Nitrite is an alternative source of NO in vivo

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 288; no. 5; pp. H2163 - H2170
• Main Authors: Tsuchiya, Koichiro, Kanematsu, Yasuhisa, Yoshizumi, Masanori, Ohnishi, Hideki, Kirima, Kazuyoshi, Izawa, Yuki, Shikishima, Michiyo, Ishida, Tatsuhiro, Kondo, Shuji, Kagami, Shoji, Takiguchi, Yoshiharu, Tamaki, Toshiaki
• Format: Journal Article
• Language: English
• Published: United States 01.05.2005
• Subjects: Administration, Oral; Animals; Blood Pressure - drug effects; Blood Pressure - physiology; Electron Spin Resonance Spectroscopy; Enzyme Inhibitors - pharmacology; Glycated Hemoglobin A; Hypertension - metabolism; Male; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - blood; Nitrites - pharmacokinetics; Nitrogen Isotopes; Rats; Rats, Sprague-Dawley
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00525.2004

1 Department of Pharmacology and 2 Department of Pediatrics, The University of Tokushima School of Medicine, and 3 Department of Clinical Pharmacology and 4 Department 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 [ 15 N]nitrite ( 15 NO 2 – ) 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 Na 15 NO 2 was orally administered to rats, an apparent EPR signal derived from Hb 15 NO ( 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 Address for reprint requests and other correspondence: T. Tamaki, Dept. of Pharmacology, The Univ. of Tokushima School of Medicine, Tokushima 770-8503, Japan (E-mail: tamaki{at}basic.med.tokushima-u.ac.jp )