Auch-Schwelk W, Kuchenbuch C, Claus M, Walther B, Bossaller C, Friedel N, Graf K, Gräfe M, Fleck E
Department of Internal Medicine and Cardiology, German Heart Institute Berlin.
Eur Heart J. 1993 Nov;14 Suppl I:154-60.
Part of the vasodilator response to angiotensin converting enzyme (ACE) inhibitors depends on stimulation of bradykinin receptors, but in most studies the anticipated increase in plasma kinin concentration during ACE inhibition was not detected. We investigated the role of local ACE inhibition on endothelial control of vascular tone. Rings of bovine coronary, renal and tail arteries, as well as human coronary arteries, were mounted in organ chambers so that the isometric force could be recorded. The ACE inhibitors, captopril, fosinoprilat, enalaprilat, lisinopril, and ramiprilat alone had no affect on the vascular tone of bovine coronary arteries with endothelium. However, these ACE inhibitors did potentiate relaxations to bradykinin and the slowly degradable bradykinin derivative [Hyp3-Tyr(Me)8]-bradykinin (3 x 10(-11) M). A similar response was observed in human coronary arteries. The response was not observed in rings of any vessel without endothelium, or after incubation with nitro-L-arginine (10(-4) M), or the bradykinin2-receptor antagonists Hoe 140 (10(-8) M). The sensitivity to bradykinin was higher and the potentiating effect of ACE inhibition larger in the bovine coronary artery than in the renal and tail artery. Thus, ACE inhibition causes selective coronary vasodilation by potentiating the bradykinin-induced release of nitric oxide from the endothelium. The related mechanism underlying these effects must occur at the surface or within the arterial wall and seems to be independent of the degradation of the kinins.
血管紧张素转换酶（ACE）抑制剂的部分血管舒张反应取决于对缓激肽受体的刺激，但在大多数研究中，未检测到ACE抑制期间血浆激肽浓度预期的升高。我们研究了局部ACE抑制对血管张力内皮控制的作用。将牛冠状动脉、肾动脉和尾动脉环以及人冠状动脉环安装在器官浴槽中，以便记录等长力。单独使用ACE抑制剂卡托普利、福辛普利拉、依那普利拉、赖诺普利和雷米普利拉对有内皮的牛冠状动脉血管张力没有影响。然而，这些ACE抑制剂确实增强了对缓激肽和缓慢降解的缓激肽衍生物[Hyp3-Tyr(Me)8]-缓激肽（3×10⁻¹¹ M）的舒张作用。在人冠状动脉中也观察到了类似的反应。在任何无内皮的血管环中，或与硝基-L-精氨酸（10⁻⁴ M）或缓激肽2受体拮抗剂Hoe 140（10⁻⁸ M）孵育后，均未观察到该反应。牛冠状动脉对缓激肽的敏感性高于肾动脉和尾动脉，ACE抑制的增强作用也更大。因此，ACE抑制通过增强缓激肽诱导的内皮一氧化氮释放而导致选择性冠状动脉舒张。这些效应的相关机制一定发生在动脉壁表面或内部，并且似乎与激肽的降解无关。
