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Am J Physiol Heart Circ Physiol 287: H419-H424, 2004. First published March 11, 2004; doi:10.1152/ajpheart.00699.2003
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Leukotriene B4 is an indirectly acting vasoconstrictor in guinea pig aorta via an inducible type of BLT receptor

Magnus Bäck,1 Hong Qiu,2 Jesper Z. Haeggström,2 and Kiyoto Sakata1

1Division of Physiology, The National Institute of Environmental Medicine, Karolinska Institutet; and 2Division of Physiological Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden

Submitted 23 July 2003 ; accepted in final form 4 March 2004

Leukotriene B4 (LTB4) is a potent leukocyte chemoattractant recently implicated in the pathogenesis of atherosclerosis. The aim of this study was to assess the effects of LTB4 on isolated aortic preparations. Rings of guinea pig aorta were challenged with LTB4 for recording mechanical responses and measurements of mediator release, and LTB4 receptor (BLT1) expression was assessed by RT-PCR. Single concentrations of LTB4 induced concentration-dependent contractions that were inhibited by treatment with antihistamines, indomethacin, or the thromboxane receptor antagonist BAYu3405 as well as by denudation of endothelium. In addition, LTB4 increased the release of histamine and thromboxane in the bath. The contractions induced by LTB4 were inhibited by either the unselective BLT receptor antagonist ONO-4057 or the selective BLT1 receptor antagonist U-75302. Pretreatment with all-trans-retinoic acid enhanced the contractions and the release of histamine induced by LTB4, without affecting either the contractions induced by histamine or the histamine release evoked by calcium ionophore A23187. Analysis by RT-PCR indicated the expression of a BLT1 receptor in the guinea pig aorta and that BLT1 receptor mRNA was upregulated after treatment with retinoic acid. These results suggest that LTB4 contracts the guinea pig aorta via an indirect mechanism involving the release of histamine and thromboxane and that this BLT1 receptor-mediated response can be upregulated by all-trans-retinoic acid.

histamine; retinoic acid; endothelium; thromboxane



Address for reprint requests and other correspondence: M. Bäck, Cardiovascular Research Unit, Center for Molecular Medicine, Karolinska Hospital, CMM L8:03, SE-171 76 Stockholm, Sweden (E-mail: Magnus.Back{at}cmm.ki.se).




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E. Sanchez-Galan, A. Gomez-Hernandez, C. Vidal, J. L. Martin-Ventura, L. M. Blanco-Colio, B. Munoz-Garcia, L. Ortega, J. Egido, and J. Tunon
Leukotriene B4 enhances the activity of nuclear factor-{kappa}B pathway through BLT1 and BLT2 receptors in atherosclerosis
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[Abstract] [Full Text] [PDF]




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