{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:12:23Z","timestamp":1788628343749,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neonatal hyperoxia is a key contributor to bronchopulmonary dysplasia (BPD) which is characterized by airway hyperreactivity due to increased contraction and impaired relaxation of airway smooth muscle (ASM). This study investigated whether inhibition of the Rho\/Rho\u2010kinase signaling pathway restored tracheal smooth muscle (TSM) relaxation and reactivated the nitric oxide\u2013guanosine 3\u2032,5\u2032\u2010cyclic monophosphate (NO\u2010cGMP) pathway in neonatal rats exposed to hyperoxia. Newborn rats (P4) were exposed to either ambient air (AA;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200961) or hyperoxia (FiO\n                    <jats:sub>2<\/jats:sub>\n                    &gt;95%;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200958) for 7\u2009days. The effects of Rho\u2010kinase inhibitors (Y\u201027632 or fasudil) in\u00a0vitro (10\u2009\u03bcM) or in\u00a0vivo (10\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u2009day\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) on electric field stimulation\u2010induced TSM relaxation were assessed. In subsets of the experiment, tissues were pre\u2010incubated in a nitric oxide synthase (NOS) inhibitor\u2014\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>\u03c9<\/jats:sup>\n                    \u2010nitro\u2010L\u2010arginine methyl ester (L\u2010NAME; 100\u2009\u03bcM) or a Rho activator\u2014lysophosphatidic acid (LPA; 30\u2009\u03bcM). Rho\u2010kinase inhibitors, both in\u00a0vitro and in\u00a0vivo, restored hyperoxia\u2010impaired TSM relaxation to levels comparable to those of ambient air TSM. The relaxant responses in tissues supplemented with Y\u201027632 or fasudil were significantly increased compared to hyperoxia control (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), and the maximal values at 20\u2009V were 77.90\u2009\u00b1\u20093.80%; 81.20\u2009\u00b1\u20096.10% and 40.20\u2009\u00b1\u20093.60%, respectively. These Rho\u2010kinase inhibitor effects in TSM were attenuated by L\u2010NAME, indicating mechanistic action through the NO\u2010cGMP pathway. Activation of Rho reduced relaxation in the AA group, an effect that was reversed by Rho\u2010kinase inhibition. Hyperoxia impairs ASM in neonatal rats via upregulation of Rho\u2010kinase activity and suppression of NO\u2010cGMP signaling. Pharmacological inhibition of Rho\u2010kinase restores relaxation, highlighting its therapeutic potential for airway dysfunction in BPD.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70728","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T04:52:12Z","timestamp":1768625532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of Rho\u2010kinase restores impaired relaxation of airway smooth muscle in rat pups exposed to neonatal hyperoxia"],"prefix":"10.14814","volume":"14","author":[{"given":"Ramadan B.","family":"Sopi","sequence":"first","affiliation":[{"name":"Department of Premedical Courses, Faculty of Medicine University of Prishtina  Prishtina Kosovo"},{"name":"Department of Pediatrics, Rainbow Babies and Children's Hospital Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q\u00ebndrim","family":"Tha\u00e7i","sequence":"additional","affiliation":[{"name":"Department of Premedical Courses, Faculty of Medicine University of Prishtina  Prishtina Kosovo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Raffay","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rainbow Babies and Children's Hospital Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q\u00ebndresa","family":"Beqiraj\u2010Zeqiraj","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine University of Prishtina  Prishtina Kosovo"},{"name":"Pediatric Clinic University Clinical Centre of Kosovo  Prishtina Kosovo"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000329540"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15662"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/ppe.12444"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/phy2.105"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00145.2005"},{"key":"e_1_2_11_7_1","unstructured":"Beqiraj\u2010Zeqiraj Q.(2022).Role of Rho\/Rho\u2010kinase signaling pathways in development of bronchopulmonary dysplasia in the experimental rat model. 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