title: Thromboxane A2 and prostaglandin F2alpha mediate inflammatory tachycardia.
abstract: 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.
authors.affiliation: Department of Pharmacology, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Takayama
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Yuhki
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ono
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujino
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hara
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamada
authors.forename: Shuhko
authors.initials: S
authors.lastname: Kuriyama
authors.forename: Hideji
authors.initials: H
authors.lastname: Karibe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okada
authors.forename: Osamu
authors.initials: O
authors.lastname: Takahata
authors.forename: Takanobu
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iijima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ushikubi
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015237:Dinoprost / Q000378:metabolism / Q000494:pharmacology*; D004562:Electrocardiography; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007249:Inflammation; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011433:Propranolol / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000378:metabolism; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000378:metabolism; D013610:Tachycardia / Q000139:chemically induced / Q000378:metabolism*; D013928:Thromboxane A2 / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D011982:Receptors, Prostaglandin; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2; D011433:Propranolol; D015237:Dinoprost