Sepehri Hamid, Ganji Farzaneh, Nazari Zahra, Vahid Marzieh
Department of Physiology, Neuroscience Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
Department of Biology, Faculty of Science, Golestan University, Gorgan, Iran.
Transl Neurosci. 2022 Apr 20;13(1):72-79. doi: 10.1515/tnsci-2022-0215. eCollection 2022 Jan 1.
The classical renin-angiotensin system (RAS) has an important role in the cardiovascular system and water homeostasis in the body. Recently, the existence of RAS with all of its components has been shown in the mammalian brain. RAS participates in many brain activities, including memory acquisition and consolidation. Since the cholinergic neurotransmission in the hippocampus is crucial for these functions, this study aims to evaluate the hippocampal angiotensin receptors (ATs) and choline acetyltransferase (ChAT) mRNA in the renovascular hypertensive rats in captopril- and losartan-treated hypertensive rats.
The rats were randomly divided into four groups of eight animals; sham, Goldblatt two kidney one clip (2K1C) hypertensive rats and Goldblatt 2K1C hypertensive rats received 5 mg/kg captopril and Goldblatt 2K1C hypertensive rats received 10 mg/kg losartan. After 8 days of treatment, the rats were sacrificed and angiotensin-converting enzyme (ACE), ChAT, AT1, and AT2 receptor mRNAs in the hippocampus of rats were assessed by real-time PCR. The Morris water maze test was applied to measure the cognitive functioning of the rats.
Hypertensive rats showed impaired acquisition and memory function in the Morris water maze test. Treatment with ACE inhibitor (captopril) and AT1 receptor antagonist (losartan) reversed the observed acquisition and memory deficit in hypertensive rats. Overexpression of AChE, AT1, and AT2 and low expression of ChAT were noted in the hippocampus of rats with Goldblatt hypertension compared with that of the sham group. Treatment with captopril significantly reversed these changes, while treatment with losartan slightly reduced the mentioned effects.
The memory-enhancing effect of captopril in renovascular hypertensive rats might lead to increased hippocampal ChAT expression.
经典肾素-血管紧张素系统(RAS)在心血管系统及机体水稳态中发挥重要作用。近来,已证实其所有组分在哺乳动物脑中均存在。RAS参与多种脑活动,包括记忆获取与巩固。鉴于海马体中的胆碱能神经传递对这些功能至关重要,本研究旨在评估卡托普利和氯沙坦治疗的肾血管性高血压大鼠海马体中的血管紧张素受体(ATs)及胆碱乙酰转移酶(ChAT)mRNA。
将大鼠随机分为四组,每组八只;假手术组、Goldblatt双肾单夹(2K1C)高血压大鼠组,Goldblatt 2K1C高血压大鼠接受5mg/kg卡托普利治疗组,以及Goldblatt 2K1C高血压大鼠接受10mg/kg氯沙坦治疗组。治疗8天后,处死大鼠,通过实时PCR评估大鼠海马体中的血管紧张素转换酶(ACE)、ChAT、AT1和AT2受体mRNA。应用Morris水迷宫试验测量大鼠的认知功能。
高血压大鼠在Morris水迷宫试验中表现出获取和记忆功能受损。用ACE抑制剂(卡托普利)和AT1受体拮抗剂(氯沙坦)治疗可逆转高血压大鼠中观察到的获取和记忆缺陷。与假手术组相比,Goldblatt高血压大鼠海马体中乙酰胆碱酯酶(AChE)、AT1和AT2过表达,ChAT表达降低。卡托普利治疗可显著逆转这些变化,而氯沙坦治疗则略微减轻上述作用。
卡托普利对肾血管性高血压大鼠的记忆增强作用可能导致海马体ChAT表达增加。