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硝酸甘油对由U46619(一种血栓素/内过氧化物受体激动剂)引起的血小板聚集的时间依赖性抑制作用。

Time-dependent inhibition by glyceryl trinitrate of platelet aggregation caused by U46619 (a thromboxane/endoperoxide receptor agonist).

作者信息

Kampf G, Ritter J M

机构信息

Department of Clinical Pharmacology, United Medical School, Guy's Hospital, London, United Kingdom.

出版信息

Br J Clin Pharmacol. 1994 Jul;38(1):80-2. doi: 10.1111/j.1365-2125.1994.tb04326.x.

DOI:10.1111/j.1365-2125.1994.tb04326.x
PMID:7946941
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1364842/
Abstract

Glyceryl trinitrate is a weak inhibitor of platelet aggregation in vitro. Its effect on platelet aggregation in response to U46619 (a thromboxane/endoperoxide receptor agonist) was studied turbidometrically in platelet-rich plasma from healthy volunteers. The object was to determine whether inhibition was influenced by a period of preincubation between preparation of platelet-rich plasma and addition of glyceryl trinitrate. Incubation was performed at 37 degrees C and 22 degrees C. Samples were removed at intervals and transferred to an aggregometer cuvette at 37 degrees C. Glyceryl trinitrate (100 microM) or an equal volume of distilled water was added 5 min before U46619 (2 microM), and aggregation recorded as change in light transmission. Inhibition by glyceryl trinitrate was markedly time and temperature dependent, with a progressive increase in inhibitory potency between 120 and 300 min preincubation at 37 degrees C but not at 22 degrees C. The explanation of this is unknown but the effect was not influenced by lipopolysaccharide or by cycloheximide, so it does not appear to be due to exposure to endotoxin or to enzyme induction in vitro.

摘要

硝酸甘油在体外是血小板聚集的弱抑制剂。在来自健康志愿者的富血小板血浆中,采用比浊法研究了其对U46619(一种血栓素/内过氧化物受体激动剂)诱导的血小板聚集的影响。目的是确定在富血小板血浆制备与添加硝酸甘油之间的预孵育时间是否会影响抑制作用。孵育在37℃和22℃下进行。每隔一段时间取出样品,并转移至37℃的血小板聚集仪比色杯中。在加入U46619(2μM)前5分钟加入硝酸甘油(100μM)或等体积的蒸馏水,并将聚集记录为透光率的变化。硝酸甘油的抑制作用明显依赖时间和温度,在37℃预孵育120至300分钟之间抑制效力逐渐增加,但在22℃时则不然。其原因尚不清楚,但该效应不受脂多糖或环己酰亚胺的影响,因此似乎不是由于体外接触内毒素或酶诱导所致。

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本文引用的文献

1
Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets.血小板中内皮源性舒张因子、一氧化氮和前列环素的比较药理学
Br J Pharmacol. 1987 Sep;92(1):181-7. doi: 10.1111/j.1476-5381.1987.tb11310.x.
2
Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase.有机硝酸盐降解过程中一氧化氮生成与鸟苷酸环化酶激活之间的相关性。
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3
N-Acetylcysteine potentiates inhibition of platelet aggregation by nitroglycerin.N-乙酰半胱氨酸增强硝酸甘油对血小板聚集的抑制作用。
J Clin Invest. 1985 Aug;76(2):703-8. doi: 10.1172/JCI112024.
4
Human neutrophils and mononuclear cells inhibit platelet aggregation by releasing a nitric oxide-like factor.人类中性粒细胞和单核细胞通过释放一种一氧化氮样因子来抑制血小板聚集。
Proc Natl Acad Sci U S A. 1989 Aug;86(16):6328-32. doi: 10.1073/pnas.86.16.6328.
5
Human vascular smooth muscle cells inhibit platelet aggregation when incubated with glyceryl trinitrate: evidence for generation of nitric oxide.人血管平滑肌细胞与硝酸甘油一起孵育时可抑制血小板聚集:一氧化氮生成的证据。
Br J Pharmacol. 1991 Apr;102(4):847-50. doi: 10.1111/j.1476-5381.1991.tb12264.x.
6
The metabolism of glyceryl trinitrate to nitric oxide in the macrophage cell line J774 and its induction by Escherichia coli lipopolysaccharide.甘油三硝酸酯在巨噬细胞系J774中代谢为一氧化氮及其受大肠杆菌脂多糖的诱导作用。
Biochem Pharmacol. 1992 Jul 7;44(1):17-24. doi: 10.1016/0006-2952(92)90032-e.
7
Metabolism of glyceryl trinitrate to nitric oxide by endothelial cells and smooth muscle cells and its induction by Escherichia coli lipopolysaccharide.内皮细胞和平滑肌细胞将甘油三硝酸酯代谢为一氧化氮及其受大肠杆菌脂多糖的诱导作用。
Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):982-6. doi: 10.1073/pnas.89.3.982.