Angiotensin-converting enzyme inhibitors attenuate propofol-induced pro-oxidative and antifibrinolytic effect in human endothelial cells.

Angiotensin-converting enzyme inhibitors attenuate propofol-induced pro-oxidative and antifibrinolytic effect in human endothelial cells.
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DOI:
10.1177/1470320316687197
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发表时间:
2017-01
期刊:
Journal of the renin-angiotensin-aldosterone system : JRAAS
影响因子:
--
通讯作者:
Chabielska E
Chabielska E
中科院分区:
其他
文献类型:
--
作者:
Wojewodzka-Zelezniakowicz M;Gromotowicz-Poplawska A;Kisiel W;Konarzewska E;Szemraj J;Ladny JR;Chabielska E

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本研究旨在观察血浆和组织血管紧张素转换酶抑制剂(ACE-IS)对异丙酚诱导的血管内皮细胞功能障碍的影响,并探讨其作用机制。我们观察了异丙酚(50μM)、奎那普利拉和依那普利拉(10−5 M)对人脐静脉内皮细胞纤溶活性(t-PA、PAI-1、TAFI抗原水平)、氧化应激参数(H_2O_2和丙二醛抗原水平、超氧化物歧化酶和NADPH氧化酶基因水平)和一氧化氮生物利用度(NO_2/NO_3浓度和一氧化氮合酶基因表达水平)的影响。我们发现,在体外,两种ACE-IS都能促进相似的内皮纤溶特性,并降低氧化应激。单用异丙酚可增加血管内皮细胞释放抗纤溶因子和促氧化因子,并增加iNOS的表达。我们还发现,在ACE-IS预孵育后,异丙酚与HUVECs共同孵育会导致异丙酚的抗纤溶和促氧化作用减弱,这一作用在ACE-IS预孵育后相似。这一观察结果表明,所研究的ACE-IS对异丙酚引起的内皮细胞功能障碍具有保护作用,而不依赖于血流动力学。
The aim of this study was to investigate the effects of plasma and tissue angiotensin-converting enzyme inhibitors (ACE-Is) against propofol-induced endothelial dysfunction and to elucidate the involved mechanisms in vitro. We examined the effects of propofol (50 μM), quinaprilat and enalaprilat (10−5 M) on fibrinolysis (t-PA, PAI-1, TAFI antigen levels), oxidative stress parameters (H2O2 and MDA antigen levels and SOD and NADPH oxidase mRNA levels) and nitric oxide bioavailability (NO2/NO3 concentration and NOS expression at the level of mRNA) in human umbilical vein endothelial cells (HUVECs). We found that both ACE-Is promoted similar endothelial fibrinolytic properties and decreased oxidative stress in vitro. Propofol alone increased the release of antifibrinolytic and pro-oxidative factors from the endothelium and increased mRNA iNOS expression. We also found that the incubation of HUVECs in the presence of propofol following ACE-Is pre-incubation caused weakness of the antifibrinolytic and pro-oxidative potential of propofol and this effect was similar after both ACE-Is. This observation suggests that the studied ACE-Is exerted protective effects against endothelial cell dysfunction caused by propofol, independently of hemodynamics.
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