Protective role of bradykinin in cardiac anaphylaxis. Coronary-vasodilating and antiarrhythmic activities mediated by autocrine/paracrine mechanisms.
Protective role of bradykinin in cardiac anaphylaxis. Coronary-vasodilating and antiarrhythmic activities mediated by autocrine/paracrine mechanisms.
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缓激肽在心脏过敏反应中的保护作用。
DOI：
10.1161/01.res.76.3.434
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发表时间：
1995
影响因子：
20.1
通讯作者：
Levi,R
中科院分区：
文献类型：
--
作者：
Rubin,LE;Levi,R
心脏过敏反应是一种急性缺血性功能障碍，包括冠状动脉血管收缩和心律失常，是临床公认的影响心脏的速发型超敏反应模型。缓激肽是一种超敏反应介质，也是一种有效的冠状血管扩张剂，通过一氧化氮和前列环素的产生起作用。由于缺血增加了缓激肽从心脏流出，我们怀疑缓激肽是否可以减轻过敏性冠状血管收缩。从致敏豚鼠分离的心脏的抗原激发与缓激肽溢出增加约30%相关。此外，（1）当使用激肽酶II/血管紧张素转换酶抑制剂卡托普利和依那普利拉延长缓激肽的半衰期时，过敏性冠状血管收缩减弱并逆转，心律失常减轻;（2）缓激肽B2受体拮抗剂HOE 140可预防这些作用;（3）HOE 140可加重过敏性冠状血管收缩和心律失常。在心脏过敏反应期间，cGMP（一氧化氮产生的标志物）和6-酮前列腺素F1α（一种稳定的前列环素代谢物）的冠状动脉溢出分别增加了两倍和四倍。由于依那普利拉和HOE 140均不影响这些变化，cGMP和6-酮前列腺素F1α的溢出增强可能反映了其他超敏反应介质（例如组胺和白三烯）的作用。我们推测缓激肽在心脏过敏反应中起保护作用，通过在冠状动脉内皮的管腔表面积累，并以自分泌模式促进B2受体介导的一氧化氮和前列环素的产生，其浓度足以引起对冠状动脉血管平滑肌的旁分泌作用，从而对抗其他过敏介质的血管收缩作用。
Cardiac anaphylaxis, an acute ischemic dysfunction comprising coronary vasoconstriction and arrhythmias, is a model of clinically recognized immediate hypersensitivity reactions affecting the heart. Bradykinin, a mediator of hypersensitivity, is also a potent coronary vasodilator, acting via nitric oxide and prostacyclin production. Because ischemia increases bradykinin outflow from the heart, we questioned whether bradykinin might mitigate anaphylactic coronary vasoconstriction. Antigen challenge of hearts isolated from presensitized guinea pigs was associated with an ≈30% increase in bradykinin overflow. Furthermore, (1) when the half-life of bradykinin was prolonged with the kininase II/angiotensin-converting enzyme inhibitors captopril and enalaprilat, anaphylactic coronary vasoconstriction was attenuated and reversed, and arrhythmias were alleviated; (2) the bradykinin B2-receptor antagonist HOE 140 prevented these effects; and (3) HOE 140 exacerbated both anaphylactic coronary vasoconstriction and arrhythmias. During cardiac anaphylaxis, the coronary overflow of cGMP, a marker of nitric oxide production, and 6-ketoprostaglandin F1α, a stable prostacyclin metabolite, increased twofold and fourfold, respectively. Because neither enalaprilat nor HOE 140 affected these changes, the enhanced overflow of cGMP and 6-ketoprostaglandin F1αis likely to reflect the actions of other hypersensitivity mediators (eg, histamine and leukotrienes). We postulate that bradykinin plays a protective role in cardiac anaphylaxis by accumulating at the luminal surface of the coronary endothelium and promoting, in an autocrine mode, a B2-receptor–mediated production of nitric oxide and prostacyclin in concentrations sufficient to elicit a paracrine effect on coronary vascular smooth muscle, thus opposing the vasoconstricting effects of other anaphylactic mediators.