中国药理学通报2012，Vol.28Issue(1)：54-58,5.DOI:10.3969/j.issn.1001-1978.2012.013.
替米沙坦对高血压大鼠血管ACE2表达及氧化应激水平的影响
Effects of Telmisartan on vascular ACE2 expression and oxidative stress levels in spontaneously hypertensive rats
摘要
Abstract
Aim To investigate the influences of Telm-isartan on vascular expression of angiotensin-converting enzyme 2 ( ACE2 ), nitric oxide ( NO ) and oxidative stress levels in spontaneous hypertension rats ( SHR ). Methods 10-week SHR and Wistar-Kyoto ( WKY ) rats were treated with Telmisartan (5 or 10 mg 'kg-1 ? D-1 ) or placebo for 10 weeks. The protein and phosphorylation levels of ACE2 and endothelial NO synthase ( eNOS ) in the aortas from treated rats were determined with Western blotting methods. In addition , concentration of malonyldialdehyde ( MDA ) and NO in the rat aortas were determined with thiobarbitu-ric acid ( TBA ) reactive substances and the Greiss rea-gent , respectively. Results Compared with WKY rat, ACE2 protein and the phosphorylated Ser1177-eNOS level were significantly reduced in the SHR aortas ( ACE2:0. 39 ±0. 05 vs 1. 00 ±0. 06;p-eNOS: 0. 43 ± 0. 06 I? 1. 00 ± 0. 04 ;P < 0. 01, respectively ), accompanied by reduced NO level and elevated MDA content ( NO mmol ? G"1 protein: 11. 5 ± 2. 1 vs 27. 8 ±4. 9; MDA nmol ? G"1 protein: 393.9 ± 17.9 vs 186.3 ± 14. 5 ; P < 0. 01, respectively ). Treatment with low-and high-dose Telmisartan significantly enhanced ACE2 protein and the phosphorylated Ser1177-eNOS level in the SHR aortas ( ACE2: 0. 62 ± 0. 06, 0. 65 ± 0.07 is 0. 39±0. 05 ;p-eNOS:0. 68 ±0.07,0.71 ±0. 06 vs 0. 43 ± 0. 06; P < 0. 05 , respectively ), along with a marked increase in NO level ( 19. 2 ± 3. 3 ,23. 9 ± 3. 2 vs 11. 5 ±2. 1 mmol ? G-1 protein;P <0. 05 , respectively ) and an obvious reduction of MDA content ( 271. 9 ± 16. 1,249. 2 ± 19. 6 vs 393. 9 ± 17. 9 nmol ? G"1 protein; P < 0. 05 , respectively ). Conclusion Chronic Telmisartan treatment improves vascular expression of ACE2 and phosphorylation activation ofeNOS, contributing to the augmentation of NO generation and attenuation of oxidative stress levels in SHR, suggesting that Telmisartan has potential vascular protective effects in hypertension.关键词
替米沙坦/高血压/血管紧张素转换酶2/一氧化氮/氧化应激/血管保护Key words
telmisartan/ hypertension/ angiotensin-converting enzyme 2 ( ACE2 )/ nitric oxide/ oxidative stress/ vascular protection分类
医药卫生引用本文复制引用
金海燕,钟久昌,宋蓓,叶佳颖,张丽红,李宇琳,于茜,徐旭东,林国珍..替米沙坦对高血压大鼠血管ACE2表达及氧化应激水平的影响[J].中国药理学通报,2012,28(1):54-58,5.基金项目
国家自然科学基金资助项目(No 30973522,81170246) （No 30973522,81170246）
上海市浦江人才计划项目(No 11PJ1408300) （No 11PJ1408300）
上海交通大学医学院"新百人计划"项目 （）
