La Rochelle C D, Dubois-Randé J L, Richard V, Hittinger L, Giudicelli J F, Berdeaux A
Laboratoire de Pharmacologie, Faculté de Médecine Paris-Sud, France.
J Cardiovasc Pharmacol. 1993;22 Suppl 7:S17-21.
Intravenous administration of the nitric oxide donor CAS 754 (10-100 micrograms/kg) elicited a long-lasting, highly selective, and dose-dependent increase in large epicardial coronary diameter in conscious dogs, whereas nitroglycerin (up to 0.3 micrograms/kg) induced a shorter and less selective dilation of the large conductance vessels. In contrast, acetylcholine simultaneously increased large epicardial coronary artery diameter and decreased coronary resistance, regardless of the doses administered (0.01-3 micrograms/kg). Three days after endothelium removal by limited coronary angioplasty, the vasodilator effects of acetylcholine and reactive hyperemia were suppressed, whereas those induced by CAS 754 and nitroglycerin were not significantly different from those observed before endothelium removal. These data show that the epicardial coronary vasodilator effects of both CAS 754 and nitroglycerin are endothelium-independent in vivo. Thus, the unique pharmacological profile of CAS 754 on coronary dynamics could prove to be of major importance in the treatment of angina pectoris.
静脉注射一氧化氮供体CAS 754（10 - 100微克/千克）可使清醒犬的心外膜大冠状动脉直径产生持久、高度选择性且剂量依赖性的增加，而硝酸甘油（高达0.3微克/千克）引起的大传导血管扩张持续时间较短且选择性较低。相比之下，无论给予何种剂量（0.01 - 3微克/千克），乙酰胆碱均可同时增加心外膜大冠状动脉直径并降低冠状动脉阻力。通过有限冠状动脉成形术去除内皮三天后，乙酰胆碱和反应性充血的血管舒张作用受到抑制，而CAS 754和硝酸甘油诱导的血管舒张作用与内皮去除前观察到的作用无显著差异。这些数据表明，CAS 754和硝酸甘油在心外膜冠状动脉的血管舒张作用在体内均不依赖于内皮。因此，CAS 754在冠状动脉动力学方面独特的药理学特性可能在心绞痛治疗中具有重要意义。
