Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action

AUTOR(ES)

Lauer, Thomas

FONTE

The National Academy of Sciences

RESUMO

The plasma level of NOx, i.e., the sum of NO2− and NO3−, is frequently used to assess NO bioavailability in vivo. However, little is known about the kinetics of NO conversion to these metabolites under physiological conditions. Moreover, plasma nitrite recently has been proposed to represent a delivery source for intravascular NO. We therefore sought to investigate in humans whether changes in NOx concentration are a reliable marker for endothelial NO production and whether physiological concentrations of nitrite are vasoactive. NO2− and NO3− concentrations were measured in blood sampled from the antecubital vein and brachial artery of 24 healthy volunteers. No significant arterial-venous gradient was observed for either NO2− or NO3−. Endothelial NO synthase (eNOS) stimulation with acetylcholine (1–10 μg/min) dose-dependently augmented venous NO2− levels by maximally 71%. This effect was paralleled by an almost 4-fold increase in forearm blood flow (FBF), whereas an equieffective dose of papaverine produced no change in venous NO2−. Intraarterial infusion of NO2− had no effect on FBF. NOS inhibition (NG-monomethyl-l-arginine; 4–12 μmol/min) dose-dependently reduced basal NO2− and FBF and blunted acetylcholine-induced vasodilation and NO release by more than 80% and 90%, respectively. In contrast, venous NO3− and total NOx remained unchanged as did systemic arterial NO2− and NO3− levels during all these interventions. FBF and NO release showed a positive association (r = 0.85; P < 0.001). These results contradict the current paradigm that plasma NO3− and/or total NOx are generally useful markers of endogenous NO production and demonstrate that only NO2− reflects acute changes in regional eNOS activity. Our results further demonstrate that physiological levels of nitrite are vasodilator-inactive.

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