Bradykinin and thromboxane A2 reciprocally interact to synergistically stimulate cardiac spinal afferents during myocardial ischemia
Bradykinin and thromboxane A2 reciprocally interact to synergistically stimulate cardiac spinal afferents during myocardial ischemia
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DOI：
10.1152/ajpheart.00782.2009
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发表时间：
2010-01-01
影响因子：
4.8
通讯作者：
Longhurst, John C.
中科院分区：
文献类型：
--
作者：
Fu, Liang-Wu;Longhurst, John C.
傅丽伟，Longhurst JC。缓激素和血栓素A(2)相互作用，协同刺激心肌缺血时的心脊髓传入。[J] .中华心脏杂志，2016,31(2):444 - 444。首次发表于2009年11月6日；doi: 10.1152 / ajpheart.00782.2009。心肌缺血是一个复杂的过程，导致多种介质的同时释放，包括血栓素a (2) （TxA(2)）和缓激素（BK），激活心脊髓传入。本研究验证了TxA(2)和BK相互作用刺激缺血敏感心脏事件的假设。从麻醉猫的左交感神经链或交感支（T-2-T-5）记录单个心脏传入单位的神经活动。共鉴定出52条缺血敏感传入神经（传导速度为0.27 ~ 3.35 m/s， A - δ纤维7条，c -纤维45条）。在给药4 min后，向左心房重复注射BK (1 μ g)， BK是一种TxA(2)模拟物（5 μ g），诱导的心脏传入反应明显大于第一次给药BK （0.61 +/- 0.14 ~ 1.95 +/- 0.29 vs. 0.66 +/- 0.09 ~ 2.75 +/- 0.34脉冲/s，第一次注射vs.第二次注射，n = 8）。相反，用bm - 13177 （30 mg/kg iv）阻断TxA(2)受体可使其他8种传入神经对BK （1 μ g到LA）的反应减弱45%。相反，重复的BK （1 μ g到LA）在6个单独的传入中诱导了一致的放电活动。然后我们观察到，U-46619 （5 μ g）和BK （1 μ g）共同给药引起的总反应明显高于单个反应的简单相加预测的反应。BK （1 μ g）对U-46619 （5 μ g）的8次心脏传入反应促进64%。相比之下，在不干预BK刺激的情况下，重复U-46619 （5 μ g）在其他7个缺血敏感事件中引起一致的反应。最后，吲哚美辛（5mg /kg iv）抑制环加氧酶消除了BK对U-46619 （5 μ g）心脏传入反应的增强作用，但没有改变对U-46619的传入反应。这些数据表明，BK和TxA(2)相互作用，刺激缺血敏感的心脏传入末端，导致协同传入反应，BK的增敏作用是由环加氧酶产物介导的。
Fu LW, Longhurst JC. Bradykinin and thromboxane A(2) reciprocally interact to synergistically stimulate cardiac spinal afferents during myocardial ischemia. Am J Physiol Heart Circ Physiol 298: H235-H244, 2010. First published November 6, 2009; doi: 10.1152/ajpheart.00782.2009.-Myocardial ischemia is a complex process leading to the simultaneous release of a number of mediators, including thromboxane A(2) (TxA(2)) and bradykinin (BK), that activate cardiac spinal afferents. The present study tested the hypothesis that TxA(2) and BK reciprocally interact to excite ischemically sensitive cardiac afferents. Nerve activity of single cardiac afferent units was recorded from the left sympathetic chain or rami communicantes (T-2-T-5) of anesthetized cats. Fifty-two ischemically sensitive afferents (conduction velocity = 0.27-3.35 m/s, 7 A delta-fibers and 45 C-fibers) were identified. Repeated injections (1 mu g) of BK into the left atrium (LA) 4 min after the administration of U-46619 (5 mu g into the LA), a TxA(2) mimetic, induced a significantly larger cardiac afferent response than the first response to BK (0.61 +/- 0.14 to 1.95 +/- 0.29 vs. 0.66 +/- 0.09 to 2.75 +/- 0.34 impulses/s, first injection vs. second injection, n = 8). Conversely, blockade of TxA(2) receptors with BM-13,177 (30 mg/kg iv) attenuated the responses of eight other afferents to BK (1 mu g into the LA) by 45%. In contrast, repeated BK (1 mu g into the LA) induced consistent discharge activity in six separate afferents. We then observed that the coadministration of U-46619 (5 mu g) and BK (1 mu g into the LA) together caused a total response that was significantly higher than the predicted response by the simple addition of the individual responses. BK (1 mu g) facilitated eight cardiac afferent responses to U-46619 (5 mu g into the LA) by 64%. In contrast, repeated U-46619 (5 mu g into the LA) without intervening BK stimulation evoked consistent responses in seven other ischemically sensitive afferents. Finally, inhibition of cyclooxygenase with indomethacin (5 mg/kg iv) eliminated the potentiating effects of BK on the cardiac afferent response to U-46619 (5 mu g into the LA) but did not alter the afferent response to U-46619. These data suggest that BK and TxA(2) reciprocally interact to stimulate ischemically sensitive cardiac afferent endings leading to synergistic afferent responses and that the BK sensitization effect is mediated by cyclooxygenase products.