Protective effect of long-term angiotensin II inhibition
Protective effect of long-term angiotensin II inhibition
复制标题
DOI：
10.1152/ajpheart.00393.2007
复制
发表时间：
2007-09-01
影响因子：
4.8
通讯作者：
Inserra, Felipe
中科院分区：
文献类型：
--
作者：
Basso, Nidia;Cini, Rosa;Inserra, Felipe
实验研究表明，血管紧张素II （ANG II）通过其1型受体（AT(1)）促进心血管肥大和纤维化。因此，本研究的目的是分析慢性长期抑制肾素-血管紧张素系统（RAS）是否可以预防正常大鼠心血管系统中大部分因衰老而产生的有害影响。主要目的是比较两种阻断ANG II的策略：转换酶抑制剂（CEI）和AT(1)受体阻滞剂（AT(1)RB）。对照组不接受治疗；断奶后2周开始治疗。A CEI，依那普利（10 mg.kg -1）。天（-1），或AT(1)RB，氯沙坦（30 mg.kg(-1)）。day(-1))，用于抑制RAS。在整个实验期间记录收缩压、体重、水和食物摄入量。在6和18个月时进行心脏、主动脉和肠系膜动脉的重量以及心血管结构的组织学分析。三个实验组各20只动物允许自然死亡。结果表明，在所有治疗过的动物中，对心血管系统的功能和结构都有显著的保护作用。在18月龄时观察到心脏和主动脉的变化相当显著，但每次治疗都完全消除了这种恶化。依那普利和氯沙坦治疗结果的相似性清楚地表明，大多数作用是通过AT1受体发挥的。一个突出的发现是，与未治疗的对照组动物相比，两组治疗动物的寿命都有显著的相似延长。
Experimental studies indicate that angiotensin II (ANG II) through its type 1 receptor (AT(1)) promotes cardiovascular hypertrophy and fibrosis. Therefore, the aim of this study was to analyze whether chronic long-term inhibition of the renin-angiotensin system (RAS) can prevent most of the deleterious effects due to aging in the cardiovascular system of the normal rat. The main objective was to compare two strategies of ANG II blockade: a converting enzyme inhibitor (CEI) and an AT(1) receptor blocker (AT(1)RB). A control group remained untreated; treatment was initiated 2 wk after weaning. A CEI, enalapril (10 mg.kg(-1).day(-1)), or an AT(1)RB, losartan (30 mg.kg(-1).day(-1)), was used to inhibit the RAS. Systolic blood pressure, body weight, and water and food intake were recorded over the whole experimental period. Heart, aorta, and mesenteric artery weight as well as histological analysis of cardiovascular structure were performed at 6 and 18 mo. Twenty animals in each of the three experimental groups were allowed to die spontaneously. The results demonstrated a significant protective effect on the function and structure of the cardiovascular system in all treated animals. Changes observed at 18 mo of age in the hearts and aortas were quite significant, but each treatment completely abolished this deterioration. The similarity between the results detected with either enalapril or losartan treatment clearly indicates that most of the effects are exerted through AT1 receptors. An outstanding finding was the significant and similar prolongation of life span in both groups of treated animals compared with untreated control animals.