Assessment of vascular function in systemic sclerosis -: Indications of the development of nitrate tolerance as a result of enhanced endothelial nitric oxide production
Assessment of vascular function in systemic sclerosis -: Indications of the development of nitrate tolerance as a result of enhanced endothelial nitric oxide production
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DOI：
10.1002/art.10191
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发表时间：
2002-05-01
影响因子：
--
通讯作者：
Caidahl, K
中科院分区：
文献类型：
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作者：
Andersen, G;Mincheva-Nilsson, L;Caidahl, K
Objective.目的探讨系统性硬化症（SSc）患者内皮依赖性和非内皮依赖性功能与血管僵硬度及内皮活化标志物水平的关系。内皮依赖性（即，流动介导的）和内皮非依赖性的（即，硝酸甘油诱导的）肱动脉的扩张通过高分辨率超声成像测量为24名SSc患者和24名年龄和性别匹配的健康对照的从基线变化的百分比（分别为FMD%和NTG%）。每单位时间收缩压的最大增加（dP/dt（max）），作为动脉壁硬度的测量，通过脉冲压平眼压计在桡动脉中进行评估。血浆硝酸盐，一氧化氮的最重要的代谢产物，和24小时尿排泄的硝酸盐测定气相色谱质谱法。采用酶联免疫吸附法测定血清可溶性E-选择素和可溶性血管细胞粘附分子1（sVCAM-1）的含量。肱动脉FMD%和NTG%在SSc患者和对照组之间没有差异。患者桡动脉dP/dt（max）显著增加，并与血浆硝酸盐和sVCAM-1水平升高显著相关。24小时尿硝酸盐排泄量有升高的趋势。肱动脉NTG%与血浆硝酸盐和可溶性内皮细胞粘附分子水平呈显著负相关。SSc保留了肱动脉对充血和硝酸甘油刺激的扩张能力。然而，桡动脉的硬度增加。内皮活化似乎决定了肱动脉NTG%和桡动脉dP/dt（max）的程度。这些数据与硝酸盐耐受性存在于SSc肱动脉壁的血管平滑肌细胞中的假设是一致的。
Objective. To investigate the relationship between endothelium-dependent and endothelium-independent functions and the stiffness of conduit arteries as well as levels of endothelial activation markers in patients with systemic sclerosis (SSc).Methods. Endothelium-dependent (i.e., flowmediated) and endothelium-independent (i.e., nitroglycerin-induced) dilation of the brachial artery was measured as the percentage of change from baseline (FMD% and NTG%, respectively) in 24 SSc patients and 24 age- and sex-matched healthy controls by high-resolution ultrasound imaging. The maximum increase in systolic pressure per unit of time (dP/dt(max)), as a measure of arterial wall stiffness, was assessed in the radial artery by pulse applanation tonometry. Plasma nitrate, the most important metabolite of nitric oxide, and 24-hour urinary excretion of nitrate were measured by gas chromatography mass spectrometry. Soluble E-selectin and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay.Results. Brachial artery FMD% and NTG% did not differ between SSc patients and controls. Radial artery dP/dt(max) was significantly increased in the patients and correlated significantly with elevated levels of plasma nitrate and sVCAM-1. Twenty-four-hour urinary nitrate excretion tended to be elevated. Brachial artery NTG% was significantly inversely correlated with levels of plasma nitrate and soluble endothelial adhesion molecules.Conclusion. The ability of the brachial arteries to dilate in response to hyperemia and nitroglycerin challenge is preserved in SSc. Stiffness of the radial artery is increased, however. Endothelial activation seems to determine the extent of the brachial artery NTG% and the radial artery dP/dt(max). The data are compatible with the hypothesis that nitrate tolerance is present in the vascular smooth muscle cells of the brachial artery wall in SSc.