Endothelium-dependent vascular responses induced by leukotriene B4.

Leukotriene B(4) (LTB(4)) is an inflammatory mediator derived from the 5-lipoxygenase pathway of arachidonic acid metabolism and has recently implicated in the pathogenesis of atherosclerosis. There are two membrane bound receptors for LTB(4): BLT(1) and BLT(2), which represent the high and low affinity receptors, respectively. BLT receptors are expressed on leukocytes, and LTB(4) is a potent chemoattractant for neutrophils, eosinophils, and T lymphocytes. Recent studies have in addition shown that LTB(4) is an indirectly acting vasoconstrictor of isolated vascular preparations. In the guinea pig aorta, the LTB(4)-induced contractions were inhibited by endothelium-denudation. In addition, pre-treatment with the NO synthase inhibitor, L-NOARG, significantly enhanced the contractions induced by LTB(4). The contractile response induced by LTB(4) in the guinea pig aorta was abolished by the selective BLT(1) receptor antagonist U75302 and the expression of BLT(1) receptor mRNA in the guinea pig aorta was established by RT-PCR. Taken together, these results suggest that LTB(4) activates BLT(1) receptors on the endothelium of the guinea pig aorta, associated with the release of both contractile factors and NO.