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Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease
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 express...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061912/ https://www.ncbi.nlm.nih.gov/pubmed/33886581 http://dx.doi.org/10.1371/journal.pone.0248400 |
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author | Zhang, Jennifer Q. J. Saravanabavan, Sayanthooran Cheng, Kai Man Raghubanshi, Aarya Chandra, Ashley N. Munt, Alexandra Rayner, Benjamin Zhang, Yunjia Chau, Katrina Wong, Annette T. Y. Rangan, Gopala K. |
author_facet | Zhang, Jennifer Q. J. Saravanabavan, Sayanthooran Cheng, Kai Man Raghubanshi, Aarya Chandra, Ashley N. Munt, Alexandra Rayner, Benjamin Zhang, Yunjia Chau, Katrina Wong, Annette T. Y. Rangan, Gopala K. |
author_sort | Zhang, Jennifer Q. J. |
collection | PubMed |
description | 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 9–7, WT 9–12), and the effect of L-arginine on an in vitro model of three-dimensional cyst growth using MDCK cells, was examined. In addition, groups of homozygous Pkd1(RC/RC) 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). In vitro, intracellular NO, as assessed by DAF-2/DA fluorescence, was reduced by >70% in human ADPKD cell lines, and L-arginine and the NO donor, sodium nitroprusside, both attenuated in vitro cyst growth by up to 18%. In contrast, in Pkd1(RC/RC) mice, sodium nitrate supplementation increased serum nitrate/nitrite levels by ~25-fold in the high dose group (P<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 in vitro, whereas long-term sodium nitrate supplementation was ineffective in vivo. 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. |
format | Online Article Text |
id | pubmed-8061912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-80619122021-05-04 Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease Zhang, Jennifer Q. J. Saravanabavan, Sayanthooran Cheng, Kai Man Raghubanshi, Aarya Chandra, Ashley N. Munt, Alexandra Rayner, Benjamin Zhang, Yunjia Chau, Katrina Wong, Annette T. Y. Rangan, Gopala K. PLoS One Research Article 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 9–7, WT 9–12), and the effect of L-arginine on an in vitro model of three-dimensional cyst growth using MDCK cells, was examined. In addition, groups of homozygous Pkd1(RC/RC) 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). In vitro, intracellular NO, as assessed by DAF-2/DA fluorescence, was reduced by >70% in human ADPKD cell lines, and L-arginine and the NO donor, sodium nitroprusside, both attenuated in vitro cyst growth by up to 18%. In contrast, in Pkd1(RC/RC) mice, sodium nitrate supplementation increased serum nitrate/nitrite levels by ~25-fold in the high dose group (P<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 in vitro, whereas long-term sodium nitrate supplementation was ineffective in vivo. 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. Public Library of Science 2021-04-22 /pmc/articles/PMC8061912/ /pubmed/33886581 http://dx.doi.org/10.1371/journal.pone.0248400 Text en © 2021 Zhang et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Zhang, Jennifer Q. J. Saravanabavan, Sayanthooran Cheng, Kai Man Raghubanshi, Aarya Chandra, Ashley N. Munt, Alexandra Rayner, Benjamin Zhang, Yunjia Chau, Katrina Wong, Annette T. Y. Rangan, Gopala K. Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease |
title | Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease |
title_full | Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease |
title_fullStr | Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease |
title_full_unstemmed | Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease |
title_short | Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease |
title_sort | long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061912/ https://www.ncbi.nlm.nih.gov/pubmed/33886581 http://dx.doi.org/10.1371/journal.pone.0248400 |
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