Nitrite is an alternative source of NO in vivo.
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.
Tsuchiya
Koichiro
K
Department of Pharmacology, The University of Tokushima School of Medicine, Tokushima, Japan.
Kanematsu
Yasuhisa
Y
Yoshizumi
Masanori
M
Ohnishi
Hideki
H
Kirima
Kazuyoshi
K
Izawa
Yuki
Y
Shikishima
Michiyo
M
Ishida
Tatsuhiro
T
Kondo
Shuji
S
Kagami
Shoji
S
Takiguchi
Yoshiharu
Y
Tamaki
Toshiaki
T
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006442:Glycated Hemoglobin; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000493:pharmacokinetics*; D009587:Nitrogen Isotopes; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D009573:Nitrites; D009587:Nitrogen Isotopes; C058377:hemoglobin A, glycosylated-nitric oxide complex