Auch-Schwelk W, Bossaller C, Claus M, Graf K, Gräfe M, Fleck E
German Heart Institute Berlin, Department of Internal Medicine and Cardiology.
Cardiovasc Res. 1993 Feb;27(2):312-7. doi: 10.1093/cvr/27.2.312.
The effect of angiotensin converting enzyme (ACE) inhibitors on vascular tone of isolated coronary arteries was determined in the presence of bradykinin and other vasodilators to elucidate the mechanisms leading to augmented bradykinin effects during ACE inhibition.
Rings of isolated bovine and human coronary arteries were mounted in organ chambers for measurement of isometric force. The effects of lisinopril, enalaprilat, and captopril were investigated in the presence of submaximal concentrations of bradykinin or other vasodilators.
ACE inhibitors alone did not affect vascular tone. Threshold concentrations of bradykinin (10(-10) M), kallidin (10(-9.5) M), and the slowly degraded bradykinin agonists D-Arg(Hyp3)-bradykinin (10(-9.5) M) and [Hyp3-Tyr(Me)8]-bradykinin (10(-10.5) M) caused partial relaxation of bovine rings with endothelium. Subsequent addition of ACE inhibitors markedly potentiated the relaxations to the kinins. Bradykinin concentrations in the organ bath measured by a specific bradykinin radioimmunoassay remained stable during the addition of lisinopril. Variation of the exposure time to bradykinin (10 to 60 min) did not affect the relaxations to the ACE inhibitor. The relaxations to lisinopril were not observed after either removal of the endothelium or incubation with nitro-l-arginine or the bradykinin-2 receptor antagonist Hoe 140. Other vasodilators including acetylcholine, adenosine diphosphate, substance P, or SIN-1 did not prime the rings to respond to ACE inhibitors. Endothelium dependent relaxation to lisinopril and captopril was also observed in human coronary arteries treated with bradykinin (> or = 10(-7) M), but not in those treated with substance P (10(-8) M).
ACE inhibitors selectively potentiate endothelium dependent relaxations to submaximal concentrations of bradykinin in bovine and human coronary arteries by a local mechanism. This effect on endothelial cells might occur in addition to augmented bradykinin concentrations in the blood and reduced angiotensin II generation.
在存在缓激肽和其他血管舒张剂的情况下，测定血管紧张素转换酶（ACE）抑制剂对离体冠状动脉血管张力的影响，以阐明ACE抑制期间导致缓激肽作用增强的机制。
将离体牛和人冠状动脉环安装在器官浴槽中以测量等长力。在次最大浓度的缓激肽或其他血管舒张剂存在的情况下，研究赖诺普利、依那普利拉和卡托普利的作用。
单独使用ACE抑制剂不影响血管张力。缓激肽（10⁻¹⁰ M）、胰激肽（10⁻⁹.⁵ M）以及缓慢降解的缓激肽激动剂D-Arg（Hyp³）-缓激肽（10⁻⁹.⁵ M）和[Hyp³-Tyr（Me）⁸]-缓激肽（10⁻¹⁰.⁵ M）的阈浓度可使带内皮的牛冠状动脉环产生部分舒张。随后加入ACE抑制剂可显著增强对激肽的舒张作用。在加入赖诺普利期间，通过特异性缓激肽放射免疫测定法测得的器官浴槽中的缓激肽浓度保持稳定。缓激肽暴露时间（10至60分钟）的变化不影响对ACE抑制剂的舒张作用。去除内皮或用硝基-L-精氨酸或缓激肽-2受体拮抗剂Hoe 140孵育后，未观察到对赖诺普利的舒张作用。其他血管舒张剂，包括乙酰胆碱、二磷酸腺苷、P物质或SIN-1，均不能使血管环对ACE抑制剂产生反应。在用缓激肽（≥10⁻⁷ M）处理的人冠状动脉中也观察到对赖诺普利和卡托普利的内皮依赖性舒张作用，但在用P物质（10⁻⁸ M）处理的冠状动脉中未观察到。
ACE抑制剂通过局部机制选择性地增强牛和人冠状动脉对次最大浓度缓激肽的内皮依赖性舒张作用。除了血液中缓激肽浓度增加和血管紧张素II生成减少外，这种对内皮细胞的作用可能也会发生。
