{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T13:19:02Z","timestamp":1778678342157,"version":"3.51.4"},"reference-count":48,"publisher":"BMJ","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Heart"],"accepted":{"date-parts":[[2010,6,22]]},"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:p>Tetrahydrobiopterin (BH4) functions as a cofactor in several important enzyme systems. Substantial evidence implicates BH4 as a key regulator of endothelial nitric oxide synthase (eNOS) in the setting of endothelial dysfunction and atherosclerosis. Investigators have now taken early steps in addressing the potential of BH4 as a therapeutic strategy. However, it has become more apparent that the role of BH4 in other enzymatic pathways, including other NOS isoforms and the aromatic amino acid hydroxylases, may have a bearing on important aspects of cardiovascular homeostasis. Together with eNOS, these enzymes may play key roles in diverse cardiovascular disease states such as ischaemia-reperfusion injury, cardiac hypertrophy, cardiac autonomic function and pulmonary hypertension. This review provides an overview of the role of BH4 in cardiovascular pathophysiology.<\/jats:p>","DOI":"10.1136\/hrt.2009.180430","type":"journal-article","created":{"date-parts":[[2010,9,14]],"date-time":"2010-09-14T00:34:23Z","timestamp":1284424463000},"page":"1872-1877","source":"Crossref","is-referenced-by-count":46,"title":["Tetrahydrobiopterin: pleiotropic roles in cardiovascular pathophysiology"],"prefix":"10.1136","volume":"96","clinical-trial-number":[{"clinical-trial-number":"nct00423280","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00423280","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Colin","family":"Cunnington","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith M","family":"Channon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2010,9,13]]},"reference":[{"key":"2025092004053499000_96.23.1872.1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000110785.96039.f6"},{"key":"2025092004053499000_96.23.1872.2","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3470001"},{"key":"2025092004053499000_96.23.1872.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.16.9220"},{"key":"2025092004053499000_96.23.1872.4","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3620733"},{"key":"2025092004053499000_96.23.1872.5","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.744540"},{"key":"2025092004053499000_96.23.1872.6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.704155"},{"key":"2025092004053499000_96.23.1872.7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117221"},{"key":"2025092004053499000_96.23.1872.8","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000012748.58444.08"},{"key":"2025092004053499000_96.23.1872.9","doi-asserted-by":"publisher","DOI":"10.1038\/nm1490"},{"key":"2025092004053499000_96.23.1872.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.12.062"},{"key":"2025092004053499000_96.23.1872.11","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051551"},{"key":"2025092004053499000_96.23.1872.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(01)02317-2"},{"key":"2025092004053499000_96.23.1872.13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119131"},{"key":"2025092004053499000_96.23.1872.14","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.86.2.e36"},{"key":"2025092004053499000_96.23.1872.15","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200002000-00001"},{"key":"2025092004053499000_96.23.1872.16","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.142257"},{"key":"2025092004053499000_96.23.1872.17","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jhh.1002329"},{"key":"2025092004053499000_96.23.1872.18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702986104"},{"key":"2025092004053499000_96.23.1872.19","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.6.1423"},{"key":"2025092004053499000_96.23.1872.20","doi-asserted-by":"publisher","DOI":"10.1067\/mtc.2002.124393"},{"key":"2025092004053499000_96.23.1872.21","doi-asserted-by":"crossref","first-page":"H2360","DOI":"10.1152\/ajpheart.2000.279.5.H2360","article-title":"Biphasic response of cardiac NO synthase isoforms to ischemic preconditioning in conscious rabbits","volume":"279","author":"Xuan","year":"2000","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2025092004053499000_96.23.1872.22","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.566190"},{"key":"2025092004053499000_96.23.1872.23","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2009.051417"},{"key":"2025092004053499000_96.23.1872.24","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000254415.31362.a7"},{"key":"2025092004053499000_96.23.1872.25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200521968"},{"key":"2025092004053499000_96.23.1872.26","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.737031"},{"key":"2025092004053499000_96.23.1872.27","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.883777"},{"key":"2025092004053499000_96.23.1872.28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2356"},{"key":"2025092004053499000_96.23.1872.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.182225899"},{"key":"2025092004053499000_96.23.1872.30","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000162470.26840.89"},{"key":"2025092004053499000_96.23.1872.31","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000163268.32638.F4"},{"key":"2025092004053499000_96.23.1872.32","doi-asserted-by":"publisher","DOI":"10.1089\/152308603770380061"},{"key":"2025092004053499000_96.23.1872.33","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00188809"},{"key":"2025092004053499000_96.23.1872.34","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)11144-8"},{"key":"2025092004053499000_96.23.1872.35","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1042\/cs0970005","article-title":"Role of nitric oxide in the regulation of cardiovascular autonomic control","volume":"97","author":"Chowdhary","year":"1999","journal-title":"Clin Sci (Lond)"},{"key":"2025092004053499000_96.23.1872.36","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31093"},{"key":"2025092004053499000_96.23.1872.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2008.04.007"},{"key":"2025092004053499000_96.23.1872.38","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa072366"},{"key":"2025092004053499000_96.23.1872.39","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000105581.01815.C6"},{"key":"2025092004053499000_96.23.1872.40","doi-asserted-by":"crossref","first-page":"25722","DOI":"10.1016\/S0021-9258(18)35667-9","article-title":"Tetrahydrobiopterin synthesis: an absolute requirement for cytokine-induced nitric oxide generation by vascular smooth muscle","volume":"267","author":"Gross","year":"1992","journal-title":"J Biol Chem"},{"key":"2025092004053499000_96.23.1872.41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.39.23928"},{"key":"2025092004053499000_96.23.1872.42","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/86.4.578"},{"key":"2025092004053499000_96.23.1872.43","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.0348"},{"key":"2025092004053499000_96.23.1872.44","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(96)00511-4"},{"key":"2025092004053499000_96.23.1872.45","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(99)00523-9"},{"key":"2025092004053499000_96.23.1872.46","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2007.122184"},{"key":"2025092004053499000_96.23.1872.47","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61234-3"},{"key":"2025092004053499000_96.23.1872.48","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.612325"}],"container-title":["Heart"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/hrt.2009.180430","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T11:05:43Z","timestamp":1758366343000},"score":1,"resource":{"primary":{"URL":"https:\/\/heart.bmj.com\/lookup\/doi\/10.1136\/hrt.2009.180430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,13]]},"references-count":48,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2010,11,9]]},"published-print":{"date-parts":[[2010,12]]}},"alternative-id":["10.1136\/hrt.2009.180430"],"URL":"https:\/\/doi.org\/10.1136\/hrt.2009.180430","relation":{},"ISSN":["1355-6037","1468-201X"],"issn-type":[{"value":"1355-6037","type":"print"},{"value":"1468-201X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,13]]}}}