Tham Doris M, Martin-McNulty Baby, Wang Yi-Xin, Da Cunha Valdeci, Wilson Dennis W, Athanassious Christian N, Powers Andrew F, Sullivan Mark E, Rutledge John C
Department of Internal Medicine, School of Medicine, University of California at Davis, Davis 95616, USA.
Am J Physiol Regul Integr Comp Physiol. 2002 Dec;283(6):R1442-9. doi: 10.1152/ajpregu.00295.2002. Epub 2002 Sep 12.
Cardiovascular diseases, such as atherosclerosis and hypertension, are associated with arterial stiffening. Previous studies showed that ANG II exacerbated atherosclerosis and induced hypertension and aneurysm formation in apolipoprotein E-deficient (apoE-KO) mice. The aim of the present study was to examine the effects of chronic treatment of ANG II on the arterial elastic properties in apoE-KO mice. We hypothesized that ANG II will injure the arterial wall resulting in increased arterial stiffening. Male apoE-KO mice were infused with either ANG II (1.44 mg. kg(-1). day(-1)) or vehicle (PBS) for 30 days. ANG II treatment accelerated atherosclerosis in the carotid artery by sixfold (P < 0.001) and increased blood pressure by 30% (P < 0.05). Additionally, our data demonstrated that ANG II increased arterial stiffening using both in vivo and in vitro methods. ANG II significantly increased pulse wave velocity by 36% (P < 0.01) and decreased arterial elasticity as demonstrated by a more than 900% increase in maximal stiffening (high strain Young's modulus) compared with vehicle (P < 0.05). These functional changes were correlated with morphological and biochemical changes as demonstrated by an increase in collagen content (60%), a decrease in elastin content (74%), and breaks in the internal elastic lamina in the aortic wall. In addition, endothelium-independent vasorelaxation to sodium nitroprusside was impaired in the aortic rings of ANG II-treated mice compared with vehicle. Thus, the present data indicate that ANG II injures the artery wall in multiple ways and arterial stiffening may be a common outcome of ANG II-induced arterial damage.
心血管疾病，如动脉粥样硬化和高血压，与动脉僵硬有关。先前的研究表明，血管紧张素II（ANG II）会加剧动脉粥样硬化，并在载脂蛋白E缺陷（apoE-KO）小鼠中诱发高血压和动脉瘤形成。本研究的目的是检验长期给予ANG II对apoE-KO小鼠动脉弹性特性的影响。我们假设ANG II会损伤动脉壁，导致动脉僵硬加剧。雄性apoE-KO小鼠分别接受ANG II（1.44 mg·kg⁻¹·天⁻¹）或溶剂（PBS）灌注30天。ANG II治疗使颈动脉粥样硬化加速了6倍（P<0.001），血压升高了30%（P<0.05）。此外，我们的数据表明，ANG II使用体内和体外方法均增加了动脉僵硬。ANG II使脉搏波速度显著增加了36%（P<0.01），并降低了动脉弹性，与溶剂相比，最大僵硬程度（高应变杨氏模量）增加了900%以上（P<0.05）。这些功能变化与形态学和生化变化相关，表现为胶原含量增加（60%）、弹性蛋白含量减少（74%）以及主动脉壁内弹性膜断裂。此外，与溶剂相比，ANG II处理小鼠的主动脉环对硝普钠的内皮依赖性血管舒张功能受损。因此，目前的数据表明，ANG II以多种方式损伤动脉壁，动脉僵硬可能是ANG II诱导的动脉损伤的常见结果。
