Kawamoto J H, Brien J F, Marks G S, Nakatsu K
Can J Physiol Pharmacol. 1987 Jun;65(6):1146-50. doi: 10.1139/y87-181.
Recent evidence supports the hypothesis that the mechanism by which glyceryl trinitrate induces relaxation of vascular smooth muscle involves the biotransformation of glyceryl trinitrate. This study was conducted to determine if there was a direct correlation between the capacity of vascular smooth muscle preparations to biotransform glyceryl trinitrate and their sensitivity to the relaxant effect of this organic nitrate. Isolated bovine pulmonary arteries and veins were contracted submaximally and cumulative dose-response relationships to glyceryl trinitrate were obtained; the vein was approximately 10 times more sensitive than the artery to glyceryl trinitrate induced relaxation. In a separate series of experiments, these vascular tissues were contracted submaximally and incubated with 0.5 microM [14C]glyceryl trinitrate for 2 min, during which glyceryl trinitrate induced relaxation was monitored. At 2 min, tissue samples were taken for determination of glyceryl trinitrate and glyceryl-1,2- and 1,3-dinitrate content by thin-layer chromatography and liquid scintillation spectrometry. Biotransformation of glyceryl trinitrate to glyceryl dinitrate occurred concomitantly with relaxation of these blood vessels. The concentration of glyceryl dinitrate in the vein was significantly less than that in the artery (p less than or equal to 0.05), even though significantly greater relaxation of the vein than the artery was observed (p less than or equal to 0.05). From these data, a simple linear relationship between glyceryl trinitrate biotransformation and relaxation is not apparent.
近期证据支持这样一种假说，即硝酸甘油诱导血管平滑肌舒张的机制涉及硝酸甘油的生物转化。本研究旨在确定血管平滑肌制剂生物转化硝酸甘油的能力与其对这种有机硝酸盐舒张作用的敏感性之间是否存在直接关联。将离体牛肺动脉和静脉进行亚最大收缩，然后获得对硝酸甘油的累积剂量 - 反应关系；静脉对硝酸甘油诱导的舒张作用的敏感性约为动脉的10倍。在另一系列实验中，将这些血管组织进行亚最大收缩，并与0.5微摩尔[14C]硝酸甘油孵育2分钟，在此期间监测硝酸甘油诱导的舒张情况。2分钟时，采集组织样本，通过薄层色谱法和液体闪烁光谱法测定硝酸甘油以及甘油 - 1,2 - 二硝酸酯和1,3 - 二硝酸酯的含量。硝酸甘油向甘油二硝酸酯的生物转化与这些血管的舒张同时发生。静脉中甘油二硝酸酯的浓度显著低于动脉中的浓度（p≤0.05），尽管观察到静脉的舒张程度明显大于动脉（p≤0.05）。从这些数据来看，硝酸甘油生物转化与舒张之间不存在明显的简单线性关系。
