Effects of tumour necrosis factor-α in the human forearm:: blood flow and endothelin-I release

Effects of tumour necrosis factor-α in the human forearm:: blood flow and endothelin-I release
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DOI:
10.1042/cs1030409
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发表时间:
2002-10-01
期刊:
影响因子:
6
通讯作者:
Stehouwer, CDA
Stehouwer, CDA
中科院分区:
医学2区
文献类型:
--
作者:
Patel, JN;Jager, A;Stehouwer, CDA

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肿瘤坏死因子-α(TNF-α)的循环浓度增加见于与血管疾病相关的几种病理状况。TNF-α诱导内皮细胞合成内皮素-1(ET-1),一种有效的血管收缩剂。然而,在败血症中存在深刻的血管舒张,其中ET-1和TNF-α的循环水平升高。ET-1和TNF-α之间相互作用的细节以及健康人体中主要的血液动力学效应尚不清楚。本研究的目的是确定动脉内TNF-α对健康人前臂ET-1溢出、血管张力和内皮功能的影响。肱动脉和深静脉血液样本,前臂血浆流量测量和乙酰胆碱和硝普钠的血流反应,获得在6个健康受试者之前和期间6小时输注TNF-α到肱动脉。暴露于TNF-α时,前臂血流量显著高于基线[中位数(下四分位数,上四分位数):基线,2.6(2.1,2.8)ml.min(-1. 100 ml(-1); TNF-α,4.6(4.5,5.1)ml.min(-1. 100 ml(-1); P
Increased circulating concentrations of tumour necrosis factor-alpha (TNF-alpha) are seen in several pathological conditions associated with vascular disease. TNF-alpha induces the synthesis of endothelin-1 (ET-1), a potent vasoconstictor, by the endothelium. However, there is profound vasodilatation in sepsis, where circulating levels of both ET-1 and TNF-alpha are elevated. The details of the interaction between ET-1 and TNF-alpha and the predominant resulting haemodynamic effect in healthy humans are unclear. The aim of the present study was to determine the effects of intra-arterial TNF-alpha on ET-1 spillover, vascular tone and endothelial function in the healthy human forearm. Brachial arterial and deep venous blood samples, forearm plasma flow measurements and blood flow responses to acetylcholine and sodium nitroprusside were obtained in six healthy subjects before and during a 6 h infusion of TNF-alpha into the brachial artery. Forearm blood flow was significantly greater than baseline during exposure to TNF-alpha [median (lower quartile, upper quartile): baseline, 2.6 (2.1, 2.8) ml.min(-1).100 mi(-1); TNF-alpha, 4.6 (4.5, 5.1) ml.min(-1).100 ml(-1); P