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通过亚硝酰氯钌的闪光光解测定一氧化氮介导的血管平滑肌舒张的效能和动力学。

Potency and kinetics of nitric oxide-mediated vascular smooth muscle relaxation determined with flash photolysis of ruthenium nitrosyl chlorides.

作者信息

Carter T D, Bettache N, Ogden D

机构信息

National Institute for Medical Research, London.

出版信息

Br J Pharmacol. 1997 Nov;122(6):971-3. doi: 10.1038/sj.bjp.0701549.

DOI:10.1038/sj.bjp.0701549
PMID:9401757
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565063/
Abstract

Flash photolysis of thermally stable, photolabile 'caged' precursors permits rapid and precise changes of ligand concentration at their site of action. This approach was used to determine the concentration-dependence and time course of NO-mediated relaxation of aortic smooth muscle, by use of two photolabile NO donors, trichloronitrosylruthenium (Ru(NO)Cl3) and dipotassium pentachloronitrosylruthenate (K2Ru(NO)Cl5). At concentrations up to 500 microM, both compounds were non-toxic before photolysis, and produced non-toxic by-products on photolysis. Photolytic release of NO produced relaxations of intact and endothelium-denuded aortic rings precontracted with noradrenaline (0.1-0.5 microM), with an EC50 for NO-mediated relaxations of 10.5 nM and 13 nM, respectively. NO-mediated relaxations were reversibly blocked by 1 microM oxyhaemoglobin. The time course of NO-mediated relaxation comprised a delay of 3-7 s, followed by a sigmoidal decline in tension with peak rates that were strongly dependent on NO concentration.

摘要

对热稳定、光不稳定的“笼形”前体进行闪光光解,可以在其作用位点快速且精确地改变配体浓度。通过使用两种光不稳定的一氧化氮供体,即三氯亚硝酰钌(Ru(NO)Cl3)和五氯亚硝酰钌酸钾(K2Ru(NO)Cl5),采用这种方法来确定一氧化氮介导的主动脉平滑肌舒张的浓度依赖性和时间进程。在浓度高达500微摩尔时,两种化合物在光解前均无毒,且光解时产生无毒副产物。一氧化氮的光解释放使预先用去甲肾上腺素(0.1 - 0.5微摩尔)预收缩的完整和内皮剥脱的主动脉环舒张,一氧化氮介导舒张的半数有效浓度(EC50)分别为10.5纳摩尔和13纳摩尔。1微摩尔氧合血红蛋白可可逆地阻断一氧化氮介导的舒张。一氧化氮介导舒张的时间进程包括3 - 7秒的延迟,随后张力呈S形下降,峰值速率强烈依赖于一氧化氮浓度。

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