Protective effect of the inhibition of the renin-angiotensin system on aging
Protective effect of the inhibition of the renin-angiotensin system on aging
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DOI：
10.1016/j.regpep.2004.12.027
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发表时间：
2005-06-30
影响因子：
--
通讯作者：
Inserra, F
中科院分区：
文献类型：
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作者：
Basso, N;Paglia, N;Inserra, F
实验研究表明，慢性长期抑制肾素-血管紧张素系统（RAS）可以防止大多数的有害影响，由于老化的心血管系统和肾脏的正常小鼠和大鼠。在这篇综述中，我们的研究小组在过去几年中进行的几项研究提供了关于这个问题的所有信息进行了描述。在断奶后或12月龄（约为大鼠正常寿命的一半）时开始给药。用转换酶抑制剂依那普利或血管紧张素Ⅱ 1型（AT 1）受体阻滞剂氯沙坦抑制RAS。还在断奶后给药大鼠和未给药对照大鼠中测定了10和18月龄时的认知行为、情绪和自发活动，以阐明血管紧张素II在记忆功能障碍中的作用。在12至18月龄的给药动物中获得了类似的观察结果。结果表明，对所有治疗动物的心血管系统、肾脏和大脑的功能和结构具有显著的保护作用。在12月龄时观察到的损伤不是非常显著，但给药阻止了未给药动物中明显的进一步恶化。依那普利或氯沙坦治疗检测到的结果的相似性清楚地表明，大多数作用是通过AT 1受体发挥的。一氧化氮和抗氧化酶系统的分析表明，保护作用与RAS抑制剂的抗氧化作用和减少活性氧的形成有关。AngII抑制可能导致氧化应激机制的改变，特别是在线粒体水平。防止线粒体减少和/或损伤将与正常衰老过程的延迟有关。(c)2004 Elsevier B. V.保留所有权利。
Experimental studies indicate that chronic long-term inhibition of the renin-angiotensin system (RAS) can prevent most of the deleterious effects due to aging in the cardiovascular system and in the kidney of the normal mouse and rat. In this review, all the information available on this subject provided by several studies performed by our research group during the last years is been described. Treatment was initiated either after weaning or at 12 months of age that is about half the normal life span of the rat. A converting enzyme inhibitor: enalapril or an angiotensin II type 1 (AT1) receptor blocker: losartan were used to inhibit the RAS. Cognitive behaviour, emotionality, and locomotor activity were also determined at 10 and 18 months of age in treated since weaning and untreated control rats to elucidate the participation of angiotensin II in memory disfunction. A similar observation was obtained in animals treated from 12 to 18 months of age. Results have demonstrated a significant protective effect on the function and the structure of the cardiovascular system, the kidney and the brain in all the treated animals. Damage observed at 12 months of age was not very significant, but treatment stop further deterioration that was evident in untreated animals. The similarity of the results detected with either enalapril or losartan treatment, clearly indicates that most of the effects are exerted through AT1 receptors. Analysis of the nitric oxide and antioxidant enzymes systems suggest that the protective effect is related to an antioxidant action of the RAS inhibitors and a reduced formation of reactive oxygen species. AngII inhibition might produce changes in the mechanisms of oxidative stress specially at the mitochondrial level. Prevention of mitochondrial decrease and/or damage would be related with the delay of the normal aging process. (c) 2004 Elsevier B.V. All rights reserved.