{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:57:06Z","timestamp":1791320226978,"version":"4.3.1"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1999,6,25]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014The effects of transfer of the endothelial nitric oxide synthase (eNOS) gene to the lung were studied in mice. After intratracheal administration of AdCMV\u03b2gal, expression of the \u03b2-galactosidase reporter gene was detected in pulmonary airway cells, in alveolar cells, and in small pulmonary arteries. Gene expression with AdCMV\u03b2gal peaked 1 day after administration and decayed over a 7- to 14-day period, whereas gene expression after AdRSV\u03b2gal transfection peaked on day 5 and was sustained over a 21- to 28-day period. One day after administration of AdCMVeNOS, eNOS protein levels were increased, and there was a small reduction in mean pulmonary arterial pressure and pulmonary vascular resistance. The pressure-flow relationship in the pulmonary vascular bed was shifted to the right in animals transfected with eNOS, and pulmonary vasodepressor responses to bradykinin and the type V cGMP-selective phosphodiesterase inhibitor zaprinast were enhanced, whereas systemic responses were not altered. Pulmonary vasopressor responses to endothelin-1 (ET-1), angiotensin II, and ventilatory hypoxia were reduced significantly in animals transfected with the eNOS gene, whereas pressor responses to norepinephrine and U46619 were not changed. Systemic pressor responses to ET-1 and angiotensin II were similar in eNOS-transfected mice and in control mice. Intratracheal administration of AdRSVeNOS attenuated the increase in pulmonary arterial pressure in mice exposed to the fibrogenic anticancer agent bleomycin. These data suggest that transfer of the eNOS gene in vivo can selectively reduce pulmonary vascular resistance and pulmonary pressor responses to ET-1, angiotensin II, and hypoxia; enhance pulmonary depressor responses; and attenuate pulmonary hypertension induced by bleomycin. Moreover, these data suggest that in vivo gene transfer may be a useful therapeutic intervention for the treatment of pulmonary hypertensive disorders.<\/jats:p>","DOI":"10.1161\/01.res.84.12.1422","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"1422-1432","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":82,"title":["Gene Transfer of Endothelial Nitric Oxide Synthase to the Lung of the Mouse In Vivo"],"prefix":"10.1161","volume":"84","author":[{"given":"Hunter C.","family":"Champion","sequence":"first","affiliation":[{"name":"From the Departments of Pharmacology (H.C.C., T.J.B., A.L.H., P.J.K.), Anatomy (F.M.D\u2019S., J.R.J.), and Medicine (L.A.O.), Tulane University School of Medicine, New Orleans, La, and Departments of Internal Medicine and Pharmacology (K.T., D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinity J.","family":"Bivalacqua","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (H.C.C., T.J.B., A.L.H., P.J.K.), Anatomy (F.M.D\u2019S., J.R.J.), and Medicine (L.A.O.), Tulane University School of Medicine, New Orleans, La, and Departments of Internal Medicine and Pharmacology (K.T., D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona M.","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (H.C.C., T.J.B., A.L.H., P.J.K.), Anatomy (F.M.D\u2019S., J.R.J.), and Medicine (L.A.O.), Tulane University School of Medicine, New Orleans, La, and Departments of Internal Medicine and Pharmacology (K.T., D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis 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Pharmacology (H.C.C., T.J.B., A.L.H., P.J.K.), Anatomy (F.M.D\u2019S., J.R.J.), and Medicine (L.A.O.), Tulane University School of Medicine, New Orleans, La, and Departments of Internal Medicine and Pharmacology (K.T., D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald D.","family":"Heistad","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (H.C.C., T.J.B., A.L.H., P.J.K.), Anatomy (F.M.D\u2019S., J.R.J.), and Medicine (L.A.O.), Tulane University School of Medicine, New Orleans, La, and Departments of Internal Medicine and Pharmacology (K.T., D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert L.","family":"Hyman","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (H.C.C., T.J.B., A.L.H., P.J.K.), Anatomy (F.M.D\u2019S., J.R.J.), and Medicine 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