Braszko Jan J
Department of Clinical Pharmacology, Medical Academy of Bialystok, Bialystok, Poland.
Clin Exp Hypertens. 2005 Nov;27(8):635-49. doi: 10.1080/10641960500298723.
This study explores behavioral effects of angiotensin II (Ang II) and a potent AT(1) receptor inhibitor valsartan ((S)-N-valeryl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl}-valine). Male Wistar rats (160-180 g) were administered valsartan (10 mg/kg) orally followed, 2 hr later, by Ang II (1 nmol) given intracerebroventricularly (i.c.v., right lateral ventricle). Then 15 min later rats underwent behavioral testing: acquisition of conditioned avoidance responses (CARs), recall of a passive avoidance behavior, open field, elevated "plus" maze, and "chimney" test. Object recognition was tested 60 min after the i.c.v. injections. In addition, effect of valsartan on Ang II stimulated drinking of water was tested. We found that valsartan did not modify the Ang II facilitation of CARs acquisition but abolished the Ang II improvement of memory retrieval and consolidation. The lack of effect of our treatments on the rats' motor activity in the open field makes unspecific contribution of the drug-induced performance changes to the cognitive tests improbable. The anxiogenic action of Ang II, decreased by valsartan, makes an unspecific influence of anxiety possible. The prevention of Ang II increase of drinking by orally given valsartan confirmed effective blockade of the brain AT(1) receptors by the drug.
valsartan appears to affect cognitive effects of i.c.v. Ang II in rats in a similar way to losartan; anxiolytic activity of valsartan appears to be slightly weaker than that of losartan.
本研究探讨了血管紧张素II（Ang II）和一种强效AT(1)受体抑制剂缬沙坦（(S)-N-戊酰基-N-{[2'-(1H-四氮唑-5-基)联苯-4-基]-甲基}-缬氨酸）的行为效应。雄性Wistar大鼠（160 - 180克）口服缬沙坦（10毫克/千克），2小时后，通过脑室内（i.c.v.，右侧脑室）注射Ang II（1纳摩尔）。然后15分钟后，大鼠进行行为测试：条件性回避反应（CARs）的习得、被动回避行为的回忆、旷场试验、高架“十字”迷宫试验和“烟囱”试验。在脑室内注射后60分钟测试物体识别。此外，测试了缬沙坦对Ang II刺激饮水的影响。我们发现缬沙坦没有改变Ang II对CARs习得的促进作用，但消除了Ang II对记忆检索和巩固的改善作用。我们的处理对大鼠在旷场试验中的运动活动缺乏影响，使得药物诱导的行为变化对认知测试的非特异性贡献不太可能。缬沙坦降低了Ang II的致焦虑作用，使得焦虑的非特异性影响成为可能。口服缬沙坦预防Ang II引起的饮水增加，证实了该药物对脑AT(1)受体的有效阻断。
缬沙坦似乎以与氯沙坦相似的方式影响大鼠脑室内注射Ang II的认知效应；缬沙坦的抗焦虑活性似乎略弱于氯沙坦。
