Nakae I, Matsumoto T, Horie H, Yokohama H, Omura T, Minai K, Matsui T, Nozawa M, Takahashi M, Sugimoto Y, Ito M, Izumi M, Nakamura Y, Mitsunami K, Kinoshita M
First Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Japan.
J Cardiovasc Pharmacol. 2000 Jun;35(6):919-25. doi: 10.1097/00005344-200006000-00014.
We investigated the cardiovascular profile of nicorandil, an antianginal agent, in humans. Pharmacologically, nicorandil acts as both an adenosine triphosphate (ATP)-sensitive K+ (K(ATP)) channel opener and a nitrate. We examined which of these mechanistic components has a predominant vasodilatory effect at clinical doses. Fourteen patients underwent cardiac catheterization. The effects of the continuous intravenous infusion of nicorandil (12 mg/45 min) were examined in angiographically normal coronary arteries. Coronary vascular resistance was calculated from coronary artery diameter and coronary blood flow velocity measured using an intravascular Doppler catheter. We compared the hemodynamic responses to nicorandil with those to the intracoronary injection of nitroglycerin (250 microg) and papaverine (12 mg). The epicardial coronary arteries responded to nicorandil at the lowest plasma concentration examined (dilation of +14.0 +/- 3.3% at approximately 170 ng/ml), whereas dilation of the coronary resistance arteries (i.e., a decrease in coronary vascular resistance) took place only at higher concentrations (>200 ng/ml). Nitroglycerin caused no further changes in coronary artery diameter or coronary vascular resistance. Papaverine caused no further increase in coronary artery diameter, but markedly decreased coronary vascular resistance (1.6 +/- 0.3 to 0.4 +/- 0.1 mm Hg/ml/min; p < 0.05). Nicorandil significantly decreased pulmonary capillary wedge pressure (i.e., reduced cardiac preload) at a plasma level of >200 ng/ml, but did not change either systemic or pulmonary vascular resistance. Thus nicorandil preferentially dilated epicardial coronary arteries rather than coronary resistance arteries, and had a stronger effect on preload than on afterload. These changes in human coronary hemodynamics suggest that the nitrate actions of nicorandil as a coronary vasodilator predominate over those as a K(ATP) opener.
我们研究了抗心绞痛药物尼可地尔在人体中的心血管作用情况。从药理学角度来看，尼可地尔兼具三磷酸腺苷（ATP）敏感性钾离子（K(ATP)）通道开放剂和硝酸盐类药物的作用。我们探究了在临床剂量下，这些作用机制中哪一种在血管舒张效应方面起主要作用。14名患者接受了心导管检查。在冠状动脉造影显示正常的冠状动脉中，检测了持续静脉输注尼可地尔（12毫克/45分钟）的效果。冠状动脉血管阻力通过使用血管内多普勒导管测量的冠状动脉直径和冠状动脉血流速度来计算。我们将尼可地尔的血流动力学反应与冠状动脉内注射硝酸甘油（250微克）和罂粟碱（12毫克）的反应进行了比较。在心外膜冠状动脉中，在所检测的最低血浆浓度下（约170纳克/毫升时扩张了+14.0 +/- 3.3%），尼可地尔就产生了反应，而冠状动脉阻力血管的扩张（即冠状动脉血管阻力降低）仅在较高浓度（>200纳克/毫升）时才会出现。硝酸甘油未引起冠状动脉直径或冠状动脉血管阻力的进一步变化。罂粟碱未使冠状动脉直径进一步增加，但显著降低了冠状动脉血管阻力（从1.6 +/- 0.3降至0.4 +/- 0.1毫米汞柱/毫升/分钟；p < 0.05）。当血浆水平>200纳克/毫升时，尼可地尔显著降低了肺毛细血管楔压（即降低了心脏前负荷），但未改变体循环或肺循环血管阻力。因此，尼可地尔优先扩张心外膜冠状动脉而非冠状动脉阻力血管，并且对前负荷的作用强于对后负荷的作用。人体冠状动脉血流动力学的这些变化表明，尼可地尔作为冠状动脉血管舒张剂的硝酸盐类作用比其作为K(ATP)通道开放剂的作用更为显著。
