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Nω-硝基-L-精氨酸苄酯,一种强效的内皮依赖性舒张不可逆抑制剂。

NW-nitro L-arginine benzyl ester, a potent irreversible inhibitor of endothelium dependent relaxation.

作者信息

Thomas G, Ramwell P W

机构信息

Department of Physiology and Biophysics, Georgetown University Medical Center, NW Washington, DC 20007.

出版信息

Biochem Biophys Res Commun. 1991 Sep 30;179(3):1677-82. doi: 10.1016/0006-291x(91)91768-8.

DOI:10.1016/0006-291x(91)91768-8
PMID:1930206
Abstract

In the rat aorta preparation, we have used the nitro-arginine derivative, NW-nitro L-arginine benzyl ester (NABE), as a probe to investigate the relationship between L-arginine and the endothelium derived relaxing factor (EDRF). We find NABE to be a potent endothelium dependent vasoconstrictor and inhibitor of relaxation. The effect of NABE is irreversible and not removed by subsequent washing. The vasoconstrictor effect of NABE differs from other EDRF inhibitors like NG-monomethyl L-arginine (L-NMMA) in that it is not antagonized by pre-treatment with excess L-arginine. In contrast, like other EDRF inhibitors, at high concentration NABE exhibits vasodilation which is antagonized by methylene blue. We suggest that the previous reports on the antagonism between L-arginine and the putative EDRF inhibitors like L-NMMA are due to their structural similarities rather than to externally added L-arginine acting as a substrate for EDRF synthesis.

摘要

在大鼠主动脉制备实验中,我们使用了硝基精氨酸衍生物,Nω-硝基-L-精氨酸苄酯(NABE),作为一种探针来研究L-精氨酸与内皮衍生舒张因子(EDRF)之间的关系。我们发现NABE是一种强效的内皮依赖性血管收缩剂和舒张抑制剂。NABE的作用是不可逆的,后续冲洗无法消除。NABE的血管收缩作用与其他EDRF抑制剂如Nω-单甲基-L-精氨酸(L-NMMA)不同,因为预先用过量的L-精氨酸处理并不能拮抗它的作用。相反,与其他EDRF抑制剂一样,高浓度的NABE会表现出血管舒张作用,而亚甲蓝可拮抗这种作用。我们认为,先前关于L-精氨酸与L-NMMA等假定的EDRF抑制剂之间拮抗作用的报道,是由于它们的结构相似性,而不是因为外部添加的L-精氨酸作为EDRF合成的底物。

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