{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:24:20Z","timestamp":1763389460329,"version":"3.40.5"},"reference-count":76,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council of Australia","award":["1164128 and 1138533"],"award-info":[{"award-number":["1164128 and 1138533"]}]},{"name":"PKD Australia"},{"name":"University of Sydney, Research Training Program Stipend"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Augmentation of endogenous nitric oxide (NO) synthesis, either by the classical L-arginine-NO synthase pathway, or the recently discovered entero-salivary nitrate-nitrite-NO system, may slow the progression of autosomal dominant polycystic kidney disease (ADPKD). To test this hypothesis, the expression of NO in human ADPKD cell lines (WT 9\u20137, WT 9\u201312), and the effect of L-arginine on an<jats:italic>in vitro<\/jats:italic>model of three-dimensional cyst growth using MDCK cells, was examined. In addition, groups of homozygous<jats:italic>Pkd1<\/jats:italic><jats:sup><jats:italic>RC\/RC<\/jats:italic><\/jats:sup>mice (a hypomorphic genetic ortholog of ADPKD) received either low, moderate or high dose sodium nitrate (0.1, 1 or 10 mmol\/kg\/day), or sodium chloride (vehicle; 10 mmol\/kg\/day), supplemented drinking water from postnatal month 1 to 9 (n = 12 per group).<jats:italic>In vitro<\/jats:italic>, intracellular NO, as assessed by DAF-2\/DA fluorescence, was reduced by &gt;70% in human ADPKD cell lines, and L-arginine and the NO donor, sodium nitroprusside, both attenuated<jats:italic>in vitro<\/jats:italic>cyst growth by up to 18%. In contrast, in<jats:italic>Pkd1<\/jats:italic><jats:sup><jats:italic>RC\/RC<\/jats:italic><\/jats:sup>mice, sodium nitrate supplementation increased serum nitrate\/nitrite levels by ~25-fold in the high dose group (P&lt;0.001), but kidney enlargement and percentage cyst area was not altered, regardless of dose. In conclusion, L-arginine has mild direct efficacy on reducing renal cyst growth<jats:italic>in vitro<\/jats:italic>, whereas long-term sodium nitrate supplementation was ineffective<jats:italic>in vivo<\/jats:italic>. These data suggest that the bioconversion of dietary nitrate to NO by the entero-salivary pathway may not be sufficient to influence the progression of renal cyst growth in ADPKD.<\/jats:p>","DOI":"10.1371\/journal.pone.0248400","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T19:24:05Z","timestamp":1619119445000},"page":"e0248400","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3269-3801","authenticated-orcid":true,"given":"Jennifer Q. 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