{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T22:41:03Z","timestamp":1789598463511,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T00:00:00Z","timestamp":1701475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA HL004601\u201035"],"award-info":[{"award-number":["ZIA HL004601\u201035"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Vascular production of nitric oxide (NO) regulates vascular tone. However, highly permeable NO entering the cardiomyocyte would profoundly impact metabolism and signalling without scavenging mechanisms. The purpose of this study was to establish mechanisms of cardiac NO scavenging. Quantitative optical studies of normoxic working hearts demonstrated that micromolar NO concentrations did not alter mitochondria redox state or respiration despite detecting NO oxidation of oxymyoglobin to metmyoglobin. These data are consistent with proposals that the myoglobin\/myoglobin reductase (Mb\/MbR) system is the major NO scavenging site. However, kinetic studies in intact hearts reveal a minor role (\u223c9%) for the Mb\/MbR system in NO scavenging. <jats:italic>In vitro<\/jats:italic>, oxygenated mitochondria studies confirm that micromolar concentrations of NO bind cytochrome oxidase (COX) and inhibit respiration. Mitochondria had a very high capacity for NO scavenging, importantly, independent of NO binding to COX. NO is also known to quickly react with reactive oxygen species (ROS) <jats:italic>in vitro<\/jats:italic>. Stimulation of NO scavenging with antimycin and its inhibition by substrate depletion are consistent with NO interacting with ROS generated in Complex I or III under aerobic conditions. Extrapolating these <jats:italic>in vitro<\/jats:italic> data to the intact heart supports the hypothesis that mitochondria are a major site of cardiac NO scavenging.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15829-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Cardiomyocyte scavenging of vascular nitric oxide (NO) is critical in maintaining normal cardiac function.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Myoglobin redox cycling via myoglobin reductase has been proposed as a major NO scavenging site in the heart.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Non\u2010invasive optical spectroscopy was used to monitor the effect of NO on mitochondria and myoglobin redox state in intact beating heart and isolated mitochondria.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These non\u2010invasive studies reveal myoglobin\/myoglobin reductase plays a minor role in cardiac NO scavenging.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A high capacity for NO scavenging by heart mitochondria was demonstrated, independent of cytochrome oxidase binding but dependent on oxygen and high redox potentials consistent with generation of reactive oxygen species.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp284446","type":"journal-article","created":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T20:19:33Z","timestamp":1701548373000},"page":"73-91","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cardiac nitric oxide scavenging: role of myoglobin and 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