Amlodipine reduces AngII-induced aortic aneurysms and atherosclerosis in hypercholesterolemic mice.
Amlodipine reduces AngII-induced aortic aneurysms and atherosclerosis in hypercholesterolemic mice.
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DOI：
10.1371/journal.pone.0081743
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Daugherty A
中科院分区：
文献类型：
--
作者：
Chen X;Rateri DL;Howatt DA;Balakrishnan A;Moorleghen JJ;Morris AJ;Charnigo R;Cassis LA;Daugherty A
本研究的目的是确定二氢吡啶类钙通道阻滞剂对血管紧张素II（AngII）诱导的血管病变的影响。通过渗透泵向雄性LDL受体-/-小鼠输注载体、Ang II（5 mg/kg/d）、AngII（1，000 ng/kg/min）或AngII + Ang II 4周（n=10/组）。在泵植入前1周和输注4周期间，给小鼠喂食富含饱和脂肪的饮食。生理盐水+Ang Ⅱ组和Ang Ⅱ + Ang Ⅱ组小鼠输注Ang Ⅱ后血浆浓度分别为32 ± 2 ng/ml和27 ± 2 ng/ml。这一输注速率并不影响AngII诱导的收缩压升高。10只输注AngII的小鼠中有3只（30%）死于主动脉破裂，而在共输注AngII + AngII的小鼠中没有发生主动脉破裂。测量肾上主动脉宽度和升主动脉内膜面积以确定主动脉瘤。在不输注AngII的情况下，血管紧张素转换酶不改变肾上主动脉宽度和升主动脉面积。AngII的输注导致肾上主动脉宽度显著增加（生理盐水+赋形剂vs AngII +赋形剂：0.86 ± 0.02 vs 1.72 ± 0.26 mm; P=0.0006），而AngII和血管紧张素II的共输注减少了腹部扩张（1.02 ± 0.14 mm; P=0.003）。正如预期的那样，AngII输注增加了升主动脉的平均内膜面积（生理盐水+溶媒vs AngII +溶媒：8.5 ± 0.3 vs 12.5 ± 1.1 mm 2; P=0.001），而AngII和血管生成素联合输注可消融升主动脉的扩张（8.6 ± 0.2 mm 2; P=0.03）。共同施用Ang II还显著减弱了胸部区域中AngII诱导的动脉粥样硬化，如通过病变面积百分比量化的（AngII +媒介物对AngII +赋形剂：5.8 ± 2.1%对0.3 ± 0.1%; P=0.05）。Amplitude抑制AngII诱导的腹主动脉瘤和升主动脉瘤，以及高胆固醇血症小鼠的动脉粥样硬化。
The purpose of this study was to determine effects of amlodipine, a dihydropyridine calcium channel blocker, on development of angiotensin II (AngII)-induced vascular pathologies. Male LDL receptor -/- mice were infused with vehicle, amlodipine (5 mg/kg/d), AngII (1,000 ng/kg/min), or AngII + amlodipine for 4 weeks through osmotic pumps (n=10/group). Mice were fed a saturated fat-enriched diet for 1 week prior to pump implantation and during 4 weeks of infusion. Infusion of amlodipine resulted in plasma concentrations of 32 ± 2 ng/ml and 27 ± 2 ng/ml for mice in saline + amlodipine and AngII + amlodipine groups, respectively. This infusion rate of amlodipine did not affect AngII-induced increases in systolic blood pressure. Three of 10 (30%) mice infused with AngII died of aortic rupture, while aortic rupture did not occur in mice co-infused with AngII + amlodipine. Suprarenal aortic width and intimal area of ascending aortas were measured to define aortic aneurysms. In the absence of AngII infusion, amlodipine did not change suprarenal aortic width and ascending aortic area. Infusion of AngII led to profound increases of suprarenal aortic width (saline + vehicle versus AngII + vehicle: 0.86 ± 0.02 versus 1.72 ± 0.26 mm; P=0.0006), whereas co-infusion of AngII and amlodipine diminished abdominal dilation (1.02 ± 0.14 mm; P=0.003). As expected, AngII infusion increased mean intimal area of ascending aortas (saline + vehicle versus AngII + vehicle: 8.5 ± 0.3 versus 12.5 ± 1.1 mm2; P=0.001), while co-infusion of AngII and amlodipine ablated dilation of the ascending aorta (8.6 ± 0.2 mm2; P=0.03). Co-administration of amlodipine also significantly attenuated AngII-induced atherosclerosis in the thoracic region as quantified by percent lesion area (AngII + vehicle versus AngII + amlodipine: 5.8 ± 2.1 % versus 0.3 ± 0.1%; P=0.05). Amlodipine inhibited AngII-induced aortic aneurysms in both the abdominal and ascending regions, and atherosclerosis in hypercholesterolemic mice.
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DOI：
10.1042/cs20090372
发表时间：
2010-03-09
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Daugherty A;Rateri DL;Charo IF;Owens AP;Howatt DA;Cassis LA
通讯作者：
Cassis LA
影响因子：
20.1
作者：
Das R;Burke T;Van Wagoner DR;Plow EF
通讯作者：
Plow EF
影响因子：
5.3
作者：
Doran, Derek E.;Weiss, Daiana;Taylor, W. Robert
通讯作者：
Taylor, W. Robert
DOI：
10.3791/1291
发表时间：
2009-05-15
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Daugherty, Alan;Rateri, Debra;Balakrishnan, Anju
通讯作者：
Balakrishnan, Anju
影响因子：
8.7
作者：
Alcorn, HG;Wolfson, SK;OLeary, D
通讯作者：
OLeary, D