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 Na15NO2was orally administered to rats, an apparent EPR signal derived from Hb15NO ( AZ= 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 Nω-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.