Hecker M, Bara A T, Busse R
Department of Applied Physiology, University of Freiburg, Germany.
Eur Heart J. 1993 Nov;14 Suppl I:161-3.
The angiotensin converting enzyme (ACE) inhibitors, moexiprilat and ramiprilat, relaxed preconstricted endothelium-intact bovine coronary artery rings and enhanced the relaxant response to bradykinin. The relaxation was observed in the presence of a cyclooxygenase inhibitor and without previous exposure to bradykinin. ACE inhibitor-dependent relaxation was attenuated by the selective B2-kinin receptor antagonist, Hoe 140, and completely abolished by removal of the endothelium. Bradykinin or moexiprilat also significantly increased the cyclic guanosine monophosphate (cGMP) content of these coronary segments, an effect which was abolished by the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (NNA), or by removal of the endothelium. NNA also diminished the relaxant response to moexiprilat, but only partially inhibited that to bradykinin, suggesting that the ACE inhibitor-induced relaxation was predominantly mediated by endothelial NO release, whereas bradykinin acted in part by another endothelium-dependent mechanism. These findings indicate that ACE inhibitors can elicit endothelium-dependent relaxations presumably by facilitating the accumulation of endothelium-derived kinins in or at the vessel wall. This local mechanism may significantly contribute to the antihypertensive action of these compounds in vivo.
血管紧张素转换酶（ACE）抑制剂莫昔普利拉和雷米普利拉可使预先收缩的、内皮完整的牛冠状动脉环舒张，并增强对缓激肽的舒张反应。在存在环氧化酶抑制剂且未预先接触缓激肽的情况下观察到了这种舒张作用。选择性B2-激肽受体拮抗剂Hoe 140可减弱ACE抑制剂依赖性舒张作用，而去除内皮则可使其完全消失。缓激肽或莫昔普利拉也可显著增加这些冠状动脉节段的环磷酸鸟苷（cGMP）含量，一氧化氮（NO）合酶抑制剂NG-硝基-L-精氨酸（NNA）或去除内皮可消除这种作用。NNA也可减弱对莫昔普利拉的舒张反应，但仅部分抑制对缓激肽的反应，这表明ACE抑制剂诱导的舒张主要由内皮释放NO介导，而缓激肽部分通过另一种内皮依赖性机制起作用。这些发现表明，ACE抑制剂可能通过促进血管壁内或血管壁处内皮衍生激肽的蓄积而引发内皮依赖性舒张。这种局部机制可能对这些化合物在体内的降压作用有显著贡献。
