Parker J D, Parker A B, Farrell B, Parker J O
Department of Medicine, Queen's University, Kingston (Ontario) General Hospital, Canada.
Circulation. 1996 Feb 15;93(4):691-6. doi: 10.1161/01.cir.93.4.691.
Therapy with diuretics has been reported to prevent the development of nitrate tolerance. Importantly, diuretics may have independent antianginal effects through their effects on intravascular volume. The present investigation was designed to determine whether diuretic therapy could prevent the development of tolerance to continuous transdermal nitroglycerin. The study was also designed to examine whether diuretic therapy has an independent antianginal effect.
Twelve patients with chronic stable angina were studied in a randomized, double-blind, crossover trial. Patients received diuretic (hydrochlorothiazide plus amiloride) or placebo for 14 to 20 days. During each double-blind treatment period, patients underwent treadmill exercise testing on three separate occasions. The first exercise testing was performed after 7 to 10 days of single-blind, placebo transdermal nitroglycerin therapy. Subsequently, exercise testing was repeated on the first day of active transdermal nitroglycerin therapy and following 7 to 10 days of continuous transdermal nitroglycerin application. Therapy with a diuretic was associated with an increase in exercise capacity but had no effect on nitroglycerin tolerance. During therapy with placebo transdermal nitroglycerin, diuretic therapy caused an increase in treadmill walking time to the development of moderate angina compared with placebo (371 +/- 26 versus 288 +/- 16 seconds, diuretic versus placebo, P < .01). Similar results were obtained during both acute and sustained nitroglycerin therapy.
The results of this study demonstrate that therapy with a diuretic has no effect on the development of tolerance to continuous transdermal nitroglycerin. Interestingly, diuretic therapy itself has important antianginal effects and improves exercise capacity in patients with stable angina.
据报道，利尿剂治疗可预防硝酸酯类耐受性的发生。重要的是，利尿剂可能通过对血管内容量的作用而具有独立的抗心绞痛作用。本研究旨在确定利尿剂治疗是否能预防对持续经皮硝酸甘油耐受性的发生。该研究还旨在检验利尿剂治疗是否具有独立的抗心绞痛作用。
12例慢性稳定性心绞痛患者参与了一项随机、双盲、交叉试验。患者接受利尿剂（氢氯噻嗪加阿米洛利）或安慰剂治疗14至20天。在每个双盲治疗期间，患者在三个不同时间进行平板运动试验。第一次运动试验在单盲、安慰剂经皮硝酸甘油治疗7至10天后进行。随后，在活性经皮硝酸甘油治疗的第一天以及持续经皮硝酸甘油应用7至10天后重复进行运动试验。利尿剂治疗与运动能力增加相关，但对硝酸甘油耐受性无影响。在安慰剂经皮硝酸甘油治疗期间，与安慰剂相比，利尿剂治疗使出现中度心绞痛时的平板步行时间增加（利尿剂组为371±26秒，安慰剂组为288±16秒，P<0.01）。在急性和持续硝酸甘油治疗期间均获得了类似结果。
本研究结果表明，利尿剂治疗对持续经皮硝酸甘油耐受性的发生无影响。有趣的是，利尿剂治疗本身具有重要的抗心绞痛作用，并可改善稳定性心绞痛患者的运动能力。
