{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T23:01:35Z","timestamp":1782601295385,"version":"3.54.5"},"reference-count":19,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:p> Hepatopulmonary syndrome (HPS) following rat common bile duct ligation results from pulmonary molecular changes that may be influenced by circulating TNF-\u03b1 and increased vascular shear stress, through activation of NF-\u03baB or Akt. Increased pulmonary microvascular endothelin B (ET<jats:sub>B<\/jats:sub>) receptor and endothelial nitric oxide synthase (eNOS) levels contribute to nitric oxide production and the development of experimental HPS. Pentoxifylline (PTX), a phosphodiesterase and nonspecific TNF-\u03b1 inhibitor, ameliorates experimental HPS when begun before hepatic injury. However, how PTX influences the molecular events associated with initiation of experimental HPS after liver injury is established is unknown. We assessed the effects of PTX on the molecular and physiological features of HPS in vivo and on shear stress or TNF-\u03b1-mediated events in rat pulmonary microvascular endothelial cells in vitro. PTX significantly improved HPS without altering portal or systemic hemodynamics and downregulated pulmonary ET<jats:sub>B<\/jats:sub> receptor levels and eNOS expression and activation. These changes were associated with a reduction in circulating TNF levels and NF-\u03baB activation and complete inhibition of Akt activation. In rat pulmonary microvascular endothelial cells, PTX inhibited shear stress-induced ET<jats:sub>B<\/jats:sub> receptor and eNOS expression and eNOS activation. These effects were also associated with inhibition of Akt activation and were reproduced by wortmanin. In contrast, TNF-\u03b1 had no effects on endothelial ET<jats:sub>B<\/jats:sub> and eNOS alterations in vitro. PTX has direct effects in the pulmonary microvasculature, likely mediated through Akt inhibition, that ameliorate experimental HPS. <\/jats:p>","DOI":"10.1152\/japplphysiol.01048.2006","type":"journal-article","created":{"date-parts":[[2006,11,16]],"date-time":"2006-11-16T20:45:49Z","timestamp":1163709949000},"page":"949-955","source":"Crossref","is-referenced-by-count":56,"title":["Pentoxifylline attenuation of experimental hepatopulmonary syndrome"],"prefix":"10.1152","volume":"102","author":[{"given":"Junlan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqun","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balu K.","family":"Chacko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh P.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Fallon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108789200"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/145.4_Pt_1.798"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1038\/21224"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1997.272.4.G779"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2004.0944.x"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.280.5.C1057"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1124\/mol.64.4.811"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20244"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(98)80152-9"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(03)00012-6"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00761.x"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200201-027OC"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00010904"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706241"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)01207-1"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00080404"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7458"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastro.2003.07.005"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1999.277.5.G944"}],"container-title":["Journal of Applied Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/japplphysiol.01048.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T16:54:00Z","timestamp":1567961640000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/japplphysiol.01048.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,3]]}},"alternative-id":["10.1152\/japplphysiol.01048.2006"],"URL":"https:\/\/doi.org\/10.1152\/japplphysiol.01048.2006","relation":{},"ISSN":["8750-7587","1522-1601"],"issn-type":[{"value":"8750-7587","type":"print"},{"value":"1522-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3]]}}}