LEUKOTRIENE RECEPTORS ON HUMAN PULMONARY VASCULAR ENDOTHELIUM

1 Cysteinyl-leukotrienes cause contractions and/or relaxations of huma n isolated pulmonary vascular preparations. Although, the localization and nature of the receptors through which these effects are mediated have not been fully characterized, some effects are indirect and not m ediated via the welldescribed LT(1) receptor. 2 In human pulmonary vei ns (HPV) with an intact endothelium, leukotriene D-4 (LTD(4)) induced contraction above basal tone. This response was observed at lower conc entrations of LTD(4) in the presence of nitric oxide synthase inhibito r N-omega-nitro-L-arginine (L-NOARG). Contractions (in the absence and presence of L-NOARG) were partially blocked by the LT(1) antagonists (MK 571 and ICI 198615). 3 LTD(4) relaxed HPV previously contracted wi th noradrenaline. This relaxation was potentiated by LT(1) antagonists , but was abolished by removal of the endothelium. LTD(4) also relaxed human pulmonary arteries (HPA) precontracted with noradrenaline but t his effect was not modified by LT(1) antagonists. 4 The results sugges t that contraction of endothelium-intact HPV by LTD(4) is partially me diated via LT(1) receptors. Further, in endothelium-intact HPV, this c ontraction was opposed by a relaxation induced by LTD(4), dependent on the release of nitric oxide, which was mediated, at least in part, vi a a non-LT(1) receptor. In addition, LTD(4), relaxation on contracted HPA was not mediated by LT(1) receptors. 5 The mechanical effects of L TD(4) on human pulmonary vasculature are complex and involve both dire ct and indirect mechanisms mediated via at least two types of cysteiny l-leukotriene receptors.