Study on the Relationship Between Plasma Nitrite and Nitrate Level and Salt Sensitivity in Human Hypertension: Modulation of Nitric Oxide Synthesis by Salt Intake
Abstract
Background —High salt intake suppresses the effect of nitric oxide (NO) in the peripheral resistance vessels in animal models. We tested the hypothesis that the modulation of endogenous NO is related to salt sensitivity in human hypertension. Methods and Results —Inpatients with essential hypertension (n=24) were maintained on a normal-salt diet (12 g/d NaCl) for 3 days, a low-salt diet (2 g), a high-salt diet (20 to 23 g), and a low-salt diet for 7 days. Normotensive subjects (n=16) were maintained on the first 2 salt diets. The hypertensive patients whose average 24-hour blood pressure was increased by >5% by salt loading were assigned to group 1 (n=8) and the others to group 2 (n=16). Nitrate plus nitrite (NO x ) was measured by the Griess method, and asymmetrical dimethylarginine (ADMA) by high-performance liquid chromatography. The plasma NO x level during the normal-salt diet was lower in group 1 than in group 2 and the normotensive group. After salt loading, the plasma NO x level was decreased and reversed after the second salt restriction. Plasma ADMA level was increased after salt loading and decreased after salt restriction. The change in plasma NO x level was correlated inversely with those in blood pressure ( r =−0.59, P =0.0007) and plasma ADMA level ( r =−0.64, P =0.003) after salt loading and restriction. Conclusions —Modulation of NO synthesis by salt intake may be involved in a mechanism for salt sensitivity in human hypertension, presumably via the change in ADMA.
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Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704 · see citing works
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Asymmetrical Dimethylarginine: The Über Marker?
Cooke, J. P. (2004) · Circulation · doi:10.1161/01.cir.0000126823.07732.d5 · Cited by 396 · see citing works
Date Fruits ( <i>Phoenix dactylifera</i> Linn): An Emerging Medicinal Food
Vayalil, P. K. (2012) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2010.499824 · Cited by 323 · see citing works
Dietary Therapy in Hypertension
Sacks, F. M., & Campos, H. (2010) · New England Journal of Medicine · doi:10.1056/nejmct0911013 · Cited by 250 · see citing works
Endothelial dysfunction in salt-sensitive essential hypertension
Bragulat, E., de la Sierra, A., Antonio, M. T., & Coca, A. (2001) · Hypertension · doi:10.1161/01.hyp.37.2.444 · Cited by 172 · see citing works
Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care
Weitzberg, E., Hezel, M., Lundberg, J. O., & Warner, D. S. (2010) · Anesthesiology · doi:10.1097/aln.0b013e3181fcf3cc · Cited by 145 · see citing works
Morris, R. C., Schmidlin, O., Sebastian, A., Tanaka, M., & Kurtz, T. W. (2016) · Circulation · doi:10.1161/circulationaha.115.017923 · Cited by 123 · see citing works
Low-sodium DASH reduces oxidative stress and improves vascular function in salt-sensitive humans
Al-Solaiman, Y., Jesri, A., Zhao, Y., Morrow, J. D., & Egan, B. M. (2009) · Journal of Human Hypertension · doi:10.1038/jhh.2009.32 · Cited by 102 · see citing works
Schmidlin, O., Forman, A., Leone, A., Sebastian, A., & Morris, R. C. (2011) · Hypertension · doi:10.1161/hypertensionaha.111.170175 · Cited by 82 · see citing works
An Appraisal of Methods Recently Recommended for Testing Salt Sensitivity of Blood Pressure
Kurtz, T. W., DiCarlo, S. E., Pravenec, M., & Morris, R. C. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.005653 · Cited by 64 · see citing works
Rassaf, T., Ferdinandy, P., & Schulz, R. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12291 · Cited by 62 · see citing works
Kurtz, T. W., DiCarlo, S. E., Pravenec, M., & Morris, R. C. (2017) · Journal of Hypertension · doi:10.1097/hjh.0000000000001458 · Cited by 42 · see citing works
Notsu, Y., Nabika, T., Bokura, H., Suyama, Y., Kobayashi, S., Yamaguchi, S., & Masuda, J. (2009) · American Journal of Hypertension · doi:10.1038/ajh.2008.346 · Cited by 36 · see citing works
Cakir, E., Ozcan, O., Yaman, H., Akgul, E. O., Bilgi, C., Erbil, M. K., & Yesilova, Z. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-2045 · Cited by 28 · see citing works
Association between arterial properties and renal sodium handling in a general population.
Seidlerová, J., Staessen, J. A., Maillard, M., Nawrot, T., Zhang, H., Bochud, M., Kuznetsova, T., Richart, T., Van Bortel, L. M., Struijker-Boudier, H. A., et al. (2006) · Hypertension · doi:10.1161/01.hyp.0000240516.60040.ba · Cited by 25 · see citing works
- Authors
- Fujiwara, N., Osanai, T., Kamada, T., Katoh, T., Takahashi, K., & Okumura, K.
- Affiliations
- Hirosaki University (JP)
- Venue
- Circulation
- Published
- 2000-02-29
- Volume
- 101
- Issue
- 8
- Pages
- 856-861
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2114290793
- Cited by
- 242
- References
- 1
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 1 · 2019: 4 · 2018: 8 · 2017: 7 · 2016: 6 · 2015: 12 · 2014: 9 · 2013: 11 · 2012: 7
- FWCI
- 14.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Circulation
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- plasma nitrite, plasma nitrate, salt sensitivity, essential hypertension, nitric oxide, asymmetric dimethylarginine, salt loading, salt restriction, dietary sodium, blood pressure, nitric oxide production
- MeSH terms
- Adult, Aged, Arginine, Blood Pressure, Electrolytes, Female, Humans, Hypertension, Lipids, Male, Middle Aged, Nitrates, Nitric Oxide, Nitrites, Norepinephrine, Renin, Smoking, Vascular Resistance, Sodium Chloride, Dietary
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