Thromboxane A2 and prostaglandin F2α mediate inflammatory tachycardia
Thromboxane A2 and prostaglandin F2α mediate inflammatory tachycardia
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DOI：
10.1038/nm1231
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发表时间：
2005-05-01
期刊：
影响因子：
82.9
通讯作者：
Ushikubi, F
中科院分区：
文献类型：
--
作者：
Takayama, K;Yuhki, K;Ushikubi, F
全身炎症诱发各种适应性反应，包括心动过速。尽管炎症相关的心动过速被认为是由免疫系统炎症信号引起的交感神经放电增加引起的(1)，但仍缺乏明确的证据。前列腺素，包括前列腺素 (PG) D-2、PGE(2)、PGF(2 α)、PGI(2) 和血栓素 (TX) A(2)，分别通过特定受体发挥作用：DP、EP（EP1、EP2、EP3、EP4）、FP、IP 和 TP(2)。在这里，我们使用单独缺乏这些受体的小鼠检查了前列腺素类药物在炎症性心动过速中的作用。 TXA(2)类似物I-BOP和PGF(2α)分别通过与TP和FP受体的相互作用，在体外增加野生型小鼠离体心房的搏动率。缺乏 TP 或 FP 受体的小鼠心房中细胞因子诱导的搏动率增加受到显着抑制。在野生型小鼠中注射脂多糖（LPS）诱导的心动过速在TP缺陷或FP缺陷的小鼠中大大减弱，而在TP和FP同时缺乏的小鼠中完全不存在。 β-受体阻滞剂普萘洛尔不能阻止 LPS 诱导的野生型动物心率增加。我们的研究结果表明，炎症性心动过速是由全身炎症条件下形成的 TXA(2) 和 PGF(2α) 对心脏的直接作用引起的。
Systemic inflammation induces various adaptive responses including tachycardia. Although inflammation-associated tachycardia has been thought to result from increased sympathetic discharge caused by inflammatory signals of the immune system(1), definitive proof has been lacking. Prostanoids, including prostaglandin (PG) D-2, PGE(2), PGF(2 alpha), PGI(2) and thromboxane (TX) A(2), exert their actions through specific receptors: DP, EP (EP1, EP2, EP3, EP4), FP, IP and TP, respectively(2). Here we have examined the roles of prostanoids in inflammatory tachycardia using mice that lack each of these receptors individually. The TXA(2) analog I-BOP and PGF(2 alpha) each increased the beating rate of the isolated atrium of wild-type mice in vitro through interaction with TP and FP receptors, respectively. The cytokine- induced increase in beating rate was markedly inhibited in atria from mice lacking either TP or FP receptors. The tachycardia induced in wild-type mice by injection of lipopolysaccharide (LPS) was greatly attenuated in TP-deficient or FP-deficient mice and was completely absent in mice lacking both TP and FP. The beta-blocker propranolol did not block the LPS-induced increase in heart rate in wildtype animals. Our results show that inflammatory tachycardia is caused by a direct action on the heart of TXA(2) and PGF(2 alpha) formed under systemic inflammatory conditions.