{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:13:56Z","timestamp":1792300436829,"version":"4.4.0"},"reference-count":30,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5901","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2008,10,24]]},"abstract":"<jats:p>\n                    Studies of nitric oxide over the past two decades have highlighted the fundamental importance of gaseous signaling molecules in biology and medicine. The physiological role of other gases such as carbon monoxide and hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) is now receiving increasing attention. Here we show that H\n                    <jats:sub>2<\/jats:sub>\n                    S is physiologically generated by cystathionine \u03b3-lyase (CSE) and that genetic deletion of this enzyme in mice markedly reduces H\n                    <jats:sub>2<\/jats:sub>\n                    S levels in the serum, heart, aorta, and other tissues. Mutant mice lacking CSE display pronounced hypertension and diminished endothelium-dependent vasorelaxation. CSE is physiologically activated by calcium-calmodulin, which is a mechanism for H\n                    <jats:sub>2<\/jats:sub>\n                    S formation in response to vascular activation. These findings provide direct evidence that H\n                    <jats:sub>2<\/jats:sub>\n                    S is a physiologic vasodilator and regulator of blood pressure.\n                  <\/jats:p>","DOI":"10.1126\/science.1162667","type":"journal-article","created":{"date-parts":[[2008,10,23]],"date-time":"2008-10-23T17:30:17Z","timestamp":1224783017000},"page":"587-590","source":"Crossref","is-referenced-by-count":2178,"title":["H\n                    <sub>2<\/sub>\n                    S as a Physiologic Vasorelaxant: Hypertension in Mice with Deletion of Cystathionine \u03b3-Lyase"],"prefix":"10.1126","volume":"322","author":[{"given":"Guangdong","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiansong","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghe","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif K.","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weitong","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon H.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada."},{"name":"Departments of Neuroscience, Pharmacology and Molecular Sciences and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.26.041002.131047"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200406000-00002"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0211hyp"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.21.6008"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1385\/MN:26:1:013"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706014"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.07.060"},{"key":"e_1_3_1_9_2","unstructured":"Materials and methods are available as supporting material on Science 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H. Zlotkin, G. H. Anderson, Pediatr. Res.16, 65 (1982).","journal-title":"Pediatr. Res."},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1361011"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040243"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00013.2002"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00331.2004"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200310000-00015"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408997200"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-003-0906-8"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0496-386"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2006.11.012"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020150124721"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2003.08.011"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400222200"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.41.25907"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/377239a0"},{"key":"e_1_3_1_26_2","first-page":"H770","volume":"2","year":"1999","unstructured":"K. D. Lake-Bruseet al., Am. J. Physiol. Heart Circ. Physiol.2, H770 (1999).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.23.13176"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1139\/y03-077"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1080\/07853890701491000"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.17.9747"},{"key":"e_1_3_1_31_2","unstructured":"We thank C. Watkins for experimental and conceptual assistance. Supported by U.S. Public Health Service grant MH18501 and Research Scientist Award DA00074 to S.H.S. and operating grants of Canadian Institutes of Health Research to L.W. and R.W."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1162667","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T03:11:38Z","timestamp":1704856298000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1162667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,24]]},"references-count":30,"journal-issue":{"issue":"5901","published-print":{"date-parts":[[2008,10,24]]}},"alternative-id":["10.1126\/science.1162667"],"URL":"https:\/\/doi.org\/10.1126\/science.1162667","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1127807.603995","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1127807.584893","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,24]]}}}