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.

Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis

“…Mechanisms of tissue uptake and distribution of nitrite remain poorly understood (32). However, we found distinct differences in blood and tissue nitrite levels in response to sodium nitrite therapy.…”

“…Recent reports demonstrate that administration of nitrite results in rapid accumulation of this anion in plasma and blood (32,33). Fig.…”

Radiation as a Risk Factor for Cardiovascular Disease

“…Nitrite is a major storage form of nitric oxide (NO) in blood and tissues (14). Oral nitrite reverses N G -nitro-L-arginine methyl ester-induced hypertension and serves as an alternate source of NO in vivo (91). Further, plasma nitrite levels progressively decrease with increasing cardiovascular risk (52).…”

Bioanalytical profile of the l-arginine/nitric oxide pathway and its evaluation by capillary electrophoresis

“…In bacteria intracellular nitrate concentration is regulated by active membrane transport and dentification cascades [84]. However, in hypoxic condition of upper alimentary canal bacterial conversion of dietary nitrate to nitrite may be a prevalent source of nitrite and consequently of NO for proximal tissues and entire organisms [85,86]. For example, eNOS itself may effectively reduce nitrite to NO under anoxic conditions [27], and similar biases are quite possible in other tissues.…”

“…Homologous components for nitrate/nitrite transport are largely unknown in organisms, but there is some evidence of nitrite transport via a Cl − / HCO 3 − exchanger [119] which is member of the bicarbonate transporter family (SLC4). Nevertheless, it has been shown that dietary nitrate [86,120,121] as well as symbiotic and/or pathogenic bacteria immobilized nitrate [88,[122][123][124] may play an important role in the formation of nitrite at pathogenic and normal levels and consequently in regulating NO pools in higher organisms.…”