restraint stress in conscious rats stimulate the hypothalamic AMPK activity, whereas surgical stress under anesthesia inhibits pathways regulating the AMPK activity even in candesartan-treated rats.