Meredith I T, Alison J F, Zhang F M, Horowitz J D, Harper R W
Cardiology Department, Monash Medical Centre, Clayton, Victoria, Australia.
J Am Coll Cardiol. 1993 Aug;22(2):581-7. doi: 10.1016/0735-1097(93)90068-c.
This study was designed to examine the effects of captopril on the coronary vascular responses to nitroglycerin.
The vasodilator effects of nitroglycerin are mediated by sulfhydryl-dependent bioconversion and influenced by local and systemic neural and hormonal counter-regulatory factors.
In patients with angina pectoris, the effects of 10 days of treatment with the sulfhydryl-containing angiotensin-converting enzyme inhibitor captopril on the coronary vasodilator responses to intracoronary nitroglycerin (1- to 20-micrograms doses) were examined utilizing a double-blind, placebo-controlled, randomized design. The effects of captopril on the induction of nitroglycerin tolerance were also examined after a 20-h intravenous infusion of nitroglycerin.
Captopril reduced mean arterial pressure at rest by 8 mm Hg compared with 3 mm Hg in the placebo group (p = NS) and did not affect baseline coronary blood flow (168 vs. 144 ml/min in the placebo group, standard error of the differences of means (SED) 26) or coronary vascular resistance (53 vs. 57 dynes.s.cm-5, SED 9). Intracoronary nitroglycerin increased coronary blood flow in a dose-dependent fashion in both the captopril and placebo groups (p < 0.001). However, captopril potentiated the effects of all doses of nitroglycerin and shifted the dose-response relationship to the left (p < 0.001). At the maximal dose of 20 micrograms, intracoronary nitroglycerin increased the coronary blood flow by a further 60% in the captopril group compared with placebo. After 20 h of intravenous nitroglycerin (24 +/- 3 micrograms/min), the coronary vasodilator responses to intracoronary nitroglycerin were attenuated (p < 0.02) in the placebo group. However, the responses to intracoronary nitroglycerin in the captopril group, remained similar to the responses observed before intravenous nitroglycerin exposure.
Captopril potentiates the coronary vasodilator responses of nitroglycerin in both the absence and the presence of nitroglycerin tolerance. The mechanisms and therapeutic implications of this interaction require further exploration.
本研究旨在探讨卡托普利对冠状动脉对硝酸甘油反应的影响。
硝酸甘油的血管舒张作用由巯基依赖性生物转化介导，并受局部和全身神经及激素的反调节因素影响。
在心绞痛患者中，采用双盲、安慰剂对照、随机设计，研究含巯基的血管紧张素转换酶抑制剂卡托普利治疗10天对冠状动脉对冠状动脉内硝酸甘油（1至20微克剂量）血管舒张反应的影响。在静脉输注硝酸甘油20小时后，还研究了卡托普利对硝酸甘油耐受性诱导的影响。
与安慰剂组平均动脉压静息时降低3mmHg相比，卡托普利使其降低8mmHg（p =无统计学意义），且不影响基线冠状动脉血流量（安慰剂组为168 vs. 144ml/min，均值差异标准误（SED）为26）或冠状动脉血管阻力（53 vs. 57达因·秒·厘米⁻⁵，SED为9）。冠状动脉内硝酸甘油在卡托普利组和安慰剂组中均以剂量依赖性方式增加冠状动脉血流量（p < 0.001）。然而，卡托普利增强了所有剂量硝酸甘油的作用，并使剂量反应关系向左移动（p < 0.001）。在最大剂量20微克时，冠状动脉内硝酸甘油使卡托普利组冠状动脉血流量相比安慰剂组进一步增加60%。静脉输注硝酸甘油（24 ± 3微克/分钟）20小时后，安慰剂组冠状动脉对冠状动脉内硝酸甘油的血管舒张反应减弱（p < 0.02）。然而，卡托普利组对冠状动脉内硝酸甘油的反应仍与静脉输注硝酸甘油暴露前观察到的反应相似。
无论有无硝酸甘油耐受性，卡托普利均能增强硝酸甘油的冠状动脉血管舒张反应。这种相互作用的机制和治疗意义需要进一步探索。
