Nitrite is an alternative source of NO in vivo
Abstract
In this study, we investigated whether orally administered nitrite is changed to NO and whether nitrite attenuates hypertension in a dose-dependent manner. We utilized a stable isotope of [15N]nitrite (15NO2-) as a source of nitrite to distinguish between endogenous nitrite and that exogenously administered and measured hemoglobin (Hb)-NO as an index of circulating NO in whole blood using electron paramagnetic resonance (EPR) spectroscopy. When 1 mg/kg Na15NO2 was orally administered to rats, an apparent EPR signal derived from Hb15NO (A(Z) = 23.4 gauss) appeared in the blood. The peak blood HbNO concentration occurred at the first measurement after intake (5 min) for treatment with 1 and 3 mg/kg (HbNO: 4.93 +/- 0.52 and 10.58 +/- 0.40 microM, respectively) and at 15 min with 10 mg/kg (HbNO: 38.27 +/- 9.23 microM). In addition, coadministration of nitrite (100 mg/l drinking water) with N(omega)-nitro-L-arginine methyl ester (L-NAME; 1 g/l) for 3 wk significantly attenuated the L-NAME-induced hypertension (149 +/- 10 mmHg) compared with L-NAME alone (170 +/- 13 mmHg). Furthermore, this phenomenon was associated with an increase in circulating HbNO. Our findings clearly indicate that orally ingested nitrite can be an alternative to L-arginine as a source of NO in vivo and may explain, at least in part, the mechanism of the nitrite/nitrate-rich Dietary Approaches to Stop Hypertension diet-induced hypotensive effects.
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Tsuchiya et al. showed that nitrite attenuated the increases in blood pressure caused by L-NAME, an inhibitor of NO synthases.
“In parallel with these findings, Tsuchiya et al. showed that nitrite attenuated the increases in blood pressure caused by L-NAME, an inhibitor of NO synthases [46].”
From Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension (2011) · cites this paper as [46]
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“It had been believed that ingested nitrite is absorbed by the gastrointestinal tract (51) or reacts in the stomach with secondary or tertiary amines and amides present in foods such as cheese or meat to form N-nitroso compounds (7).”
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Montenegro, M. F., Pinheiro, L. C., Amaral, J. H., Ferreira, G. C., Portella, R. L., & Tanus-Santos, J. E. (2014) · Nitric Oxide · doi:10.1016/j.niox.2014.09.103 · Cited by 7 · see citing works
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Arnold, J. T., Lloyd, A. B., Bailey, S. J., Fujimoto, T., Matsutake, R., Takayanagi, M., Nishiyasu, T., & Fujii, N. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00487.2020 · Cited by 7 · see citing works
- Authors
- Tsuchiya, K., Kanematsu, Y., Yoshizumi, M., Ohnishi, H., Kirima, K., Izawa, Y., Shikishima, M., Ishida, T., Kondo, S., Kagami, S., Takiguchi, Y., & Tamaki, T.
- Affiliations
- Tokushima University (JP)
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2005-05
- Volume
- 288
- Issue
- 5
- Pages
- H2163-H2170
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2125647807
- Cited by
- 127
- References
- 99
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 4 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 9 · 2016: 6 · 2015: 4 · 2014: 5 · 2013: 2 · 2012: 9
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- nitrite, nitric oxide, L-NAME-induced hypertension, nitric oxide synthase inhibition, dietary nitrate, DASH diet, L-arginine, blood pressure
- MeSH terms
- Administration, Oral, Animals, Blood Pressure, Electron Spin Resonance Spectroscopy, Enzyme Inhibitors, Glycated Hemoglobin, Hypertension, Male, Nitric Oxide, Nitrites, Nitrogen Isotopes, Rats, Sprague-Dawley, NG-Nitroarginine Methyl Ester, Rats
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