The effect of sildenafil on human vascular function, platelet activation, and myocardial ischemia
The effect of sildenafil on human vascular function, platelet activation, and myocardial ischemia
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DOI：
10.1016/s0735-1097(02)02139-3
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发表时间：
2002-10-02
影响因子：
24
通讯作者：
Quyyumi, AA
中科院分区：
文献类型：
--
作者：
Halcox, JPJ;Nour, KRA;Quyyumi, AA
我们研究了磷酸二酯酶5抑制剂西地那非（sildenafil）对冠状动脉和外周血管功能、血小板活化和心肌缺血的影响。背景一氧化氮（NO）通过产生环鸟苷5 '-单磷酸（cyclic guanosine 5'-monophosphate）来扩张血管并抑制血小板活化，环鸟苷5 '-monophosphate由磷酸二酯酶5型代谢。在24例患者中测定了内皮依赖性和非依赖性功能以及血小板活化。另外24例冠心病（CAD）和运动时缺血的患者和12例对照受试者在运动时以随机、双盲方式接受100 mg西地那非、10 mg硝酸异山梨酯（ISDN）或安慰剂治疗。结果西地那非（100 mg）使心外膜冠状动脉血管舒张（+6.9 +/-1.3%，p < 0.0001）。乙酰胆碱和冷加压试验的冠状动脉心外膜和微血管反应得到改善，CAD和内皮功能障碍患者的反应增强更明显。维拉帕米反应无变化。西地那非抑制静息和二磷酸腺苷刺激的血小板IIb/IIIa受体活化（p < 0.05）。对照组的肱动脉对西地那非的反应是扩张。峰值血流介导的扩张相似，但充血持续时间延长后西地那非管理（p < 0.001）。与安慰剂相比，ISDN可改善运动时心肌缺血（p < 0.05），而西地那非的作用介于两者之间。结论：西地那非可扩张CAD患者的心外膜冠状动脉，改善内皮功能障碍，抑制血小板活化。与ISDN和安慰剂相比，它对心肌缺血的作用居中。(C)2002年，美国心脏病学会基金会。
OBJECTIVES We studied the effects of sildenafil, a phosphodiesterase 5 inhibitor, on coronary and peripheral vascular function, platelet activation, and myocardial ischemia.BACKGROUND Nitric oxide vasodilates and inhibits platelet activation by generating cyclic guanosine 5'-monophosphate, which is metabolized by phosphodiesterase type 5.METHODS The effect of oral sildenafil on resting coronary vascular tone, endothelium-dependent and -independent function and platelet activation was measured in 24 patients. An additional 24 patients with coronary artery disease (CAD) and ischemia during exercise, and 12 control subjects received either 100 mg of sildenafil, 10 mg of isosorbide dinitrate (ISDN) or placebo during exercise on three separate days in a randomized, double-blind manner. Flow-mediated dilation of the brachial artery was measured, and CAD patients underwent treadmill exercise testing.RESULTS Sildenafil (100 mg) vasodilated epicardial coronary arteries (+6.9 +/- 1.3%, p < 0.0001). Coronary epicardial and microvascular responses with acetylcholine and cold-pressor testing improved, with a greater enhancement in patients with CAD and endothelial dysfunction. Verapamil responses were unchanged. Both resting and adenosine diphosphate-stimulated platelet IIb/IIIa receptor activation was inhibited by sildenafil (p < 0.05). Brachial arteries dilated in response to sildenafil in controls. Peak flow-mediated dilation was similar, but the duration of hyperemia was prolonged after sildenafil administration (p < 0.001). Compared with placebo, ISDN improved myocardial ischemia during exercise (p < 0.05), whereas the effect of sildenafil was intermediate between the two.CONCLUSIONS Sildenafil dilates epicardial coronary arteries, improves endothelial dysfunction and inhibits platelet activation in patients with CAD. It has an intermediate effect on myocardial ischemia compared with ISDN and placebo. (C) 2002 by the American College of Cardiology Foundation.