{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:59:49Z","timestamp":1791417589546,"version":"4.3.3"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nitric oxide (NO) signaling plays a major role in modulating vascular tone and remodeling in the pulmonary circulation, but its role in the pathogenesis of pulmonary vascular diseases is still not completely understood. Numerous abnormalities of NO synthesis and signaling have been identified in animal models of pulmonary vascular disease and in humans with pulmonary hypertension. Many of these abnormalities have become targets of new therapies for the treatment of pulmonary hypertension. However, it is unclear to what extent alterations in NO signaling contribute to pulmonary hypertensive responses or merely reflect abnormalities induced by the underlying disease. This perspective examines the current understanding of altered NO signaling in pulmonary hypertensive diseases and discusses how these alterations may contribute to the pathogenesis of pulmonary hypertension. The efficacy and limitations of presently available therapies for pulmonary hypertension that target NO signaling are reviewed along with an update on investigational therapies that use this pathway to reverse pulmonary hypertensive changes.<\/jats:p>","DOI":"10.1164\/rccm.201304-0686pp","type":"journal-article","created":{"date-parts":[[2013,7,3]],"date-time":"2013-07-03T14:28:04Z","timestamp":1372861684000},"page":"639-646","source":"Crossref","is-referenced-by-count":206,"title":["Nitric Oxide Deficiency and Endothelial Dysfunction in Pulmonary Arterial Hypertension"],"prefix":"10.1093","volume":"188","author":[{"given":"James R.","family":"Klinger","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Sleep, and Critical Care Medicine, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven H.","family":"Abman","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine and Children\u2019s Hospital Colorado, Aurora, Colorado; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Gladwin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Vascular Medicine Institute, University of Pittsburgh Medical Center, Montefiore Hospital, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,9,15]]},"reference":[{"key":"2026032100455657400_bib1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1042\/bj3570593","article-title":"Nitric oxide synthases: structure, function and inhibition","volume":"357","author":"Alderton","year":"2001","journal-title":"Biochem J"},{"key":"2026032100455657400_bib2","first-page":"H1921","article-title":"Hypoxia inhibits expression of eNOS via 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