Ahlner J, Axelsson K L, Bornfeldt K
Acta Pharmacol Toxicol (Copenh). 1986;59 Suppl 6:17-25. doi: 10.1111/j.1600-0773.1986.tb02542.x.
Organic nitroesters e.g. glyceryltrinitrate (NTG) are of great clinical importance in the treatment of angina pectoris. The most important of their biological effects is vasodilation of peripheral arteries, peripheral veins and coronary arteries. Other biological effects, of unknown clinical relevance, are effects on myocardial metabolism and on platelet aggregation. In recent years evidences have accumulated that the vasodilating effects of organic nitroesters are mediated via the cGMP-system, although the exact mechanism of activation of the cGMP-producing enzyme guanylate cyclase is still obscure. Further research about this may elucidate the mechanism behind the development of tolerance. Another theory concerning the mechanism behind the vasodilating properties of NTG is that arachidonic acid metabolites are involved. However no clearcut evidences have been presented to support this theory. We show in this paper results indicating that arachidonic acid metabolites are of no importance for the vasodilating effects of NTG, at least not in vitro. NTG has also been shown to decrease the intracellular Ca2+ -concentration, an effect probably mediated via cGMP but the exact underlying mechanism is not yet fully understood.
有机硝酸酯类，如硝酸甘油（NTG），在心绞痛治疗中具有重要的临床意义。其最重要的生物学效应是外周动脉、外周静脉和冠状动脉的血管舒张。其他生物学效应，其临床相关性尚不清楚，包括对心肌代谢和血小板聚集的影响。近年来，越来越多的证据表明，有机硝酸酯类的血管舒张作用是通过cGMP系统介导的，尽管激活产生cGMP的酶鸟苷酸环化酶的确切机制仍不清楚。对此进行进一步研究可能会阐明耐受性产生背后的机制。另一种关于NTG血管舒张特性背后机制的理论是，花生四烯酸代谢产物参与其中。然而，尚未有明确的证据支持这一理论。我们在本文中展示的结果表明，花生四烯酸代谢产物对NTG的血管舒张作用并不重要，至少在体外是这样。NTG还被证明可降低细胞内Ca2+浓度，这一效应可能通过cGMP介导，但确切的潜在机制尚未完全了解。
