Impairment of endothelium-dependent relaxation of aortas and pulmonary arteries from spontaneously hyperlipidemic mice (Apodemus sylvaticus)

Impairment of endothelium-dependent relaxation of aortas and pulmonary arteries from spontaneously hyperlipidemic mice (Apodemus sylvaticus)
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DOI:
10.1016/j.vph.2007.06.001
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发表时间:
2007-08-01
影响因子:
4
通讯作者:
Ito, Katsuaki
Ito, Katsuaki
中科院分区:
医学2区
文献类型:
--
作者:
Ito, Kaoru M.;Okayasu, Misao;Ito, Katsuaki

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我们评估了欧洲森林鼠(Apodemus sylvaticus)的胸主动脉和肺动脉的内皮功能,表现出高胆固醇血症。根据血浆胆固醇水平将小鼠分为高胆固醇血症组(阿勒,血浆总胆固醇200-300 mg/dl)和正常胆固醇血症组(ANL,血浆总胆固醇< 200 mg/dl)。乙酰胆碱(ACh)引起内皮依赖性舒张预收缩的肺动脉和肺动脉。肺动脉的舒张完全依赖于一氧化氮。这种舒张在阿勒肺动脉中被抑制。另一方面,部分乙酰胆碱诱导的胸主动脉舒张对N-ω-硝基-L-精氨酸(L-NNA)有抗性。L-NNA敏感性和抗ACh舒张也被抑制在阿勒大鼠。血管内皮依赖性舒张的抑制与血浆总胆固醇水平相关。阿勒和ANL小鼠肺动脉对硝普钠(SNP)的内皮非依赖性舒张相似,但阿勒小鼠胸主动脉对SNP的敏感性略有下降,对SNP的最大反应没有变化。在阿勒和ANL小鼠的肺动脉和肺动脉中未观察到形态学变化。因此,阿勒小鼠作为一种新的实验模型,研究高脂血症与血管疾病的关系,因为在这些轻度高脂血症动物内皮功能受损。(C)2007爱思唯尔公司All rights reserved.
We evaluated the endothelial function of thoracic aortas and pulmonary arteries in a population of European wood mice (Apodemus sylvaticus), which exhibit hypercholesterolemia. According to the plasma cholesterol level, mice were divided into two groups: hypercholesterolemic (AHL, total plasma cholesterol 200-300 mg/dl) and normocholesterolemic (ANL, total plasma cholesterol < 200 mg/dl). Acetylcholine (ACh) caused endothelium-dependent relaxation of precontracted aortas and pulmonary arteries. Relaxation of the pulmonary artery is completely dependent on nitric oxide. This relaxation was inhibited in AHL pulmonary arteries. On the other hand, part of the ACh-induced relaxation of the thoracic aorta was resistant to N-omega-nitro-L-arginine (L-NNA). L-NNA-sensitive and -resistant relaxation to ACh were also inhibited in AHL aortas. Inhibition of endothelium-dependent relaxation of the aortas was correlated with total plasma cholesterol level. Endothelium-independent relaxation to sodium nitroprusside (SNP) was similar in AHL and ANL pulmonary arteries, but in the thoracic aorta of AHL mice, the sensitivity to SNP was slightly decreased, without a change in maximal response to SNP. No morphological change was observed in the aortas and the pulmonary arteries from AHL and ANL mice. Thus, AHL mice are valuable as a new experimental model to study the relation of hyperlipidemia to vascular disease since the endothelial function is impaired in these mild hyperlipidemic animals. (C) 2007 Elsevier Inc. All rights reserved.