Nature Medicine
11, 562 - 566 (2005)
Published online: 17 April 2005; | doi:10.1038/nm1231
Thromboxane A2 and prostaglandin F2 mediate inflammatory tachycardiaKoji Takayama1, 2, Koh-ichi Yuhki1, Kyoichi Ono3, Takayuki Fujino1, Akiyoshi Hara1, Takehiro Yamada1, Shuhko Kuriyama1, Hideji Karibe1, Yuji Okada1, Osamu Takahata2, Takanobu Taniguchi4, Toshihiko Iijima3, Hiroshi Iwasaki2, Shuh Narumiya5
& Fumitaka Ushikubi11
Department of Pharmacology, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Japan. 2
Department of Anesthesiology, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Japan. 3
Department of Pharmacology, Akita University School of Medicine, Hondou 1-1-1, Akita 010-8543, Japan. 4
Department of Biochemistry, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Japan. 5
Department of Pharmacology, Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606-8315, Japan.
Correspondence should be addressed to Fumitaka Ushikubi ushikubi@asahikawa-med.ac.jpSystemic 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 system1, definitive proof has been lacking. Prostanoids, including prostaglandin (PG) D2, PGE2, PGF2 , PGI2 and thromboxane (TX) A2, exert their actions through specific receptors: DP, EP (EP1, EP2, EP3, EP4), FP, IP and TP, respectively2. Here we have examined the roles of prostanoids in inflammatory tachycardia using mice that lack each of these receptors individually. The TXA2 analog I-BOP and PGF2 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  -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 TXA2 and PGF2 formed under systemic inflammatory conditions.
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