Torfgård K, Ahlner J, Axelsson K L
Department of Pharmacology, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
Pharmacol Toxicol. 1990 Sep;67(3):216-21. doi: 10.1111/j.1600-0773.1990.tb00816.x.
The effect of pertussis toxin (PTX) and the cyclic GMP lowering agent LY83583 on the relaxatory response induced by glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), isosorbide-5-mononitrate (IS-5-MN) and sodium nitroprusside (SNP) in bovine mesenteric artery (BMA) was investigated. Pretreatment with PTX (100 ng/ml; 2 hr induced a 100-fold right shift of the concentration-effect curve for GTN, while no effect on the relaxatory response elicited by ISDN, IS-5-MN or SNP was seen. The relaxatory effect of all the substances tested was markedly reduced by LY83583 (10 microM). The basal cGMP level as well as the GTN induced increase in cGMP were markedly reduced when BMA was exposed to LY83583. The substance also reduced the activation of soluble guanylate cyclase by SNP. Based on the different sensitivity towards PTX it is suggested that GTN induces vascular smooth muscle relaxation by a partly different mechanism than ISDN, IS-5-MN and SNP. As far as the GTN induced relaxation is concerned the sensitivity towards PTX indicates the involvement of regulatory component, possibly a G-protein. However, cyclic GMP seems to play a crucial role in mediating the relaxatory response of all the substances tested since the cGMP-lowering agent LY83583 markedly inhibited the relaxant response induced by all the vascular relaxant agents investigated.
研究了百日咳毒素（PTX）和环鸟苷酸降低剂LY83583对牛肠系膜动脉（BMA）中甘油三硝酸酯（GTN）、异山梨醇二硝酸酯（ISDN）、5-单硝酸异山梨酯（IS-5-MN）和硝普钠（SNP）诱导的舒张反应的影响。用PTX（100 ng/ml；2小时）预处理使GTN的浓度-效应曲线向右移动100倍，而对ISDN、IS-5-MN或SNP引起的舒张反应未见影响。LY83583（10 microM）显著降低了所有测试物质的舒张作用。当BMA暴露于LY83583时，基础cGMP水平以及GTN诱导的cGMP增加均显著降低。该物质还降低了SNP对可溶性鸟苷酸环化酶的激活作用。基于对PTX的不同敏感性，提示GTN诱导血管平滑肌舒张的机制与ISDN、IS-5-MN和SNP部分不同。就GTN诱导的舒张而言，对PTX的敏感性表明存在调节成分参与，可能是一种G蛋白。然而，环鸟苷酸似乎在介导所有测试物质的舒张反应中起关键作用，因为cGMP降低剂LY83583显著抑制了所有研究的血管舒张剂诱导的舒张反应。
