Parker J D
Department of Medicine, University of Toronto, Mount Sinai Hospital, Ontario, Canada.
J Cardiovasc Pharmacol. 1996 Nov;28(5):631-8. doi: 10.1097/00005344-199611000-00004.
Therapy with nitroglycerin is associated with the development of counterregulatory responses. This investigation documents the counterregulatory responses to once daily sustained-release isosorbide-5-mononitrate, contrasting them with those observed during continuous transdermal nitroglycerin. Twenty male volunteers were studied in a single-blind, parallel comparison of sustained-release isosorbide-5-mononitrate versus continuous transdermal nitroglycerin. This was a 5-day in-hospital study. Standing systolic blood pressure, heart rate, hematocrit, plasma catecholamines, and plasma renin activity were assessed at baseline (day 1), during 3 days of nitrate therapy (days 2-4), and on day 5, when no therapy was given. The administration of both transdermal nitroglycerin and isosorbide-5-mononitrate was associated with a decrease in systolic blood pressure and an increase in heart rate. There was loss of the systolic blood pressure effects within 48 h in both groups. The effect on heart rate was maintained over time and was greater in the isosorbide-5-mononitrate group. Nitrate therapy caused no change in plasma catecholamine concentrations and only modest changes in plasma renin activity. In both groups, there was a decrease in hematocrit, indicating an increase in plasma volume, which was maintained until the end of day 5. Further investigation revealed that this decrease in hematocrit was not the result of venous sampling and that plasma volume expansion takes > 8 h to resolve after removal of transdermal nitroglycerin. Counterregulatory responses to isosorbide-5-mononitrate are similar to those observed with continuous transdermal nitroglycerin. Plasma volume expansion occurs and is sustained during repeated dosing, whereas neurohormonal activation is modest. The study also revealed new data concerning the time course of reversal of plasma volume expansion after removal of transdermal nitroglycerin.
硝酸甘油治疗与反调节反应的发生有关。本研究记录了每日一次服用缓释5-单硝酸异山梨酯后的反调节反应，并将其与持续经皮使用硝酸甘油时观察到的反应进行对比。20名男性志愿者参与了一项单盲、平行对照研究，比较缓释5-单硝酸异山梨酯与持续经皮硝酸甘油的效果。这是一项为期5天的住院研究。在基线期（第1天）、硝酸酯治疗的3天（第2 - 4天）以及第5天（未进行治疗时），对站立位收缩压、心率、血细胞比容、血浆儿茶酚胺和血浆肾素活性进行评估。经皮硝酸甘油和5-单硝酸异山梨酯的给药均与收缩压降低和心率增加有关。两组在48小时内收缩压效应均消失。对心率的影响随时间持续存在，且在5-单硝酸异山梨酯组中更大。硝酸酯治疗对血浆儿茶酚胺浓度无影响，对血浆肾素活性仅有适度改变。两组的血细胞比容均降低，表明血浆容量增加，这种情况一直持续到第5天结束。进一步研究表明，血细胞比容的降低并非静脉采血所致，且在去除经皮硝酸甘油后，血浆容量扩张需要超过8小时才能恢复。对5-单硝酸异山梨酯的反调节反应与持续经皮使用硝酸甘油时观察到的反应相似。在重复给药期间会出现并持续血浆容量扩张，而神经激素激活程度较轻。该研究还揭示了有关去除经皮硝酸甘油后血浆容量扩张逆转时间进程的新数据。
