诱导型一氧化氮合酶活性在类风湿关节炎患者中增加，并导致内皮功能障碍。

Inducible nitric oxide synthase activity is increased in patients with rheumatoid arthritis and contributes to endothelial dysfunction.

机构信息

Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Box 110, Cambridge, UK.

出版信息

Int J Cardiol. 2008 Oct 13;129(3):399-405. doi: 10.1016/j.ijcard.2008.02.011. Epub 2008 Jun 20.

DOI:10.1016/j.ijcard.2008.02.011

PMID:18571252

Abstract

BACKGROUND

Recent in vitro studies suggest that inducible nitric oxide synthase (iNOS) activity mediates endothelial dysfunction. Rheumatoid arthritis (RA) is a chronic inflammatory condition and is associated with endothelial dysfunction and increased risk of cardiovascular disease. The aim of the study was to establish the contribution of iNOS to endothelial function.

METHODS

Forearm blood flow (FBF) was measured during intra-arterial infusions of acetylcholine (ACh), sodium nitroprusside (SNP), N(G)-monomethyl-l-arginine (l-NMMA) and aminoguanidine (AG) in 12 RA patients and 13 healthy control subjects. Levels of C-reactive protein (CRP) and myeloperoxidase (MPO) were assessed. FBF data are presented as mean percentage changes in the ratio (infused/control arm) of FBF + or - SEM.

RESULTS

FBF response to ACh was reduced in patients with RA compared to controls (179 + or - 29 v. 384 + or - 72%, respectively; P=0.01), but SNP response was not (P=0.5). FBF response to AG differed between patients and controls (-15 + or - 2% v. 13 + or - 4%, respectively; P<0.001), whereas the response to l-NMMA did not (P=0.4). In a multiple regression model log CRP, AG response and LDL were found to be independent predictors of endothelial function (R(2)=0.617, P<0.001).

CONCLUSION

RA patients have endothelial dysfunction and increased iNOS activity in comparison to controls. Furthermore, CRP and iNOS activity were independently associated with endothelial function. Our data demonstrates that inflammation is a key mediator in a process of endothelial dysfunction possibly via activation of iNOS and increased production of MPO.

摘要

背景

最近的体外研究表明，诱导型一氧化氮合酶（iNOS）活性介导内皮功能障碍。类风湿关节炎（RA）是一种慢性炎症性疾病，与内皮功能障碍和心血管疾病风险增加有关。本研究旨在确定 iNOS 对内皮功能的贡献。

方法

在 12 例 RA 患者和 13 例健康对照者的动脉内输注乙酰胆碱（ACh）、硝普钠（SNP）、N（G）-单甲基-L-精氨酸（l-NMMA）和氨基胍（AG）期间，测量前臂血流量（FBF）。评估 C 反应蛋白（CRP）和髓过氧化物酶（MPO）的水平。FBF 数据以 FBF 比值（输注/对照臂）的平均百分比变化呈现+或-SEM。

结果

与对照组相比，RA 患者的 ACh 引起的 FBF 反应降低（179 +或-29 与 384 +或-72%，分别；P=0.01），但 SNP 反应没有差异（P=0.5）。AG 引起的 FBF 反应在患者和对照组之间有所不同（-15 +或-2%与 13 +或-4%，分别；P<0.001），而 l-NMMA 的反应没有差异（P=0.4）。在多元回归模型中，log CRP、AG 反应和 LDL 被发现是内皮功能的独立预测因子（R²=0.617，P<0.001）。