Role of the nitric oxide metabolic pathway and prostanoids in the pathogenesis of endothelial dysfunction and essential hypertension in young men
Role of the nitric oxide metabolic pathway and prostanoids in the pathogenesis of endothelial dysfunction and essential hypertension in young men
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DOI：
10.1038/hr.2010.169
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发表时间：
2011-01-01
影响因子：
5.4
通讯作者：
Szuba, Andrzej
中科院分区：
文献类型：
--
作者：
Doroszko, Adrian;Andrzejak, Ryszard;Szuba, Andrzej
本研究的目的是探讨选择性前列腺素和一氧化氮(NO)代谢途径在伴有和不伴有高血压(HTN)的青年男性内皮功能障碍(ED)发病机制中的作用。研究对象为70名18~40岁的男性，其中高血压23人，正常血压47人。测定NO途径的初始代谢物浓度(不对称二甲基精氨酸、L-精氨酸和对称性二甲基精氨酸)、心血管危险标志物(血脂、肌酐、血糖和高敏C反应蛋白)、氧化应激标志物(丙二醛、硫醇指数和硝基酪氨酸)和前列腺素(血栓素B2和6-酮-前列腺素F(PGF)-1-α)。观察静脉注射L精氨酸(16.0g)前后血管内皮功能(血流介导血管扩张)的超声变化。口服吲哚美辛(75 mg/d)2天后重复所有测量。高血压组和正常血压组的ED患病率相似。高血压组基线血浆6-keto-PGF-1-α水平较低，TxB2基线水平较高。用前列腺素水平评估吲哚美辛的反应是不同的，并且依赖于HTN的存在。无论是在基线还是在消炎痛治疗后，都没有观察到NO途径的代谢物有显著差异。在高血压患者中，L精氨酸和消炎痛对FMD有协同作用。血压正常的年轻男性的ED主要依赖于无缺乏症。在年轻的高血压男性中，前列腺素代谢紊乱在降低NO的生物利用度方面起着重要作用。ED在潜在健康人群中的高患病率表明超声FMD测量在心血管危险分层中是一个重要的工具。高血压研究(2011年)34期，79-86期；DOI：10.1038/hr.2010.169；2010年10月7日在线发表
The aim of this study was to explore the role of selected prostanoids and the nitric oxide (NO) metabolic pathway in the pathogenesis of endothelial dysfunction (ED) in young men with and without essential hypertension (HTN). A total of 70 men aged 18-40 years old (23 hypertensive and 47 normotensive) were investigated. Initial metabolite concentrations of the NO pathway (asymmetric dimethylarginine, L-arginine and symmetric dimethylarginine), selected cardiovascular risk markers (serum lipids, creatinine, glucose and high-sensitivity C-reactive protein), oxidative stress markers (malonylodialdehyde, thiol index and nitrotyrosine) and prostanoids (thromboxane B2 (TxB2) and 6-keto-prostaglandin F (PGF)-1-alpha) were measured. Ultrasound assessment of endothelial function (flow-mediated vasodilation (FMD)) of the brachial artery was studied before and after intravenous infusion of L-arginine (16.0 g). All measurements were repeated after oral administration of indomethacin (75mg per day) for 2 days. The prevalence of ED was similar in both hypertensive and normotensive groups. A lower baseline plasma level of 6-keto-PGF-1-alpha and a higher baseline of TxB2 were observed in the hypertensive group. A different response to indomethacin assessed by prostanoid levels was observed and was dependent on the presence of HTN. No significant differences in metabolites of the NO pathway were observed at either baseline or following indomethacin treatment. In hypertensive patients, L-arginine and indomethacin had a synergistic positive effect on FMD. ED in young normotensive men primarily depends on NO deficiency. In young hypertensive men, disorders in prostanoid metabolism have important roles in decreasing NO bioavailability. The high prevalence of ED in potentially healthy subjects suggests that the ultrasound FMD measurement is an important tool in the stratification of cardiovascular risk. Hypertension Research (2011) 34, 79-86; doi: 10.1038/hr.2010.169; published online 7 October 2010