{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T12:58:13Z","timestamp":1768827493485,"version":"3.49.0"},"reference-count":64,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["MOP-93596 and 84290"],"award-info":[{"award-number":["MOP-93596 and 84290"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Canadian Foundation of Innovation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:p>Arginase is an enzyme that limits substrate l-arginine bioavailability for the production of nitric oxide by the nitric oxide synthases and produces l-ornithine, which is a precursor for collagen formation and tissue remodeling. We studied the pulmonary vascular effects of arginase inhibition in an established model of repeated systemic bleomycin sulfate administration in neonatal rats that results in pulmonary hypertension and lung injury mimicking the characteristics typical of bronchopulmonary dysplasia. We report that arginase expression is increased in the lungs of bleomycin-exposed neonatal rats and that treatment with the arginase inhibitor amino-2-borono-6-hexanoic acid prevented the bleomycin-induced development of pulmonary hypertension and deposition of collagen. Arginase inhibition resulted in increased l-arginine and l-arginine bioavailability and increased pulmonary nitric oxide production. Arginase inhibition also normalized the expression of inducible nitric oxide synthase, and reduced bleomycin-induced nitrative stress while having no effect on bleomycin-induced inflammation. Our data suggest that arginase is a promising target for therapeutic interventions in neonates aimed at preventing lung vascular remodeling and pulmonary hypertension.<\/jats:p>","DOI":"10.1152\/ajplung.00328.2014","type":"journal-article","created":{"date-parts":[[2015,1,17]],"date-time":"2015-01-17T03:41:44Z","timestamp":1421466104000},"page":"L503-L510","source":"Crossref","is-referenced-by-count":43,"title":["Arginase inhibition prevents bleomycin-induced pulmonary hypertension, vascular remodeling, and collagen deposition in neonatal rat lungs"],"prefix":"10.1152","volume":"308","author":[{"given":"Hartmut","family":"Grasemann","sequence":"first","affiliation":[{"name":"Program in Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children Toronto, Ontario, Canada;"},{"name":"Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rupinder","family":"Dhaliwal","sequence":"additional","affiliation":[{"name":"Program in Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children Toronto, Ontario, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julijana","family":"Ivanovska","sequence":"additional","affiliation":[{"name":"Program in Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children Toronto, Ontario, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crystal","family":"Kantores","sequence":"additional","affiliation":[{"name":"Program in Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children Toronto, Ontario, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick J.","family":"McNamara","sequence":"additional","affiliation":[{"name":"Program in Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children Toronto, Ontario, Canada;"},{"name":"Division of Neonatology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada;"},{"name":"Department of Physiology, University of Toronto, Toronto, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy A.","family":"Scott","sequence":"additional","affiliation":[{"name":"Faculty of Health and Behavioural Sciences, Division of Biomedical Sciences, Department of Health Sciences, Northern Ontario School of Medicine, Lakehead University, Ontario, Canada; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaques","family":"Belik","sequence":"additional","affiliation":[{"name":"Program in Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children Toronto, Ontario, Canada;"},{"name":"Division of Neonatology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada;"},{"name":"Department of Physiology, University of Toronto, Toronto, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Jankov","sequence":"additional","affiliation":[{"name":"Program in Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children Toronto, Ontario, Canada;"},{"name":"Division of Neonatology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada;"},{"name":"Department of Physiology, University of Toronto, Toronto, Canada;"},{"name":"Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44079"},{"key":"B2","doi-asserted-by":"crossref","first-page":"21120","DOI":"10.1016\/S0021-9258(19)36901-7","volume":"268","author":"Baek KJ","year":"1993","journal-title":"J Biol Chem"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/60.1.91"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00183.2009"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00101.2012"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.22609"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20972"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.04.027"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00111"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2007.04638.x"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1096\/fj.99-0960com"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.8.1121"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2789-5"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00434.2002"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.602532"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr304"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114081"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2003.08.003"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.17795\/jjnpp-8821"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.02.029"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00167.2014"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00180.2004"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.301.2.435"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/0305-0491(95)02138-8"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00813.2009"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00480.2005"},{"key":"B27","first-page":"954","volume":"96","author":"Kelley J","year":"1980","journal-title":"J Lab Clin Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.91393.2008"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00007.2007"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.76.2.305"},{"key":"B31","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1165\/rcmb.2013-0131OC","volume":"50","author":"Lee AH","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2005.00876.x"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00139.2009"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-89-1-122"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00234.2007"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090232"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200309-1304OC"},{"key":"B38","first-page":"922","volume":"157","author":"Morris JS","year":"2009","journal-title":"Biochem Pharmacol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e328360a3f6"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0904214"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-11-87"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200504-567OC"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01180.2011"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.210138"},{"key":"B45","first-page":"53","volume":"15","author":"Pullamsetti SS","year":"2011","journal-title":"Science Trans Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.2174\/1875042701002020009"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.157727"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00360.2006"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.169.233"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00072.2012"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00328.2010"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00278"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2011.03.079"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.53.070184.003533"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00006.2011"},{"key":"B56","first-page":"L1103","volume":"297","author":"Tourneux P","year":"2009","journal-title":"Inhaled nitric oxide improves lung structure and pulmonary hypertension in a model of bleomycin-induced bronchopulmonary dysplasia in neonatal rats. Development of novel arginase inhibitors for therapy"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3942"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00290.2007"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-198902000-00005"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/26.4.401"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1042\/bj3360001"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2003.01713.x"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2317fje"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.79.1.38"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.00328.2014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T02:07:52Z","timestamp":1690855672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00328.2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,15]]},"references-count":64,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,3,15]]}},"alternative-id":["10.1152\/ajplung.00328.2014"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00328.2014","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,15]]}}}