尼可地尔、匹那地尔、尼卡地平和硝酸甘油对清醒犬冠状动脉血管作用的比较：内皮的作用

Comparisons of the effects of nicorandil, pinacidil, nicardipine and nitroglycerin on coronary vessels in the conscious dog: role of the endothelium.

Ghaleh B, Dubois-Randé J L, Hittinger L, Giudicelli J F, Berdeaux A

Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, France.

Br J Pharmacol. 1995 Jan;114(2):496-502. doi: 10.1111/j.1476-5381.1995.tb13254.x.

Abstract

The vasodilator properties of nicorandil on large and small coronary arteries were compared to those of nicardipine, pinacidil, nitroglycerin and acetylcholine in six conscious dogs. 2. Intravenous bolus injections of acetylcholine (0.1 micrograms kg-1), nitroglycerin (0.3-3 micrograms kg-1), pinacidil (10-100 micrograms kg-1), nicardipine (3-30 micrograms kg-1) and nicorandil (10-100 micrograms kg-1) dose-dependently increased circumflex coronary artery diameter and decreased coronary vascular resistance, indicating vasodilator effects on both conduit and resistance coronary arteries. 3. Three days after removal of the endothelium of the circumflex coronary artery (balloon angioplasty), pinacidil- and nicardipine-induced dilation of large coronary arteries was greatly reduced (both -76%, P < 0.01) whereas that produced by nitroglycerin and nicorandil was decreased only slightly and to a similar extent for both drugs (-19%, P < 0.01 and -28%, P < 0.05, respectively). 4. Thus in conscious dogs, nicardipine- and pinacidil-induced dilatation of large coronary arteries is endothelium-dependent. In contrast, the vasodilator effects of nitroglycerin and nicorandil on conduit vessels are endothelium-independent. 5. Finally, our results demonstrate that nicorandil dilates the large coronary arteries through its nitrate-like action and that the ATP-potassium channel opening properties of the drug are not involved in this effect in the conscious dog.

摘要

在6只清醒犬中，比较了尼可地尔对大、小冠状动脉的血管舒张特性与尼卡地平、匹那地尔、硝酸甘油和乙酰胆碱的血管舒张特性。2. 静脉推注乙酰胆碱（0.1微克/千克）、硝酸甘油（0.3 - 3微克/千克）、匹那地尔（10 - 100微克/千克）、尼卡地平（3 - 30微克/千克）和尼可地尔（10 - 100微克/千克），剂量依赖性地增加了左旋冠状动脉直径并降低了冠状动脉血管阻力，表明对冠状动脉的传导血管和阻力血管均有血管舒张作用。3. 在左旋冠状动脉内皮去除（球囊血管成形术）3天后，匹那地尔和尼卡地平诱导的大冠状动脉扩张显著降低（均为-76%，P < 0.01），而硝酸甘油和尼可地尔诱导的扩张仅略有降低，且两种药物降低程度相似（分别为-19%，P < 0.01和-28%，P < 0.05）。4. 因此，在清醒犬中，尼卡地平和匹那地尔诱导的大冠状动脉扩张是内皮依赖性的。相比之下，硝酸甘油和尼可地尔对传导血管的血管舒张作用是内皮非依赖性的。5. 最后，我们的结果表明，尼可地尔通过其类硝酸盐作用扩张大冠状动脉，且该药物的ATP钾通道开放特性在清醒犬中不参与此效应。