Kaschina Elena, Schrader Felix, Sommerfeld Manuela, Kemnitz Ulrich Rudolf, Grzesiak Aleksandra, Krikov Maxim, Unger Thomas
Center for Cardiovascular Research (CCR)/Institute of Pharmacology, Charité Universitätsmedizin Berlin, Berlin, Germany.
J Hypertens. 2008 Dec;26(12):2361-73. doi: 10.1097/HJH.0b013e328313e547.
We investigated the effects of treatment with the angiotensin II type 1 receptor antagonist, telmisartan, on abdominal aortic aneurysm formation in normotensive rats.
Abdominal aortic aneurysm was induced by perfusion of an isolated aortic segment with elastase. Treatment with telmisattan (0.5 mg/kg per day) or hydralazine (15 mg/kg per day) was started after surgery and continued for 14 days. Sham-operated animals and vehicle-treated animals after aneurysm induction served as controls. Aortic diameter was measured using ultrasound before aneurysm induction and on days 7 and 14 after aneurysm induction.
On day 14, aortic diameter was increased two-fold in the vehicle-treated group compared to sham-operated animals (2.02 +/- 0.12 vs. 0.87 +/- 0.02 mm, P < 0.005, n = 8). Telmisartan treatment significantly reduced aneurysmal size (1.65 +/- 0.06 vs. 2.02 +/- 0.12 mm in vehicle, P < 0.05, n = 8), whereas treatment with hydralazine had no effect. Matrix metallopeptidase 3, cathepsin D, nuclear factor kappa B, tumour necrosis factor alpha, transforming growth factor-1 beta, as well as caspase 3, p53 and Fas ligand proteins, were significantly downregulated in aortic tissue under telmisartan compared to vehicle treatment. Serum monocyte chemoattractant protein 1 levels were also significantly decreased. Telmisartan and hydralazine reduced blood pressure to a similar extent within the observation period.
The angiotensin II type 1 receptor antagonist, telmisartan, prevents abdominal aortic aneurysm progression independently of blood pressure reduction by inhibiting proteolysis, apoptosis and inflammation in aortic tissue.
我们研究了1型血管紧张素II受体拮抗剂替米沙坦对正常血压大鼠腹主动脉瘤形成的影响。
通过用弹性蛋白酶灌注分离的主动脉段诱导腹主动脉瘤。术后开始用替米沙坦（每天0.5毫克/千克）或肼屈嗪（每天15毫克/千克）治疗，并持续14天。假手术动物和动脉瘤诱导后用赋形剂处理的动物作为对照。在动脉瘤诱导前以及诱导后第7天和第14天使用超声测量主动脉直径。
在第14天，与假手术动物相比，赋形剂处理组的主动脉直径增加了两倍（2.02±0.12对0.87±0.02毫米，P<0.005，n = 8）。替米沙坦治疗显著减小了动脉瘤大小（1.65±0.06对赋形剂组的2.02±0.12毫米，P<0.05，n = 8），而肼屈嗪治疗无效。与赋形剂处理相比，替米沙坦处理的主动脉组织中基质金属肽酶3、组织蛋白酶D、核因子κB、肿瘤坏死因子α、转化生长因子-1β以及半胱天冬酶3、p53和Fas配体蛋白显著下调。血清单核细胞趋化蛋白1水平也显著降低。在观察期内，替米沙坦和肼屈嗪降低血压的程度相似。
1型血管紧张素II受体拮抗剂替米沙坦通过抑制主动脉组织中的蛋白水解、细胞凋亡和炎症，独立于血压降低预防腹主动脉瘤进展。
