{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T12:11:49Z","timestamp":1788091909659,"version":"build-2803163510"},"reference-count":123,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"intramural NIDDK\/NIH","award":["ZIA DK 025104-15"],"award-info":[{"award-number":["ZIA DK 025104-15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>In mammals, nitric oxide (NO) is generated either by the nitric oxide synthase (NOS) enzymes from arginine or by the reduction of nitrate to nitrite by tissue xanthine oxidoreductase (XOR) and the microbiome and further reducing nitrite to NO by XOR or several heme proteins. Previously, we reported that skeletal muscle acts as a large nitrate reservoir in mammals, and this nitrate reservoir is systemically, as well as locally, used to generate nitrite and NO. Here, we report identifying two additional nitrate storage organs\u2014bone and skin. We used bolus of ingested 15N-labeled nitrate to trace its short-term fluxes and distribution among organs. At baseline conditions, the nitrate concentration in femur bone samples was 96 \u00b1 63 nmol\/g, scalp skin 56 \u00b1 22 nmol\/g, with gluteus muscle at 57 \u00b1 39 nmol\/g. In comparison, plasma and liver contained 34 \u00b1 19 nmol\/g and 15 \u00b1 5 nmol\/g of nitrate, respectively. Three hours after 15N-nitrate ingestion, its concentration significantly increased in all organs, exceeding the baseline levels in plasma, skin, bone, skeletal muscle, and in liver 5-, 2.4-, 2.4-, 2.1-, and 2-fold, respectively. As expected, nitrate reduction into nitrite was highest in liver but also substantial in skin and skeletal muscle, followed by the distribution of 15N-labeled nitrite. We believe that these results underline the major roles played by skeletal muscle, skin, and bone, the three largest organs in mammals, in maintaining NO homeostasis, especially via the nitrate\u2013nitrite\u2013NO pathway.<\/jats:p>","DOI":"10.3390\/nu16162674","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T06:02:37Z","timestamp":1723528957000},"page":"2674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Skeletal Muscle, Skin, and Bone as Three Major Nitrate Reservoirs in Mammals: Chemiluminescence and 15N-Tracer Studies in Yorkshire Pigs"],"prefix":"10.3390","volume":"16","author":[{"given":"Barbora","family":"Piknova","sequence":"first","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Won","family":"Park","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5942-4164","authenticated-orcid":false,"given":"Khalid J.","family":"Tunau-Spencer","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Jenkins","sequence":"additional","affiliation":[{"name":"MedStar Health Research Institute, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Hellinga","sequence":"additional","affiliation":[{"name":"MedStar Health Research Institute, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-398X","authenticated-orcid":false,"given":"Peter J.","family":"Walter","sequence":"additional","affiliation":[{"name":"Clinical Mass Spectrometry Core, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Cai","sequence":"additional","affiliation":[{"name":"Clinical Mass Spectrometry Core, National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan N.","family":"Schechter","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1161\/01.HYP.12.4.365","article-title":"The discovery of nitric oxide as the endogenous nitrovasodilator","volume":"12","author":"Moncada","year":"1988","journal-title":"Hypertension"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113793","DOI":"10.1016\/j.bcp.2020.113793","article-title":"Historical origins of the discovery of mammalian nitric oxide (nitrogen monoxide) production\/physiology\/pathophysiology","volume":"176","author":"Lancaster","year":"2020","journal-title":"Biochem. 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