Schrör K, Woditsch I, Förster S
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, BRD.
Blood Vessels. 1991;28(1-3):62-6. doi: 10.1159/000158844.
This study investigated the release of nitric oxide (NO) from glyceryl trinitrate (GTN) and SIN-1 in Langendorff rabbit hearts. Infusion of either GTN (10-40 microM) or SIN-1 (0.45-4.5 microM) into the coronary inflow tract resulted in a decrease in coronary perfusion pressure and NO release (oxyhemoglobin technique) into the coronary effluent. NO release from SIN-1 occurred spontaneously whereas passage through the coronary circulation, i.e. active metabolism, was required for NO release from GTN. Removal of the coronary endothelium and blockade of endothelial NO formation did not affect NO release from GTN and SIN-1. In GTN-tolerant hearts, there was a considerable inhibition of GTN- but not SIN-1-induced NO formation and coronary vasodilation. These data suggest (1) that metabolic NO release from GTN occurs during passage of the coronary circulation and is independent of the presence of endothelium, and (2) reduced NO release is a major cause of nitrate tolerance.
本研究调查了硝酸甘油（GTN）和SIN-1在Langendorff兔心脏中一氧化氮（NO）的释放情况。向冠状动脉流入道输注GTN（10 - 40微摩尔）或SIN-1（0.45 - 4.5微摩尔）会导致冠状动脉灌注压降低以及冠状动脉流出液中NO释放（氧合血红蛋白技术）减少。SIN-1可自发释放NO，而GTN释放NO则需要通过冠状动脉循环，即进行活跃代谢。去除冠状动脉内皮以及阻断内皮型NO的形成并不影响GTN和SIN-1释放NO。在对GTN耐受的心脏中，GTN诱导的NO生成和冠状动脉舒张受到显著抑制，但SIN-1诱导的不受影响。这些数据表明：（1）GTN的代谢性NO释放在冠状动脉循环过程中发生，且与内皮的存在无关；（2）NO释放减少是硝酸盐耐受性的主要原因。
