Directed vascular expression of human cysteinyl leukotriene 2 receptor modulates endothelial permeability and systemic blood pressure

Background-The proinflammatory and vascular actions of cysteinyl leukotrienes (CysLTs) are mediated by 2 receptors: cysteinyl leukotriene 1 receptor (CysLT(1)R) and cysteinyl leukotriene 2 receptor (CysLT(2)R). However, the distinct contribution of CysLT(2)R to the vascular actions of CysLTs has not been addressed. Methods and Results-We generated an endothelial cell-specific human CysLT(2)R (EC-hCysLT(2)R) transgenic (TG) mouse model using the Tie2 promoter/enhancer. Strong expression of hCysLT(2)R in TG lung and endothelial cells, detected by real-time polymerase chain reaction, markedly enhanced CysLT-stimulated intracellular calcium mobilization compared with endogenous expression in cells from nontransgenic mice. The permeability response to exogenous LTC4 and to endogenous CysLTs evoked by passive cutaneous anaphylaxis was augmented in TG mice. The rapid, systemic pressor response to intravenous LTC4 was also diminished in TG mice coincidentally with augmented production of nitric oxide. Conclusions-The development of EC-hCysLT(2)R mice has permitted detection of distinct vascular effects of CysLTs, which can be mediated via the CysLT(2)R in vivo.