Thromboxane A2 and prostaglandin F2alpha mediate inflammatory tachycardia.
Thromboxane A2 and prostaglandin F2alpha mediate inflammatory tachycardia.
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发表时间：
2005
期刊：
影响因子：
82.9
通讯作者：
K. Takayama;Koh-ichi Yuhki;K. Ono;T. Fujino;A. Hara;Takehiro Yamada;Shuhko Kuriyama;H. Karibe
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文献类型：
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作者：
K. Takayama;Koh-ichi Yuhki;K. Ono;T. Fujino;A. Hara;Takehiro Yamada;Shuhko Kuriyama;H. Karibe
全身性炎症诱导各种适应性反应，包括心动过速。虽然炎症相关性心动过速被认为是由免疫系统的炎症信号引起的交感神经放电增加引起的，但缺乏明确的证据。前列腺素类包括前列腺素（PG）D（2）、PGE（2）、PGF（2 α）、PGI（2）和血栓素（TX）A（2），它们分别通过特异性受体DP、EP（EP（1）、EP（2）、EP（3）、EP（4））、FP、IP和TP发挥作用。在这里，我们已经研究了前列腺素类在炎症性心动过速中的作用，使用缺乏这些受体的小鼠。TXA（2）类似物I-BOP和PGF（2 α）分别通过与TP和FP受体相互作用，在体外增加野生型小鼠离体心房的搏动频率。在缺乏TP或FP受体的小鼠心房中，阿托品诱导的搏动率增加被显著抑制。通过注射脂多糖（LPS）在野生型小鼠中诱导的心动过速在TP缺陷或FP缺陷小鼠中大大减弱，并且在缺乏TP和FP的小鼠中完全不存在。β受体阻滞剂普萘洛尔不能阻断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（2 α）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, definitive proof has been lacking. Prostanoids, including prostaglandin (PG) D(2), PGE(2), PGF(2alpha), PGI(2) and thromboxane (TX) A(2), exert their actions through specific receptors: DP, EP (EP(1), EP(2), EP(3), EP(4)), FP, IP and TP, respectively. 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(2alpha) 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 wild-type animals. Our results show that inflammatory tachycardia is caused by a direct action on the heart of TXA(2) and PGF(2alpha) formed under systemic inflammatory conditions.