Schrör K, Förster S, Woditsch I, Schröder H
Institut für Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, F.R.G.
J Cardiovasc Pharmacol. 1989;14 Suppl 11:S29-34. doi: 10.1097/00005344-198906152-00006.
The release of NO from SIN-1, the active metabolite of molsidomine, was measured in vitro in Langendorff-perfused rabbit hearts. NO in the coronary effluent was determined on-line using the oxyhemoglobin technique. Left ventricular and coronary perfusion pressure were also recorded continuously. Glyceryl trinitrate and iloprost were used as reference compounds. Infusion of SIN-1 or glyceryl trinitrate into the coronary inflow resulted in a significant and dose-dependent NO release. An apparently identical response was seen when SIN-1 was infused into the coronary effluent while the response to glyceryl trinitrate was greatly reduced or abolished. The glyceryl trinitrate-induced coronary vasodilation was only slightly diminished in presence of oxyhemoglobin whereas the response to SIN-1 was abolished. This is explained by complete scavenging of NO by oxyhemoglobin within the vessel lumen. In isolated porcine aortic endothelial cells, SIN-1 induced a significant and dose-dependent increase in cyclic GMP, whereas glyceryl trinitrate was ineffective. This would argue against biotransformation of glyceryl trinitrate to NO by endothelial cells. Finally, glyceryl trinitrate-tolerant heart preparations exhibited a considerably reduced or even undetectable release of NO, whereas the response to SIN-1 was unchanged.
在Langendorff灌注兔心脏中体外测定了莫西多明的活性代谢产物SIN - 1释放的一氧化氮（NO）。使用氧合血红蛋白技术在线测定冠状动脉流出液中的NO。同时连续记录左心室和冠状动脉灌注压力。硝酸甘油和伊洛前列素用作参考化合物。向冠状动脉流入液中输注SIN - 1或硝酸甘油会导致显著且剂量依赖性的NO释放。当将SIN - 1注入冠状动脉流出液时，观察到明显相同的反应，而对硝酸甘油的反应则大大降低或消失。在存在氧合血红蛋白的情况下，硝酸甘油诱导的冠状动脉血管舒张仅略有减弱，而对SIN - 1的反应则被消除。这是由于血管腔内的氧合血红蛋白完全清除了NO所致。在分离的猪主动脉内皮细胞中，SIN - 1诱导环磷酸鸟苷（cGMP）显著且剂量依赖性增加，而硝酸甘油则无效。这表明内皮细胞不会将硝酸甘油生物转化为NO。最后，对硝酸甘油耐受的心脏制剂表现出NO释放显著减少甚至无法检测到，而对SIN - 1的反应则未改变。
