Division of Cardiology, Department of Medicine, University Health Network and Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Can J Physiol Pharmacol. 2009 Jun;87(6):455-9. doi: 10.1139/y09-030.
Continuous exposure to nitroglycerin (GTN) results in development of tolerance and is associated with increased free radical production and abnormal endothelial function. Elevated plasma biomarkers of inflammation have been shown to be associated with endothelial dysfunction in most cardiovascular conditions. It remains unclear whether exposure to GTN is also associated with increased biomarkers of endothelial and vascular injury or vascular inflammation. In an investigator-blind study, a total of 28 healthy volunteers were randomized to continuous therapy with GTN (0.6 mg/h 24 h/day for 7 days) or no therapy. Venous blood was collected on day 0 and day 7. Plasma levels of markers such as asymmetric dimethyl-arginine (ADMA), human soluble P-selectin, interleukin-6, tumor necrosis factor-alpha, intercellular adhesion molecule-1, and oxidized low-density lipoproteins were measured. The levels of blood markers on day 0 were similar in the control and GTN-treated groups. After 7 days of GTN exposure, there were no significant changes in the different markers of vascular inflammation and injury either in the GTN or control group (all p > 0.5). The present study documents that prolonged continuous therapy with transdermal GTN therapy is not associated with changes in markers of vascular inflammation and injury.
持续接触硝化甘油(GTN)会导致耐受性的产生,并且与自由基产生增加和内皮功能异常有关。在大多数心血管疾病中,升高的炎症血浆生物标志物已被证明与内皮功能障碍有关。目前尚不清楚接触 GTN 是否也与内皮和血管损伤或血管炎症的生物标志物增加有关。在一项研究者盲法研究中,共 28 名健康志愿者被随机分为 GTN 持续治疗组(24 小时/天,0.6 毫克/小时,持续 7 天)或无治疗组。在第 0 天和第 7 天采集静脉血。测量了不对称二甲基精氨酸(ADMA)、人可溶性 P 选择素、白细胞介素 6、肿瘤坏死因子-α、细胞间黏附分子 1 和氧化型低密度脂蛋白等标志物的血浆水平。在对照组和 GTN 治疗组中,第 0 天的血液标志物水平相似。在 GTN 暴露 7 天后,GTN 组和对照组的血管炎症和损伤的不同标志物均无明显变化(均 P > 0.5)。本研究表明,经皮 GTN 治疗的长期持续治疗与血管炎症和损伤标志物的变化无关。