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In animal models, ARDS can be induced by LPS, which can disrupt the pulmonary endothelium and epithelium and induce inflammation. We tested whether in vivo administration or ex vivo treatment with LPS alters the reactivity of intrapulmonary arteries and airways to constrictors relevant to both ARDS and PH, using the precision-cut lung slice (PCLS) technique. Mice were administered LPS (10 \u03bcg\/50 \u03bcl, intranasal) or saline daily for 4 days before collection of BAL fluid or preparation of PCLSs. Alternatively, PCLSs from naive mice were left untreated or treated ex vivo with LPS (10 \u03bcg\/ml) or TNF (10 ng\/ml) for 18 hours. Contraction to endothelin-1, U46619 (a stable mimetic of thromboxane A2), or serotonin was quantified. In vivo LPS administration increased BAL total inflammatory cells 5-fold, neutrophils 125-fold, and protein 2-fold, as well as the thickness of the pulmonary arterial smooth muscle layer. After in vivo LPS, contraction of intrapulmonary arteries in PCLSs to endothelin-1 and U46619, but not serotonin, increased, whereas bronchoconstrictor responses were unchanged. In PCLSs treated with LPS ex vivo, these differential effects on pulmonary artery and airway contraction were maintained. Although LPS increased TNF secretion from PCLSs, TNF treatment only increased U46619-induced vasoconstriction. This study demonstrates the potential contributions of LPS-induced inflammation and vascular remodeling to altered intrapulmonary artery reactivity to specific agonists, with implications for ARDS-associated PH.<\/jats:p>","DOI":"10.1165\/rcmb.2024-0249oc","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T17:21:18Z","timestamp":1734628878000},"page":"26-36","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":2,"title":["LPS Increases Artery but Not Airway Contraction in Precision-Cut Lung Slices from a Mouse Model of Acute Respiratory Distress Syndrome"],"prefix":"10.1093","volume":"73","author":[{"given":"Emma","family":"Lamanna","sequence":"first","affiliation":[{"name":"Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoe F.","family":"Kropf","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"Luong","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia"},{"name":"School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology University, Bundoora, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Narayan","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Richards","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bailey","family":"Cardwell","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon G.","family":"Royce","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia A.","family":"Nold-Petry","sequence":"additional","affiliation":[{"name":"Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; 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