{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T03:00:22Z","timestamp":1776913222004,"version":"3.51.2"},"reference-count":48,"publisher":"European Respiratory Society (ERS)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2009,10,26]]},"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:p>Platelet-activating factor (PAF) is a mediator of pulmonary oedema in acute lung injury that increases vascular permeability within minutes, partly through activation of acid sphingomyelinase (ASM). Since caveolae are rich in sphingomyelin and caveolin-1, which block endothelial nitric oxide (NO) synthase (eNOS) by direct binding, we examined the relationship between ASM, caveolin-1 and eNOS activity in the regulation of vascular permeability by PAF.<\/jats:p><jats:p>In caveolar fractions from pulmonary vascular endothelial cells (isolated from perfused rat lungs) the abundance of caveolin-1 and eNOS increased rapidly after PAF perfusion. PAF treatment decreased endothelial NO (eNO) formation as assessed by<jats:italic>in situ<\/jats:italic>fluorescence microscopy. Restoration of eNO levels with PAPA-NONOate ((Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate<jats:bold>)<\/jats:bold>mitigated the PAF-induced oedema.<\/jats:p><jats:p>PAF treatment increased the ASM activity in caveolar fractions and perfusion with ASM decreased eNO production. Pharmacological inhibition of the ASM pathway with imipramine, D609 or dexamethasone blocked the PAF-induced increase of caveolin-1 and eNOS in caveolae, and the decrease in eNO production and oedema formation.<\/jats:p><jats:p>We conclude that PAF causes ASM-dependent enrichment of caveolin-1 in caveolae of endothelial cells, leading to decreased eNO production which contributes to pulmonary oedema formation. These findings suggest rapid reduction in eNO production as a novel mechanism in the regulation of vascular permeability.<\/jats:p>","DOI":"10.1183\/09031936.00095609","type":"journal-article","created":{"date-parts":[[2009,11,20]],"date-time":"2009-11-20T02:58:05Z","timestamp":1258685885000},"page":"417-427","source":"Crossref","is-referenced-by-count":44,"title":["Platelet-activating factor reduces endothelial nitric oxide production: role of acid 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