Leukotriene B4 is an indirectly acting vasoconstrictor in guinea pig aorta via an inducible type of BLT receptor

Leukotriene B-4 (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.