Leukotriene B4is an indirectly acting vasoconstrictor in guinea pig aorta via an inducible type of BLT receptor

Abstract

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 LTB4on isolated aortic preparations. Rings of guinea pig aorta were challenged with LTB4for recording mechanical responses and measurements of mediator release, and LTB4receptor (BLT1) expression was assessed by RT-PCR. Single concentrations of LTB4induced 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, LTB4increased the release of histamine and thromboxane in the bath. The contractions induced by LTB4were inhibited by either the unselective BLT receptor antagonist ONO-4057 or the selective BLT1receptor 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 BLT1receptor in the guinea pig aorta and that BLT1receptor mRNA was upregulated after treatment with retinoic acid. These results suggest that LTB4contracts the guinea pig aorta via an indirect mechanism involving the release of histamine and thromboxane and that this BLT1receptor-mediated response can be upregulated by all -trans-retinoic acid.