Enhanced vasoconstrictor responses in eNOS deficient mice
Enhanced vasoconstrictor responses in eNOS deficient mice
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DOI：
10.1016/s1089-8603(03)00028-4
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发表时间：
2003-06-01
影响因子：
3.9
通讯作者：
Faraci, F
中科院分区：
文献类型：
--
作者：
Lamping, K;Faraci, F
先前的研究表明，血管收缩是由一氧化氮（NO）调节的。当 NO 合酶 (NOS) 表达或活性长期缺乏时，ET-1 和/或血栓素的收缩可能会增强。 NOS 的多种亚型在血管壁内表达，纯粹的药理学方法无法定义每种亚型的作用。我们通过检查 eNOS-/- 小鼠与野生型 (eNOS+/+) 小鼠主动脉的反应，测试了以下假设：在内皮 NOS (eNOS-/-) 慢性、选择性缺陷的条件下，内皮素-1 (ET-1) 和/或血栓素模拟物 U46619 的血管收缩增强。 ET-1 使 eNOS+/+ 小鼠的主动脉产生剂量依赖性收缩，在用 N-G-硝基-L-精氨酸 (L-NNA) 急性抑制所有 NOS 亚型后，收缩增加两倍。在 eNOS-/- 小鼠中，与 eNOS+/+ 相比，ET-1 的收缩增加两倍。 L-NNA 没有效果。虽然血栓素模拟物 U46619 的主动脉收缩在较低浓度下增加，但在急性抑制 NOS 或 eNOS-/- 小鼠中，U46619 的最大收缩并未增加。这些研究提供了直接证据，表明在 eNOS 缺乏的情况下，ET-1 和血栓素的血管收缩作用增强，表明 eNOS 通常会抑制血管收缩反应。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
Previous studies suggest that vasoconstriction is modulated by nitric oxide (NO). Contractions to ET-1 and/or thromboxane may be enhanced during chronic deficiency in expression or activity of NO synthase (NOS). Multiple isoforms of NOS are expressed within the vessel wall and purely pharmacological approaches cannot define the role of each. We tested the hypothesis that vasoconstriction to endothelin-1 (ET-1) and/or the thromboxane mimetic, U46619, is enhanced under conditions of chronic, selective deficiency in endothelial NOS (eNOS-/-) by examining responses in aorta from eNOS-/- mice compared to wild type (eNOS+/+). ET-1 produced dose-dependent contraction of aorta from eNOS+/+ mice that was increased twofold following acute inhibition of all NOS isoforms with N-G-nitro-L-arginine (L-NNA). In eNOS-/- mice, contractions to ET-1 were increased twofold compared to eNOS+/+. L-NNA had no effect. Although contraction of the aorta to thromboxane mimetic U46619 was increased at lower concentrations, maximal contractions to U46619 were not increased following acute inhibition of NOS or in eNOS-/- mice. These studies provide direct evidence that vasoconstriction to ET-1 and thromboxane is augmented in the face of eNOS deficiency, demonstrating that eNOS normally inhibits vascular contractile responses. (C) 2003 Elsevier Science (USA). All rights reserved.