Hütter J, Schmidt M, Rittler J
Department of Pharmacology, Schwarz GmbH, Monheim, F.R.G.
Eur J Pharmacol. 1988 Nov 1;156(2):215-22. doi: 10.1016/0014-2999(88)90324-x.
The effects of various compounds on the time course of the coronary dilating response to nitrovasodilators were studied in working rat hearts. Continuous administration of 100 microM glyceryl trinitrate (GTN) to the perfusate induced a rapid increase in coronary flow. The flow decreased to about 40% of the initial flow rise within 20 min and remained constant during the following 40 min. The flow increase induced by 100 microM SIN 1 (3-morpholino-sydnonimine), however, remained constant throughout the 60-min perfusion period. The decay of the GTN action was reduced in the presence of the thiol-containing agents L-homocysteine, L- and D-cysteine and to a lesser extent, reduced glutathione, while the initial response to GTN was only slightly enhanced. However, N-acetyl-L-cysteine caused a significant increase of the maximum response to GTN whereas the subsequent loss of GTN action was not greatly altered, suggesting that this agent exerts a potentiating action without altering tolerance. Dithiothreitol elicited a slight increase in the maximum effect of GTN, followed by a complete attenuation of the effect. These data suggest that SH group donors could exert different effects on the action of GTN while GTN tolerance is only influenced by L- and D-cysteine, L-homocysteine and reduced glutathione.
在工作的大鼠心脏中研究了各种化合物对硝基血管扩张剂冠状动脉扩张反应时间进程的影响。向灌注液中持续给予100微摩尔的三硝酸甘油酯（GTN）可使冠状动脉血流量迅速增加。血流量在20分钟内降至初始流量增加的约40%，并在随后的40分钟内保持恒定。然而，在整个60分钟的灌注期内，由100微摩尔的SIN 1（3-吗啉代-西多胺）引起的流量增加保持恒定。在含硫醇的试剂L-高半胱氨酸、L-和D-半胱氨酸以及程度较小的还原型谷胱甘肽存在下，GTN作用的衰减有所降低，而对GTN的初始反应仅略有增强。然而，N-乙酰-L-半胱氨酸使对GTN的最大反应显著增加，而随后GTN作用的丧失没有太大改变，这表明该试剂在不改变耐受性的情况下发挥增强作用。二硫苏糖醇使GTN的最大效应略有增加，随后效应完全减弱。这些数据表明，SH基团供体对GTN的作用可能产生不同影响，而GTN耐受性仅受L-和D-半胱氨酸、L-高半胱氨酸和还原型谷胱甘肽的影响。
