Directed Vascular Expression of Human Cysteinyl Leukotriene 2 Receptor Modulates Endothelial Permeability and Systemic Blood Pressure

Abstract

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 LTC 4 and to endogenous CysLTs evoked by passive cutaneous anaphylaxis was augmented in TG mice. The rapid, systemic pressor response to intravenous LTC 4 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.