POTENTIATION OF ENDOTHELIUM-DEPENDENT RELAXATIONS TO BRADYKININ BY ANGIOTENSIN-I CONVERTING ENZYME-INHIBITORS IN CANINE CORONARY-ARTERY INVOLVES BOTH ENDOTHELIUM-DERIVED RELAXING AND HYPERPOLARIZING FACTORS
POTENTIATION OF ENDOTHELIUM-DEPENDENT RELAXATIONS TO BRADYKININ BY ANGIOTENSIN-I CONVERTING ENZYME-INHIBITORS IN CANINE CORONARY-ARTERY INVOLVES BOTH ENDOTHELIUM-DERIVED RELAXING AND HYPERPOLARIZING FACTORS
复制标题
DOI：
10.1161/01.res.71.1.137
复制
发表时间：
1992-07-01
影响因子：
20.1
通讯作者：
VANHOUTTE, PM
中科院分区：
文献类型：
--
作者：
MOMBOULI, JV;ILLIANO, S;VANHOUTTE, PM
本研究旨在探讨血管紧张素转换酶（ACE）抑制剂增强缓激肽诱发的内皮依赖性舒张反应的机制。在离体犬冠状动脉中测量等长张力、组织cGMP水平和跨膜电位，作为一氧化氮和内皮源性超极化因子各自贡献的指标。血管紧张素转换酶抑制剂西拉普利拉和培哚普利拉可增强血管舒缓激肽的舒张作用。N（G）-硝基-L-精氨酸（NLA），一氧化氮合酶抑制剂，削弱舒张缓激肽。但ACE抑制剂的存在部分恢复了这种活性。缓激肽刺激cGMP的生产，这是增强显着的ACE抑制剂，表明一氧化氮的释放增强。NLA取消了缓激肽诱导的增加，无论是否存在ACE抑制剂。电生理研究表明，缓激肽引起血管平滑肌的内皮依赖性超极化，这是不敏感的NLA和增强的ACE抑制剂。缓激肽诱导的超极化和NLA抵抗性舒张是短暂的，并受到钾去极化的损害。因此，内皮源性超极化因子的产生可以解释犬冠状动脉的NLA抵抗性舒张。缓激肽引起的舒张作用不受B1激肽受体拮抗剂des-Arg 9，[Leu 8]-缓激肽的影响，但可被B2激肽受体拮抗剂D-Arg[Hyp 3，D-Phe 7]-缓激肽所拮抗。分子排阻色谱法的I-125标记的[Tyr 8]-缓激肽及其降解产物表明，分裂的激肽的隔离冠状动脉中的存在下，防止培哚普利拉。实验表明，血管紧张素转换酶抑制剂对缓激肽诱发的舒张的增强作用涉及保护缓激肽免受ACE的破坏，这导致内皮源性一氧化氮和超极化因子的产生增加，通过刺激内皮B2激肽受体。
Studies were designed to investigate the mechanisms underlying the augmentation by angiotensin I converting enzyme (ACE) inhibitors of the endothelium-dependent relaxations evoked by bradykinin. Isometric tension, tissue levels of cGMP, and transmembrane potential were measured in isolated canine coronary arteries as indications of the respective contribution of nitric oxide and endothelium-derived hyperpolarizing factor. In rings of coronary artery with endothelium, relaxations to bradykinin were potentiated by the ACE inhibitors cilazaprilat and perindoprilat. N(G)-Nitro-L-arginine (NLA), a nitric oxide synthase inhibitor, impaired relaxations to braddykinin. But the presence of ACE inhibitors partially restored this activity. Bradykinin stimulated the production of cGMP, and this was enhanced significantly by ACE inhibitors, indicating an augmented release of nitric oxide. NLA abolished the increase induced by bradykinin irrespective of the presence of ACE inhibitors. Electrophysiological studies revealed that bradykinin elicited an endothelium-dependent hyperpolarization of vascular smooth muscle that was insensitive to NLA and potentiated by ACE inhibitors. The bradykinin-induced hyperpolarization and NLA-resistant relaxations were transient and impaired by potassium depolarization. Thus, production of endothelium-derived hyperpolarizing factor may account for the NLA-resistant relaxations of canine coronary arteries. The relaxations induced by bradykinin were unaffected by the B1 kinin receptor antagonist des-Arg9,[Leu8]-bradykinin either in the absence or in the presence of NLA but were antagonized by the B2 kinin receptor antagonist D-Arg[Hyp3,D-Phe7]-bradykinin. Molecular exclusion chromatography of I-125-labeled [Tyr8]-bradykinin and its degradation products demonstrated that the breakdown of the kinin by isolated coronary arteries was prevented in the presence of perindoprilat. The experiments suggest that the potentiating effect of ACE inhibitors on relaxations evoked by bradykinin involves the protection of bradykinin from breakdown by ACE, which results in greater production of endothelium-derived nitric oxide and hyperpolarizing factor, via stimulation of endothelial B2 kinin receptors.