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This Article Full Text Full Text (PDF) All Versions of this Article: 288/5/H2163    most recent 00525.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Tsuchiya, K. Articles by Tamaki, T. Search for Related Content PubMed PubMed Citation Articles by Tsuchiya, K. Articles by Tamaki, T.

Nitrite is an alternative source of NO in vivo

¹Department of Pharmacology and ²Department of Pediatrics, The University of Tokushima School of Medicine, and ³Department of Clinical Pharmacology and ⁴Department of Pharmacokinetics and Biopharmaceutics, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan

Submitted 2 June 2004 ; accepted in final form 22 December 2004

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 µM, respectively) and at 15 min with 10 mg/kg (HbNO: 38.27 ± 9.23 µM). In addition, coadministration of nitrite (100 mg/l drinking water) with N-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.

nitric oxide; hypertension; electron paramagnetic resonance

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