Wincewicz Dominik, Braszko Jan J
Department of Clinical Pharmacology, Medical University of Bialystok, Białystok, Poland.
Department of Clinical Pharmacology, Medical University of Bialystok, Białystok, Poland.
Pharmacol Rep. 2014 Jun;66(3):436-41. doi: 10.1016/j.pharep.2013.11.002. Epub 2014 Apr 2.
The potential effect of chronic treatment with telmisartan, an angiotensin type 1 receptor blocker (ARB) and partial agonist of peroxisome proliferator--activated receptor γ (PPARγ), on stress-related disorders is a matter of considerable interest. The existing data suggest that angiotensin II (Ang II) plays a major role in exaggerated sympathetic and hormonal response to stress. Enhanced formation of Ang II and increased AT1 receptor activity is associated with devastating impact of stress on central nervous system, which may trigger many psychiatric disorders such as depression, schizophrenia or post-traumatic stress disorder. Some of the anti-stress effects of ARBs have already been proven but these on the stress-induced cognitive impairment were examined only for candesartan. In this study, we tested a hypothesis that blockade of stress response by another ARB telmisartan alleviates the negative effect of prolonged restraint stress on cognitive functions of male Wistar rats.
The preventive action of long-lasting treatment with telmisartan (1mg/kg body weight) against impairment caused by chronic stress (2h daily for 21 days) on recall was evaluated in a passive avoidance (PA) situation and object recognition test (ORT). Locomotor activity and anxiety behavior were tested respectively, in an open field and an elevated plus-maze.
The results of this study indicate that telmisartan diminishes deleterious effects of chronic restraint stress on memory in a statistically significant manner (p<0.01) in both, PA situation and ORT.
It appears that telmisartan may constitute a new therapeutic option in a stress-related cognitive impairment.
替米沙坦是一种血管紧张素1型受体阻滞剂（ARB），也是过氧化物酶体增殖物激活受体γ（PPARγ）的部分激动剂，其长期治疗对与应激相关疾病的潜在影响备受关注。现有数据表明，血管紧张素II（Ang II）在对应激的过度交感神经和激素反应中起主要作用。Ang II生成增加和AT1受体活性增强与应激对中枢神经系统的破坏性影响相关，这可能引发许多精神疾病，如抑郁症、精神分裂症或创伤后应激障碍。ARB的一些抗应激作用已得到证实，但仅对坎地沙坦进行了其对应激诱导的认知障碍影响的研究。在本研究中，我们测试了一个假设，即另一种ARB替米沙坦阻断应激反应可减轻长期束缚应激对雄性Wistar大鼠认知功能的负面影响。
在被动回避（PA）实验和物体识别测试（ORT）中，评估替米沙坦（1mg/kg体重）长期治疗对慢性应激（每天2小时，持续21天）所致记忆损伤的预防作用。分别在旷场和高架十字迷宫中测试运动活动和焦虑行为。
本研究结果表明，在PA实验和ORT中，替米沙坦均能以统计学显著方式（p<0.01）减轻慢性束缚应激对记忆的有害影响。
替米沙坦似乎可能成为治疗应激相关认知障碍的一种新的治疗选择。
