ANG II infusion promotes abdominal aortic aneurysms independent of increased blood pressure in hypercholesterolemic mice
ANG II infusion promotes abdominal aortic aneurysms independent of increased blood pressure in hypercholesterolemic mice
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DOI：
10.1152/ajpheart.00028.2009
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发表时间：
2009-05-01
影响因子：
4.8
通讯作者：
Daugherty, Alan
中科院分区：
文献类型：
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作者：
Cassis, Lisa A.;Gupte, Manisha;Daugherty, Alan
[10] Czetella，Gupte M，Thayer S，Zhang X，Charnigo R，Howatt DA，Rateri DL，Daughtera A.血管紧张素II输注促进高胆固醇血症小鼠的腹主动脉瘤，与血压升高无关。Am J Physiol Heart Circ Physiol 296：H1660-H1665，2009.首次发表于2009年2月27日; doi：10.1152/ajpheart.00028.2009。血管紧张素II在高血压小鼠中的输注增加动脉粥样硬化并导致腹主动脉瘤（AAA）的形成。本研究的目的是确定血管紧张素II诱导的高血压对这些血管病变的贡献。雄性载脂蛋白E（apoE）和LDL受体（LDLr）缺陷小鼠输注ANG II（1，000 ng.kg（-1）.min（-1））或去甲肾上腺素（NE; 5.6 mg.kg（-1）.day（-1））28天。输注ANG II或NE使平均动脉压（MAP; ANG II，133 +/- 2.8; NE，129 +/- 13 mmHg）升高的程度与基线血压（MAP，107 +/- 2 mmHg）相似。输注ANG II的apoE缺陷（apoE（-/-））或LDLr缺陷（LDLr（-/-））小鼠的腹主动脉宽度均增加（apoE（-/-）：1.4 +/- 0.1; LDLr（-/-）：1.6 +/- 0.2 mm）。与此相反，NE没有改变腹主动脉瘤的直径（apoE（-/-）：0.91 +/- 0.03; LDLr（-/-）：0.87 +/- 0.02 mm）。同样，与NE相比，输注ANG II的小鼠主动脉弓中的动脉粥样硬化病变更大。在ANG II的降压输注速率（500 ng.kg（-1）.min（-1））下，50%的apoE（-/-）小鼠出现AAA。或者，给予ANG II输注apoE（-/-）小鼠肼苯哒嗪（250 mg/l）（1，000 ng.kg（-1）.min（-1））降低收缩压（第28天：ANG II，157 +/- 6; ANG II/肼苯哒嗪，135 +/- 6 mmHg），但不能预防AAA形成或动脉粥样硬化。这些结果表明，血管紧张素II的高血压小鼠的输液诱导AAAs和增加动脉粥样硬化独立于血压升高。
Cassis LA, Gupte M, Thayer S, Zhang X, Charnigo R, Howatt DA, Rateri DL, Daugherty A. ANG II infusion promotes abdominal aortic aneurysms independent of increased blood pressure in hypercholesterolemic mice. Am J Physiol Heart Circ Physiol 296: H1660-H1665, 2009. First published February 27, 2009; doi:10.1152/ajpheart.00028.2009.-Infusion of ANG II in hyperlipidemic mice augments atherosclerosis and causes formation of abdominal aortic aneurysms (AAAs). The purpose of this study was to define the contribution of ANG II-induced hypertension to these vascular pathologies. Male apolipoprotein E (apoE)-and LDL receptor (LDLr)-deficient mice were infused with ANG II (1,000 ng.kg(-1).min(-1)) or norepinephrine (NE; 5.6 mg.kg(-1).day(-1)) for 28 days. Infusion of ANG II or NE increased mean arterial pressure (MAP; ANG II, 133 +/- 2.8; NE, 129 +/- 13 mmHg) to a similar extent compared with baseline blood pressures (MAP, 107 +/- 2 mmHg). Abdominal aortic width increased in both apoE-deficient (apoE(-/-)) or LDLr-deficient (LDLr(-/-)) mice infused with ANG II (apoE(-/-): 1.4 +/- 0.1; LDLr(-/-): 1.6 +/- 0.2 mm). In contrast, NE did not change diameters of abdominal aortas (apoE(-/-): 0.91 +/- 0.03; LDLr(-/-): 0.87 +/- 0.02 mm). Similarly, atherosclerotic lesions in aortic arches were much greater in mice infused with ANG II compared with NE. At a subpressor infusion rate of ANG II (500 ng.kg(-1).min(-1)), AAAs developed in 50% of apoE(-/-) mice. Alternatively, administration of hydralazine (250 mg/l) to ANG II-infused apoE(-/-) mice (1,000 ng.kg(-1).min(-1)) lowered systolic blood pressure (day 28: ANG II, 157 +/- 6; ANG II/hydralazine, 135 +/- 6 mmHg) but did not prevent AAA formation or atherosclerosis. These results demonstrate that infusion of ANG II to hyperlipidemic mice induces AAAs and augments atherosclerosis independent of increased blood pressure.