{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:24:28Z","timestamp":1792661068416,"version":"4.5.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1992,8,15]]},"abstract":"<jats:p>We have recently shown that nitric oxide or authentic endothelium-derived relaxing factor generated in a biologic system reacts in the presence of specific protein thiols to form S-nitrosoprotein derivatives that have endothelium-derived relaxing factor-like properties. The single free cysteine of serum albumin, Cys-34, is particularly reactive toward nitrogen oxides (most likely nitrosonium ion) under physiologic conditions, primarily because of its anomalously low pK; given its abundance in plasma, where it accounts for approximately 0.5 mM thiol, we hypothesized that this plasma protein serves as a reservoir for nitric oxide produced by the endothelial cell. To test this hypothesis, we developed a methodology, which involves UV photolytic cleavage of the S--NO bond before reaction with ozone for chemiluminescence detection, with which to measure free nitric oxide, S-nitrosothiols, and S-nitrosoproteins in biologic systems. We found that human plasma contains approximately 7 microM S-nitrosothiols, of which 96% are S-nitrosoproteins, 82% of which is accounted for by S-nitroso-serum albumin. By contrast, plasma levels of free nitric oxide are only in the 3-nM range. In rabbits, plasma S-nitrosothiols are present at approximately 1 microM; 60 min after administration of NG-monomethyl-L-arginine at 50 mg\/ml, a selective and potent inhibitor of nitric oxide synthetases, S-nitrosothiols decreased by approximately 40% (greater than 95% of which were accounted for by S-nitrosoproteins, and approximately 80% of which was S-nitroso-serum albumin); this decrease was accompanied by a concomitant increase in mean arterial blood pressure of 22%. These data suggest that naturally produced nitric oxide circulates in plasma primarily complexed in S-nitrosothiol species, principal among which is S-nitroso-serum albumin. This abundant, relatively long-lived adduct likely serves as a reservoir with which plasma levels of highly reactive, short-lived free nitric oxide can be regulated for the maintenance of vascular tone.<\/jats:p>","DOI":"10.1073\/pnas.89.16.7674","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:05:55Z","timestamp":1149062755000},"page":"7674-7677","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":991,"title":["Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin."],"prefix":"10.1073","volume":"89","author":[{"given":"J S","family":"Stamler","sequence":"first","affiliation":[{"name":"Department of Medicine, Harvard University, Cambridge, MA 02138."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Jaraki","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard University, Cambridge, MA 02138."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Osborne","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard University, Cambridge, MA 02138."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D I","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard University, Cambridge, MA 02138."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Keaney","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard University, Cambridge, MA 02138."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Vita","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard University, Cambridge, MA 02138."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Singel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard University, Cambridge, MA 02138."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C R","family":"Valeri","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard University, Cambridge, MA 02138."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Loscalzo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard University, Cambridge, MA 02138."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1992,8,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.89.16.7674","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:04:14Z","timestamp":1649855054000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.89.16.7674"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,8,15]]},"references-count":0,"journal-issue":{"issue":"16","published-print":{"date-parts":[[1992,8,15]]}},"alternative-id":["10.1073\/pnas.89.16.7674"],"URL":"https:\/\/doi.org\/10.1073\/pnas.89.16.7674","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,8,15]]},"assertion":[{"value":"1992-08-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}