{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T21:44:34Z","timestamp":1790459074527,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T00:00:00Z","timestamp":1267401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Canada Foundation for Innovation"},{"DOI":"10.13039\/501100003179","name":"Alberta Heritage Foundation for Medical Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003179","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes for Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Heart and Stroke Foundation Canada"},{"name":"Stollery Children's Hospital Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital diaphragmatic hernia (CDH) is an anomaly associated with pulmonary hypoplasia and pulmonary hypertension (PH). The limited efficacy of current approaches to treat PH in CDH, including inhaled nitric oxide (NO), drives the search for other therapies. Phosphodiesterases (PDEs) degrade cyclic nucleotide second messenger cAMP and cGMP downstream of NO thereby limiting the vasodilatory response to NO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify therapeutic targets by cataloguing the expression and function of PDE isoforms in the pulmonary vasculature in nitrofen\u2010induced CDH in fetal rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods\/Results<\/jats:title><jats:p>Quantitative RT\u2010PCR revealed PDE1\u20135 and PDE9 mRNA expression in pulmonary arteries (PAs) of control and nitrofen\u2010induced CDH term fetal rats. In this order of potency, the PDE inhibitors Sildenafil (PDE5)\u2009&gt;\u2009EHNA (PDE2)\u2009&gt;\u2009Rolipram (PDE4)\u2009&gt;\u2009Cilostamide (PDE3) all dilated isolated third generation PA after pre\u2010constriction with the thromboxane analog U46619. Hyperoxic pre\u2010incubation of PAs significantly attenuated vasodilatation induced by the PDE5 inhibitor Sildenafil (65% vs. 33%,<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.004). CDH PAs dilated significantly less to PDE2 inhibitor EHNA compared to control (51% vs. 72%,<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Subsequently PDE2 protein expression was higher in PAs of CDH animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Most PDE isoforms exist in the PAs of fetal rats and their inhibition causes pulmonary vasodilatation. PDE5 inhibition was the most potent vasodilator, however, there were no differences between groups. PDE5\u2010induced vasodilatation was attenuated by hyperoxic pre\u2010incubation. PDE inhibitors might be considered therapeutic targets in combination with iNO in neonates with CDH. Pediatr Pulmonol. 2010; 45:320\u2013325. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.21181","type":"journal-article","created":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T16:52:08Z","timestamp":1267462328000},"page":"320-325","source":"Crossref","is-referenced-by-count":11,"title":["Expression and function of phosphodiesterases in nitrofen\u2010induced congenital diaphragmatic hernia in rats"],"prefix":"10.1002","volume":"45","author":[{"given":"Irene W.J.M.","family":"van der 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