Inducible nitric oxide synthase and vascular reactivity in rat thoracic aorta: effect of aminoguanidine.
Inducible nitric oxide synthase and vascular reactivity in rat thoracic aorta: effect of aminoguanidine.
复制标题
大鼠胸主动脉诱导型一氧化氮合酶和血管反应性：氨基胍的作用。
DOI：
10.1152/jappl.1996.80.1.271
复制
发表时间：
1996
影响因子：
3.3
通讯作者：
David G. McCormack
中科院分区：
文献类型：
--
作者：
Jeremy A. Scott;M. Machoun;David G. McCormack
我们测试了这样的假设：用氨基胍选择性抑制诱导型一氧化氮 (NO) 合酶可以防止暴露于内毒素 [脂多糖 (LPS)] 后血管收缩力的丧失。从 Sprague-Dawley 大鼠身上解剖主动脉环，悬浮在含有克雷布斯溶液的器官浴中，并测试血管反应性。用 LPS（1 微克/毫升）孵育 5 小时的血管表现出对去氧肾上腺素的最大收缩反应显着降低。氨基胍 (100 microM) 将 LPS 处理的血管的最大收缩反应恢复到对照血管的水平。氨基胍在抑制血管组织中组成型 NO 合酶方面的效力比 NG-硝基-L-精氨酸甲酯大约低 250 倍，这取决于其进一步增加次最大收缩主动脉环张力的能力。在有和没有LPS 孵育的血管组织中测定NO 合酶活性。与对照容器相比，用 LPS 孵育的容器表现出诱导型 NO 合酶活性水平显着增加。当组织匀浆与氨基胍一起孵育时，这种增加恢复到对照水平。我们得出结论，氨基胍是诱导型 NO 合酶的选择性浓度依赖性抑制剂，可能是评估诱导型 NO 合酶在内毒素血症和脓毒症异常血管收缩特征中的作用的有用探针。
We tested the hypothesis that selective inhibition of the inducible form of nitric oxide (NO) synthase with aminoguanidine would prevent the loss of vascular contractility after exposure to endotoxin [lipopolysaccharide (LPS)]. Aortic rings were dissected from Sprague-Dawley rats, suspended in organ baths containing Krebs solution, and tested for vascular reactivity. Vessels incubated with LPS (1 microgram/ml) for 5 h exhibited a significant decrease in the maximal contractile response to phenylephrine. Aminoguanidine (100 microM) restored the maximal contractile response of LPS-treated vessels to the level of the control vessels. Aminoguanidine was approximately 250-fold less potent than NG-nitro-L-arginine methyl ester in inhibiting the constitutive NO synthase in vascular tissue as determined by its ability to further increase tone of submaximally contracted aortic rings. NO synthase activity was determined in vascular tissue incubated with and without LPS. Vessels incubated with LPS exhibited a marked increase in the levels of inducible NO synthase activity compared with control vessels. This increase was restored to control levels when tissue homogenates were incubated with aminoguanidine. We conclude that aminoguanidine is a selective concentration-dependent inhibitor of the inducible form of NO synthase and may be a useful probe to evaluate the role of inducible NO synthase in the abnormal vascular contractility characteristic of endotoxemia and sepsis.