{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:51:23Z","timestamp":1789732283215,"version":"4.0.1"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2001,5,8]]},"abstract":"<jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    \u2014Chronic hypoxia has been shown to modulate nitric oxide (NO) responses in different cell models, but the relationship between hypoxia and NO synthase (NOS) regulation in humans was not studied. We studied the relationship between endothelial and inducible NOS (eNOS and iNOS) activities and expression and chronic hypoxia in children with cyanotic and acyanotic congenital heart defects.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Methods and Results<\/jats:italic>\n                    \u2014Right atrial tissue was excised from 18 patients during cardiac surgery. eNOS and iNOS activities were measured by conversion of\n                    <jats:sc>l<\/jats:sc>\n                    -[H\n                    <jats:sup>3<\/jats:sup>\n                    ]arginine to\n                    <jats:sc>l<\/jats:sc>\n                    -[H\n                    <jats:sup>3<\/jats:sup>\n                    ]citrulline. Gene expression of eNOS and iNOS was quantified by competitive reverse transcription\u2013polymerase chain reaction. The eNOS activity and expression were significantly reduced in cyanotic hearts compared with acyanotic hearts: 0.38\u00b10.14 versus 1.06\u00b10.11 pmol \u00b7 mg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7 min\n                    <jats:sup>\u22121<\/jats:sup>\n                    (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.0001) and 0.54\u00b10.08 versus 0.80\u00b10.10 relative optical density (ROD) of cDNA (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.0001), respectively. In contrast, iNOS activity and expression were significantly higher in cyanotic than in acyanotic children: 7.04\u00b11.20 versus 4.17\u00b11.10 pmol \u00b7 mg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7 min\n                    <jats:sup>\u22121<\/jats:sup>\n                    (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.0001) and 2.55\u00b10.11 versus 1.91\u00b10.18 ROD of cDNA (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.0001), respectively.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusions<\/jats:italic>\n                    \u2014Hypoxia downregulates eNOS activity and gene expression in cardiac tissue from patients with cyanotic congenital heart defects. By contrast, iNOS activity and expression are increased in cyanotic children and may represent an alternative mechanism to counteract the effects of hypoxia in the cardiovascular system. Therefore, a novel adaptive mechanism during hypoxia is suggested.\n                  <\/jats:p>","DOI":"10.1161\/01.cir.103.18.2272","type":"journal-article","created":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T20:09:32Z","timestamp":1339445372000},"page":"2272-2276","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":77,"title":["Influence of Hypoxia on Nitric Oxide Synthase Activity and Gene Expression in Children With Congenital Heart Disease"],"prefix":"10.1161","volume":"103","author":[{"given":"Carlos Regenga","family":"Ferreiro","sequence":"first","affiliation":[{"name":"From the Atherosclerosis Unit, Heart Institute (INCOR) (A.C.P.C., P.L.L.), and the Department of Pharmacology, Institute of Biomedical Sciences (A.P.D., M.H.C.C.), University of Sa\u0303o Paulo; and the Heart Hospital of the Syrian Sanatorium Association (C.R.F., M.B.J., L.C.B.S.), Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Carlos Palandri","family":"Chagas","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Unit, Heart Institute (INCOR) (A.C.P.C., P.L.L.), and the Department of Pharmacology, Institute of Biomedical Sciences (A.P.D., M.H.C.C.), University of Sa\u0303o Paulo; and the Heart Hospital of the Syrian Sanatorium Association (C.R.F., M.B.J., L.C.B.S.), Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Helena Catelli","family":"Carvalho","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Unit, Heart Institute (INCOR) (A.C.P.C., P.L.L.), and the Department of Pharmacology, Institute of Biomedical Sciences (A.P.D., M.H.C.C.), University of Sa\u0303o Paulo; and the Heart Hospital of the Syrian Sanatorium Association (C.R.F., M.B.J., L.C.B.S.), Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Dantas","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Unit, Heart Institute (INCOR) (A.C.P.C., P.L.L.), and the Department of Pharmacology, Institute of Biomedical Sciences (A.P.D., M.H.C.C.), University of Sa\u0303o Paulo; and the Heart Hospital of the Syrian Sanatorium Association (C.R.F., M.B.J., L.C.B.S.), Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Biscegli","family":"Jatene","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Unit, Heart Institute (INCOR) (A.C.P.C., P.L.L.), and the Department of Pharmacology, Institute of Biomedical Sciences (A.P.D., M.H.C.C.), University of Sa\u0303o Paulo; and the Heart Hospital of the Syrian Sanatorium Association (C.R.F., M.B.J., L.C.B.S.), Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Carlos","family":"Bento de Souza","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Unit, Heart Institute (INCOR) (A.C.P.C., P.L.L.), and the Department of Pharmacology, Institute of Biomedical Sciences (A.P.D., M.H.C.C.), University of Sa\u0303o Paulo; and the Heart Hospital of the Syrian Sanatorium Association (C.R.F., M.B.J., L.C.B.S.), Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prota\u0301sio","family":"Lemos da Luz","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Unit, Heart Institute (INCOR) (A.C.P.C., P.L.L.), and the Department of Pharmacology, Institute of Biomedical Sciences (A.P.D., M.H.C.C.), University of Sa\u0303o Paulo; and the Heart Hospital of the Syrian Sanatorium Association (C.R.F., M.B.J., L.C.B.S.), Sa\u0303o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199312303292706"},{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","unstructured":"Forstemann U Closs EI Pollock JS et al. 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