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.
journal_name
Nat Medjournal_title
Nature medicineauthors
Takayama K,Yuhki K,Ono K,Fujino T,Hara A,Yamada T,Kuriyama S,Karibe H,Okada Y,Takahata O,Taniguchi T,Iijima T,Iwasaki H,Narumiya S,Ushikubi Fdoi
10.1038/nm1231keywords:
subject
Has Abstractpub_date
2005-05-01 00:00:00pages
562-6issue
5eissn
1078-8956issn
1546-170Xpii
nm1231journal_volume
11pub_type
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