Vidal M, Joly G, Mombouli J V, Boulanger C M, Vanhoutte P M
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas.
J Cardiovasc Pharmacol. 1994;23 Suppl 4:S1-5.
Experiments were designed to study the effects of trandolaprilat on endothelium-dependent responses in isolated blood vessels. Rings of either femoral or left circumflex coronary arteries of the dog or thoracic aortas of normotensive rats were suspended in organ chambers for isometric tension recording. During contractions induced by prostaglandin F2 alpha, trandolaprilat did not cause direct endothelium-dependent or -independent relaxation. However, when given to preparations incubated with angiotensin I or bradykinin, the compound evoked significant endothelium-dependent relaxation. By contrast, trandolaprilat failed to cause any change in tension when given in the presence of acetylcholine (ACh). In rings of femoral arteries, trandolaprilat potentiated the endothelium-dependent relaxation evoked by bradykinin and adenosine diphosphate; it did not modify the endothelium-dependent relaxations induced by ACh, substance P, or thrombin. In rings of femoral arteries without endothelium, trandolaprilat augmented relaxation induced by adenosine diphosphate (ADP) but not by adenosine. In perfused coronary arteries with but not those without endothelium, trandolaprilat caused relaxation in the absence of exogenous bradykinin (or ADP). These experiments suggest that trandolaprilat does not directly release endothelium-derived relaxing factor from the endothelial cells, does not interfere with the ability of the endothelium to release endothelium-derived relaxing factor, augments the endothelium-dependent responses to bradykinin (given exogenously or produced locally) and angiotensin I by direct interaction with converting enzyme, and potentiates the relaxation induced by ADP by augmenting its direct effect on vascular smooth muscle.
设计实验以研究群多普利拉对离体血管内皮依赖性反应的影响。将犬的股动脉或左旋冠状动脉环或正常血压大鼠的胸主动脉环悬挂于器官浴槽中以记录等长张力。在前列腺素F2α诱导的收缩过程中，群多普利拉不会引起直接的内皮依赖性或非内皮依赖性舒张。然而，当给予与血管紧张素I或缓激肽一起孵育的标本时，该化合物可引起显著的内皮依赖性舒张。相比之下，在乙酰胆碱（ACh）存在的情况下给予群多普利拉时，其未能引起张力的任何变化。在股动脉环中，群多普利拉增强了缓激肽和二磷酸腺苷引起的内皮依赖性舒张；它并未改变由ACh、P物质或凝血酶诱导的内皮依赖性舒张。在无内皮的股动脉环中，群多普利拉增强了由二磷酸腺苷（ADP）而非腺苷诱导的舒张。在有内皮而非无内皮的灌注冠状动脉中，群多普利拉在无外源性缓激肽（或ADP）的情况下引起舒张。这些实验表明，群多普利拉不会直接从内皮细胞释放内皮源性舒张因子，不会干扰内皮释放内皮源性舒张因子的能力，通过与转化酶直接相互作用增强对缓激肽（外源性给予或局部产生）和血管紧张素I的内皮依赖性反应，并通过增强其对血管平滑肌的直接作用来增强由ADP诱导的舒张。
