1 Pharmacodynamics and Clinical Pharmacy Department, Faculty of Pharmacy, "Grigore T. Popa" University of Medicine and Pharmacy, Iaşi, Romania.
2 Center of Biomedical Research, Romanian Academy, Iasi, Romania.
Am J Alzheimers Dis Other Demen. 2019 Aug;34(5):329-336. doi: 10.1177/1533317519847042. Epub 2019 May 19.
This study was designed to evaluate the spatial working memory (as studied in Y-maze) or short-term and long-term spatial memory (assessed in radial 8 arms-maze task), in a scopolamine-induced memory deficits model in mice, by the oral administration of 2 angiotensin-converting enzyme inhibitors-captopril and ramipril and also the effects of the AT1 receptor antagonist, losartan. The present article was initiated as a reaction to the clinical setting of hypertensive disease, which involves lifelong administration of antihypertensive drugs, dietary or lifestyle constraints, and aging, which all take a toll on the higher functions of the nervous system. Most of the patients with cognitive decline suffer of various metabolic imbalances, hypertension, cardiac and kidney disease, many of them which are treated with oral administration of Renin-angiotensin aldosterone system-altering agents like those presented above. Our results showed a protective effect of captopril, ramipril, and losartan prescopolamine administration on spontaneous alternation in Y-maze task, as compared to scopolamine-alone treated mice, as well as decreased number of working memory errors and reference memory errors in radial-arm maze for both losartan + scopolamine and ramipril + scopolamine groups versus scopolamine alone. This could have a therapeutical relevance, especially since oral administration was preferred in our report, as it is used in the therapeutic procedures in humans, further enhancing the similarities with the clinical conditions.
本研究旨在通过口服给予 2 种血管紧张素转换酶抑制剂卡托普利和雷米普利以及 AT1 受体拮抗剂氯沙坦,评估东莨菪碱诱导的记忆缺陷模型中小鼠的空间工作记忆(如在 Y 迷宫中研究)或短期和长期空间记忆(在放射状 8 臂迷宫任务中评估)。本文的出发点是针对高血压病的临床情况,其中涉及到终身服用抗高血压药物、饮食或生活方式限制以及衰老,所有这些都会对神经系统的高级功能造成损害。大多数认知能力下降的患者患有各种代谢失衡、高血压、心脏和肾脏疾病,其中许多患者通过口服给予肾素-血管紧张素-醛固酮系统改变剂(如上面提到的那些)进行治疗。我们的结果显示,与单独给予东莨菪碱的小鼠相比,卡托普利、雷米普利和氯沙坦预先给予东莨菪碱可保护自发交替在 Y 迷宫任务中的作用,并且氯沙坦+东莨菪碱和雷米普利+东莨菪碱组的工作记忆错误和参考记忆错误的数量均减少,与单独给予东莨菪碱相比。这可能具有治疗相关性,特别是因为在我们的报告中优选了口服给药,因为它在人类的治疗程序中使用,进一步增强了与临床情况的相似性。