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Leukotriene receptors on human pulmonary vascular endothelium
Author(s) -
Ortiz J.L.,
Gorenne I.,
Cortijo J.,
Seller A.,
Labat C.,
Sarria B.,
Abram T.S.,
Gardiner P.J.,
Morcillo E.,
Brink C.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb16627.x
Subject(s) - leukotriene d4 , receptor , endothelium , nitroarginine , contraction (grammar) , leukotriene , vasodilation , medicine , endocrinology , nitric oxide , zafirlukast , chemistry , nitric oxide synthase , antagonist , asthma
1 Cysteinyl‐leukotrienes cause contractions and/or relaxations of human 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 mediated via the well‐ described LT 1 receptor. 2 In human pulmonary veins (HPV) with an intact endothelium, leukotriene D 4 (LTD 4 ) induced contraction above basal tone. This response was observed at lower concentrations of LTD 4 in the presence of nitric oxide synthase inhibitor N ω ‐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 with 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 this effect was not modified by LT 1 antagonists. 4 The results suggest that contraction of endothelium‐intact HPV by LTD 4 is partially mediated via LT 1 receptors. Further, in endothelium‐intact HPV, this contraction was opposed by a relaxation induced by LTD 4 , dependent on the release of nitric oxide, which was mediated, at least in part, via a non‐LTi receptor. In addition, LTD 4 relaxation on contracted HPA was not mediated by LT 1 receptors. 5 The mechanical effects of LTD 4 on human pulmonary vasculature are complex and involve both direct and indirect mechanisms mediated via at least two types of cysteinyl‐leukotriene receptors.