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过氧亚硝酸盐而非一氧化氮供体可破坏肾上腺素:高效液相色谱测定及大鼠主动脉收缩性

Peroxynitrite but not nitric oxide donors destroys epinephrine: HPLC measurement and rat aorta contractility.

作者信息

Shelkovnikov Stanislav, Gonick Harvey C

机构信息

Nephrology Section, Medical and Research Services, Veteran Affairs Greater, Los Angeles Healthcare System at West Los Angeles, Los Angeles, CA 90073, USA.

出版信息

Life Sci. 2004 Oct 22;75(23):2765-73. doi: 10.1016/j.lfs.2004.04.044.

Abstract

Nitric oxide (NO) and peroxynitrite (ONOO) have been reported to destroy catecholamines. We compared the ability of NO donors and peroxynitrite to decompose epinephrine in both chemical and pharmacological experiments. Epinephrine (1 microM) was incubated with NO donors (SNAP and MAHMA NONOate) and ONOO at a concentration of 0.1 mM in phosphate buffer (pH 7.4; 0.1 M) or Krebs solution for 10 minutes at 37 degrees C. HPLC revealed that the concentration of epinephrine in the presence of NO donors was unaltered. In contrast, peroxynitrite decreased epinephrine concentration more than 20 fold. Similar relationships were obtained in the study of rat thoracic aorta ring contraction. The contractile activity (EC50) of epinephrine in control solutions and after incubation of NE with NO donors did not change. EC50 was measured at 8-10 nM in control solutions and after preincubation with NO donors. However when epinephrine was preincubated with peroxynitrite, no contractile effect was evoked. Therefore, under these experimental conditions peroxynitrite, but not NO donors, was capable of destroying epinephrine.

摘要

据报道,一氧化氮(NO)和过氧亚硝酸盐(ONOO)会破坏儿茶酚胺。我们在化学和药理学实验中比较了NO供体和过氧亚硝酸盐分解肾上腺素的能力。将肾上腺素(1微摩尔)与NO供体(S-亚硝基-N-乙酰青霉胺和N-甲基-D-精氨酸硝普钠)以及浓度为0.1毫摩尔的过氧亚硝酸盐在磷酸盐缓冲液(pH 7.4;0.1摩尔)或 Krebs 溶液中于37℃孵育10分钟。高效液相色谱显示,在NO供体存在的情况下,肾上腺素的浓度未发生变化。相比之下,过氧亚硝酸盐使肾上腺素浓度降低了20倍以上。在大鼠胸主动脉环收缩研究中也得到了类似的结果。在对照溶液中以及NE与NO供体孵育后,肾上腺素的收缩活性(半数有效浓度)没有变化。在对照溶液中以及与NO供体预孵育后,半数有效浓度测定为8 - 10纳摩尔。然而,当肾上腺素与过氧亚硝酸盐预孵育时,未引发收缩效应。因此,在这些实验条件下,过氧亚硝酸盐而非NO供体能够破坏肾上腺素。

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