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Impact of inorganic nitrate on renal sodium excretion during saline loading in healthy adults; secondary endpoints from a randomized crossover trial.

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Title: Impact of inorganic nitrate on renal sodium excretion during saline loading in healthy adults; secondary endpoints from a randomized crossover trial.
Authors: Østergaard AM; University Clinic in Nephrology and Hypertension, Gødstrup Hospital, Herning, Denmark., Rosenbæk JB; University Clinic in Nephrology and Hypertension, Gødstrup Hospital, Herning, Denmark., Ejlersen JA; Department of Nuclear Medicine, Gødstrup Hospital, Herning, Denmark., Mose FH; University Clinic in Nephrology and Hypertension, Gødstrup Hospital, Herning, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark., Bech JN; University Clinic in Nephrology and Hypertension, Gødstrup Hospital, Herning, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark., Vrist MH; University Clinic in Nephrology and Hypertension, Gødstrup Hospital, Herning, Denmark.
Source: Physiological reports [Physiol Rep] 2026 Jun; Vol. 14 (11), pp. e70919.
Publication Type: Journal Article; Randomized Controlled Trial
Language: English
Journal Info: Publisher: published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society Country of Publication: United States NLM ID: 101607800 Publication Model: Print Cited Medium: Internet ISSN: 2051-817X (Electronic) Linking ISSN: 2051817X NLM ISO Abbreviation: Physiol Rep Subsets: MEDLINE
Imprint Name(s): Original Publication: [Malden MA] : published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society, 2013-
MeSH Terms: Nitrates*/pharmacology , Nitrates*/administration & dosage , Natriuresis*/drug effects , Sodium*/urine , Sodium*/metabolism , Potassium Compounds*/pharmacology , Potassium Compounds*/administration & dosage , Saline Solution*/administration & dosage , Kidney*/drug effects , Kidney*/metabolism, Cyclic GMP/blood ; Nitric Oxide/blood ; Blood Pressure/drug effects ; Humans ; Cross-Over Studies ; Male ; Female ; Adult ; Double-Blind Method ; Young Adult
Abstract: Inorganic nitrate may lower blood pressure (BP) and enhance natriuresis through nitric oxide (NO) mediated mechanisms. Studies have found inconsistent effects of NO on sodium excretion. Nitric oxide synthase (NOS) inhibition suggests increased NO promotes natriuresis, whereas inorganic nitrate studies remain inconclusive. We conducted a randomized, double-blind, placebo-controlled crossover trial in 18 healthy adults, with 4 days of potassium nitrate (KNO3) or placebo before 1 L isotonic saline infusion. BP, hemodynamic markers of the NO system, and renal function were measured. After saline GFR, renal water and sodium handling did not significantly differ between KNO3 and placebo (KCl). Central diastolic BP was modestly higher during KNO3 (p = 0.023). Brachial systolic BP did not differ (p = 0.052); however, systolic BP was higher during KNO3 after 120 min (Sidak adjusted, p = 0.030). Plasma levels of the second messenger of NO, cyclic guanosine monophosphate (cGMP), were lower after saline during KNO3 (p = 0.012). Short-term KNO3 did not induce a natriuretic response during acute saline loading. KNO3 was associated with a small increase in central diastolic BP and lower plasma cGMP levels. These findings suggest that high-dose KNO3 exposure may affect the endogenous NO response.
(© 2026 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
References: Neurosci Lett. 1994 Jan 3;165(1-2):48-50. (PMID: 7517025)
Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1658-62. (PMID: 15191897)
J Clin Invest. 2007 Sep;117(9):2583-91. (PMID: 17717604)
Eur J Clin Pharmacol. 1984;26(5):543-7. (PMID: 6468469)
BMC Nephrol. 2013 Sep 26;14:202. (PMID: 24067081)
Cell Signal. 2011 Dec;23(12):1921-6. (PMID: 21914472)
Semin Nephrol. 1999 May;19(3):242-50. (PMID: 10226330)
Antioxid Redox Signal. 2015 Aug 1;23(4):295-306. (PMID: 24224525)
Am J Physiol. 1996 May;270(5 Pt 2):F845-51. (PMID: 8928847)
Acta Physiol (Oxf). 2020 May;229(1):e13443. (PMID: 31944587)
Hypertension. 2015 Feb;65(2):320-7. (PMID: 25421976)
BMC Nephrol. 2014 Jun 25;15:100. (PMID: 24965902)
Circulation. 2004 Jan 20;109(2):172-7. (PMID: 14662708)
Nitric Oxide. 2023 May 1;134-135:1-9. (PMID: 36906115)
Acta Physiol Scand. 1982 Sep;116(1):75-81. (PMID: 6818840)
Hypertension. 2010 Aug;56(2):274-81. (PMID: 20585108)
Clin Exp Pharmacol Physiol. 1992 Sep;19(9):619-25. (PMID: 1327594)
Eur J Clin Invest. 1993 Jun;23(6):375-81. (PMID: 8393795)
Endocrinology. 1993 Sep;133(3):1466-9. (PMID: 7689960)
Br J Clin Pharmacol. 2015 Sep;80(3):425-35. (PMID: 25778445)
Am J Physiol Renal Physiol. 2001 May;280(5):F860-7. (PMID: 11292629)
Clin Physiol Funct Imaging. 2021 Nov;41(6):488-496. (PMID: 34418886)
Circ Res. 2014 May 23;114(11):1804-14. (PMID: 24855203)
BMC Nephrol. 2014 Jun 26;15:101. (PMID: 24970686)
Neuroendocrinology. 1993 May;57(5):955-9. (PMID: 8413832)
Am J Physiol. 1994 Feb;266(2 Pt 2):H822-8. (PMID: 7511350)
Clin Exp Hypertens. 2012;34(8):567-74. (PMID: 22559218)
BMC Nephrol. 2019 Jun 3;20(1):200. (PMID: 31159750)
Biophys J. 2016 Jul 12;111(1):208-21. (PMID: 27410748)
Hypertension. 1994 Jun;23(6 Pt 2):951-6. (PMID: 8206634)
Physiol Rep. 2021 Jan;8(24):e14653. (PMID: 33356004)
Circ Res. 1993 Nov;73(5):808-12. (PMID: 7691429)
Nutr Metab Cardiovasc Dis. 2023 Jun;33(6):1263-1267. (PMID: 36958967)
Physiologist. 1984;27(6 Suppl):S51-2. (PMID: 11539013)
Contributed Indexing: Keywords: arginine vasopressin; hemodynamic; inorganic nitrate; nitric oxide; renal sodium excretion; saline loading
Substance Nomenclature: 0 (Nitrates)
H2D2X058MU (Cyclic GMP)
9NEZ333N27 (Sodium)
RU45X2JN0Z (potassium nitrate)
0 (Potassium Compounds)
31C4KY9ESH (Nitric Oxide)
0 (Saline Solution)
Entry Date(s): Date Created: 20260604 Date Completed: 20260610 Latest Revision: 20260918
Update Code: 20260918
PubMed Central ID: PMC13581089
DOI: 10.14814/phy2.70919
PMID: 42237694
Database: MEDLINE
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  Data: Impact of inorganic nitrate on renal sodium excretion during saline loading in healthy adults; secondary endpoints from a randomized crossover trial.
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  Data: <searchLink fieldCode="AU" term="%22Østergaard+AM%22">Østergaard AM</searchLink>; University Clinic in Nephrology and Hypertension, Gødstrup Hospital, Herning, Denmark.<br /><searchLink fieldCode="AU" term="%22Rosenbæk+JB%22">Rosenbæk JB</searchLink>; University Clinic in Nephrology and Hypertension, Gødstrup Hospital, Herning, Denmark.<br /><searchLink fieldCode="AU" term="%22Ejlersen+JA%22">Ejlersen JA</searchLink>; Department of Nuclear Medicine, Gødstrup Hospital, Herning, Denmark.<br /><searchLink fieldCode="AU" term="%22Mose+FH%22">Mose FH</searchLink>; University Clinic in Nephrology and Hypertension, Gødstrup Hospital, Herning, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark.<br /><searchLink fieldCode="AU" term="%22Bech+JN%22">Bech JN</searchLink>; University Clinic in Nephrology and Hypertension, Gødstrup Hospital, Herning, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark.<br /><searchLink fieldCode="AU" term="%22Vrist+MH%22">Vrist MH</searchLink>; University Clinic in Nephrology and Hypertension, Gødstrup Hospital, Herning, Denmark.
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  Data: <i>Original Publication</i>: [Malden MA] : published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society, 2013-
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– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Inorganic nitrate may lower blood pressure (BP) and enhance natriuresis through nitric oxide (NO) mediated mechanisms. Studies have found inconsistent effects of NO on sodium excretion. Nitric oxide synthase (NOS) inhibition suggests increased NO promotes natriuresis, whereas inorganic nitrate studies remain inconclusive. We conducted a randomized, double-blind, placebo-controlled crossover trial in 18 healthy adults, with 4 days of potassium nitrate (KNO<subscript>3</subscript>) or placebo before 1 L isotonic saline infusion. BP, hemodynamic markers of the NO system, and renal function were measured. After saline GFR, renal water and sodium handling did not significantly differ between KNO<subscript>3</subscript> and placebo (KCl). Central diastolic BP was modestly higher during KNO<subscript>3</subscript> (p = 0.023). Brachial systolic BP did not differ (p = 0.052); however, systolic BP was higher during KNO<subscript>3</subscript> after 120 min (Sidak adjusted, p = 0.030). Plasma levels of the second messenger of NO, cyclic guanosine monophosphate (cGMP), were lower after saline during KNO<subscript>3</subscript> (p = 0.012). Short-term KNO<subscript>3</subscript> did not induce a natriuretic response during acute saline loading. KNO<subscript>3</subscript> was associated with a small increase in central diastolic BP and lower plasma cGMP levels. These findings suggest that high-dose KNO<subscript>3</subscript> exposure may affect the endogenous NO response.<br /> (© 2026 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
– Name: Ref
  Label: References
  Group: RefInfo
  Data: Neurosci Lett. 1994 Jan 3;165(1-2):48-50. (PMID: <searchLink fieldCode="PM" term="%227517025%22">7517025)</searchLink><br />Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1658-62. (PMID: <searchLink fieldCode="PM" term="%2215191897%22">15191897)</searchLink><br />J Clin Invest. 2007 Sep;117(9):2583-91. (PMID: <searchLink fieldCode="PM" term="%2217717604%22">17717604)</searchLink><br />Eur J Clin Pharmacol. 1984;26(5):543-7. (PMID: <searchLink fieldCode="PM" term="%226468469%22">6468469)</searchLink><br />BMC Nephrol. 2013 Sep 26;14:202. (PMID: <searchLink fieldCode="PM" term="%2224067081%22">24067081)</searchLink><br />Cell Signal. 2011 Dec;23(12):1921-6. (PMID: <searchLink fieldCode="PM" term="%2221914472%22">21914472)</searchLink><br />Semin Nephrol. 1999 May;19(3):242-50. (PMID: <searchLink fieldCode="PM" term="%2210226330%22">10226330)</searchLink><br />Antioxid Redox Signal. 2015 Aug 1;23(4):295-306. (PMID: <searchLink fieldCode="PM" term="%2224224525%22">24224525)</searchLink><br />Am J Physiol. 1996 May;270(5 Pt 2):F845-51. (PMID: <searchLink fieldCode="PM" term="%228928847%22">8928847)</searchLink><br />Acta Physiol (Oxf). 2020 May;229(1):e13443. (PMID: <searchLink fieldCode="PM" term="%2231944587%22">31944587)</searchLink><br />Hypertension. 2015 Feb;65(2):320-7. (PMID: <searchLink fieldCode="PM" term="%2225421976%22">25421976)</searchLink><br />BMC Nephrol. 2014 Jun 25;15:100. (PMID: <searchLink fieldCode="PM" term="%2224965902%22">24965902)</searchLink><br />Circulation. 2004 Jan 20;109(2):172-7. (PMID: <searchLink fieldCode="PM" term="%2214662708%22">14662708)</searchLink><br />Nitric Oxide. 2023 May 1;134-135:1-9. (PMID: <searchLink fieldCode="PM" term="%2236906115%22">36906115)</searchLink><br />Acta Physiol Scand. 1982 Sep;116(1):75-81. (PMID: <searchLink fieldCode="PM" term="%226818840%22">6818840)</searchLink><br />Hypertension. 2010 Aug;56(2):274-81. (PMID: <searchLink fieldCode="PM" term="%2220585108%22">20585108)</searchLink><br />Clin Exp Pharmacol Physiol. 1992 Sep;19(9):619-25. (PMID: <searchLink fieldCode="PM" term="%221327594%22">1327594)</searchLink><br />Eur J Clin Invest. 1993 Jun;23(6):375-81. (PMID: <searchLink fieldCode="PM" term="%228393795%22">8393795)</searchLink><br />Endocrinology. 1993 Sep;133(3):1466-9. (PMID: <searchLink fieldCode="PM" term="%227689960%22">7689960)</searchLink><br />Br J Clin Pharmacol. 2015 Sep;80(3):425-35. (PMID: <searchLink fieldCode="PM" term="%2225778445%22">25778445)</searchLink><br />Am J Physiol Renal Physiol. 2001 May;280(5):F860-7. (PMID: <searchLink fieldCode="PM" term="%2211292629%22">11292629)</searchLink><br />Clin Physiol Funct Imaging. 2021 Nov;41(6):488-496. (PMID: <searchLink fieldCode="PM" term="%2234418886%22">34418886)</searchLink><br />Circ Res. 2014 May 23;114(11):1804-14. (PMID: <searchLink fieldCode="PM" term="%2224855203%22">24855203)</searchLink><br />BMC Nephrol. 2014 Jun 26;15:101. (PMID: <searchLink fieldCode="PM" term="%2224970686%22">24970686)</searchLink><br />Neuroendocrinology. 1993 May;57(5):955-9. (PMID: <searchLink fieldCode="PM" term="%228413832%22">8413832)</searchLink><br />Am J Physiol. 1994 Feb;266(2 Pt 2):H822-8. (PMID: <searchLink fieldCode="PM" term="%227511350%22">7511350)</searchLink><br />Clin Exp Hypertens. 2012;34(8):567-74. (PMID: <searchLink fieldCode="PM" term="%2222559218%22">22559218)</searchLink><br />BMC Nephrol. 2019 Jun 3;20(1):200. (PMID: <searchLink fieldCode="PM" term="%2231159750%22">31159750)</searchLink><br />Biophys J. 2016 Jul 12;111(1):208-21. (PMID: <searchLink fieldCode="PM" term="%2227410748%22">27410748)</searchLink><br />Hypertension. 1994 Jun;23(6 Pt 2):951-6. (PMID: <searchLink fieldCode="PM" term="%228206634%22">8206634)</searchLink><br />Physiol Rep. 2021 Jan;8(24):e14653. (PMID: <searchLink fieldCode="PM" term="%2233356004%22">33356004)</searchLink><br />Circ Res. 1993 Nov;73(5):808-12. (PMID: <searchLink fieldCode="PM" term="%227691429%22">7691429)</searchLink><br />Nutr Metab Cardiovasc Dis. 2023 Jun;33(6):1263-1267. (PMID: <searchLink fieldCode="PM" term="%2236958967%22">36958967)</searchLink><br />Physiologist. 1984;27(6 Suppl):S51-2. (PMID: <searchLink fieldCode="PM" term="%2211539013%22">11539013)</searchLink>
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  Data: <i>Keywords: </i>arginine vasopressin; hemodynamic; inorganic nitrate; nitric oxide; renal sodium excretion; saline loading
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              Text: 2026 Jun
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          Titles:
            – TitleFull: Physiological reports
              Type: main
ResultId 1