Differential effects of pentaerythritol tetranitrate and nitroglycerin on the development of tolerance and evidence of lipid peroxidation: A human in vivo study
Differential effects of pentaerythritol tetranitrate and nitroglycerin on the development of tolerance and evidence of lipid peroxidation: A human in vivo study
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DOI：
10.1016/s0735-1097(01)01414-0
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发表时间：
2001-09-01
影响因子：
24
通讯作者：
Parker, JD
中科院分区：
文献类型：
--
作者：
Jurt, U;Gori, T;Parker, JD
目的比较硝酸甘油(GTN)和四硝酸季戊四醇(PETN)对硝酸甘油(GTN)的耐受性。背景：GTN持续治疗可引起耐受性，并与内皮细胞产生的氧自由基增加有关。季戊四醇四硝酸酯是一种用于心绞痛治疗的有机硝酸盐。目前还没有关于人类对PETN的耐受性的研究。动物实验表明，持续应用PETN不会增加自由基的产生或血流动力学耐受性。方法将30名健康志愿者随机分为GTN持续治疗(0.6 mg/h/24 h)、长效PETN(60 mg/d，3次/d)和不治疗(对照组)，疗程7天。我们用应变容积图研究了GTN的全身血压反应和静脉容量反应。结果GTN组大鼠出现耐受性，血压和前臂体积图显示耐受性，而PETN组则无此现象(p<；0.05)。GTN治疗与血浆脂质过氧化标志物显著增加有关。在使用PETN(异前列腺素：对照：38+/-5；GTN：59+/-6；PETN：38+/-3mug/ml；p<；0.005)治疗的患者中没有观察到这种反应。结论PETN治疗不会导致耐受性，也与自由基产生增加的证据无关。(C)2001年，美国心脏病学会
OBJECTIVES We investigated the development of nitrate tolerance after continuous exposure to nitroglycerin (GTN) as compared with pentaerythritol tetranitrate (PETN) in humans.BACKGROUND Sustained therapy with GTN causes tolerance and has been associated with increased production of free oxygen radicals by the endothelium. Pentaerythritol tetranitrate is an organic nitrate that has been used in the therapy of angina. There have been no investigations concerning the development of tolerance to PETN in humans. Animal investigations suggested that continuous therapy with PETN does not cause increased free radical production or hemodynamic tolerance.METHODS We randomized 30 healthy volunteers to continuous GTN (0.6 mg/h/24 h), long-acting PETN (60 mg orally three times a day) or no treatment (control group) for seven days. We studied systemic blood pressure responses and venous volume responses to GTN with strain-gauge plethysmography. The levels of cytotoxic aldehydes and isoprostanes were measured as markers of free radical-mediated lipid peroxidation.RESULTS Tolerance, as demonstrated by blood pressure and forearm plethysmography, developed in the GTN group and was absent in the PETN group (p < 0.05). Therapy with GTN was associated with a significant increase in plasma markers of lipid peroxidation. This response was not observed in those treated with PETN (isoprostanes: control: 38 +/- 5; GTN: 59 +/- 6; PETN: 38 +/- 3 mug/ml; p < 0.005).CONCLUSIONS Treatment with PETN does not cause tolerance and is not associated with evidence of increased free radical production. (C) 2001 by the American College of Cardiology