{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:42:07Z","timestamp":1777873327351,"version":"3.51.4"},"reference-count":39,"publisher":"Frontiers Media SA","issue":"11","license":[{"start":{"date-parts":[[2007,12,1]],"date-time":"2007-12-01T00:00:00Z","timestamp":1196467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:p>\n                    A limited number of nitric oxide (NO)-generating drugs are available for clinical use for acute and chronic conditions. Most of these agents are organic nitrates, which do not directly release NO; tolerance to the drugs develops, in part, as a consequence of their conversion to NO. We synthesized nitrosyl-cobinamide (NO-Cbi) from cobinamide, a structural analog of cobalamin (vitamin B\n                    <jats:sub>12<\/jats:sub>\n                    ). NO-Cbi is a direct NO-releasing agent that we found was stable in water, but under physiologic conditions, it released NO with a half-life of 30 mins to 1 h. We show in five different biological systems that NO-Cbi is an effective NO-releasing drug. First, in cultured rat vascular smooth muscle cells, NO-Cbi induced phosphorylation of vasodilator-stimulated phosphoprotein, a downstream target of cGMP and cGMP-dependent protein kinase. Second, in isolated Drosophila melanogaster Malpighian tubules, NO-Cbi\u2013stimulated fluid secretion was similar to that stimulated by Deta-NONOate and a cGMP analog. Third, in isolated mouse hearts, NO-Cbi increased coronary flow much more potently than nitroglycerin. Fourth, in contracted mouse aortic rings, NO-Cbi induced relaxation, albeit to a lesser extent than sodium nitroprusside. Fifth, in intact mice, a single NO-Cbi injection rapidly reduced blood pressure, and blood pressure returned to normal after 45 mins; repeated NO-Cbi injections induced the expected fall in blood pressure. These studies indicate that NO-Cbi is a useful NO donor that can be used experimentally in the laboratory; moreover, it could be developed into a vasodilating drug for treating hypertension and potentially other diseases such as angina and congestive heart failure.\n                  <\/jats:p>","DOI":"10.3181\/0703-rm-70","type":"journal-article","created":{"date-parts":[[2008,5,12]],"date-time":"2008-05-12T19:11:21Z","timestamp":1210619481000},"page":"1432-1440","source":"Crossref","is-referenced-by-count":42,"title":["Nitrosyl-Cobinamide, a New and Direct Nitric Oxide\u2013Releasing Drug Effective\n                    <i>In Vivo<\/i>"],"prefix":"10.3389","volume":"232","author":[{"given":"Kate E.","family":"Broderick","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093; and VA San Diego Health Care System, La Jolla, California 92161"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093; and VA San Diego Health Care System, La Jolla, California 92161"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahesh","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093; and VA San Diego Health Care System, La Jolla, California 92161"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darrell D.","family":"Belke","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093; and VA San Diego Health Care System, La Jolla, California 92161"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Makino","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093; and VA San Diego Health Care System, La Jolla, California 92161"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriano","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093; and VA San Diego Health Care System, La Jolla, California 92161"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Virgil L.","family":"Woods","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093; and VA San Diego Health Care System, La Jolla, California 92161"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang H.","family":"Dillmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093; and VA San Diego Health Care System, La Jolla, California 92161"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijay S.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093; and VA San Diego Health Care System, La Jolla, California 92161"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renate B.","family":"Pilz","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093; and VA San Diego Health Care System, La Jolla, California 92161"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy D.","family":"Bigby","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093; and VA San Diego Health Care System, La Jolla, California 92161"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerry R.","family":"Boss","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093; and VA San Diego Health Care System, La Jolla, California 92161"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2016,11,26]]},"reference":[{"key":"bibr-R1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.47.1.365"},{"key":"bibr-R2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aco.0000192765.27453.5a"},{"key":"bibr-R3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200419267"},{"key":"bibr-R4","doi-asserted-by":"crossref","unstructured":"Daiber A, Mulsch A, Hink U, Mollnau H, Warnholtz A, Oelze M, Munzel T. 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