RESUMEN
BACKGROUND AND PURPOSE: Nitrite (NO2â») has recently been shown to represent a potential source of NO, in particular under hypoxic conditions. The aim of the current study was to compare the haemodynamic effects of NO2â» in healthy volunteers and patients with stable congestive heart failure (CHF). EXPERIMENTAL APPROACH: The acute haemodynamic effects of brachial artery infusion of NO2â» (0.31 to 7.8 µmol·min⻹) was assessed in normal subjects (n = 20) and CHF patients (n = 21). KEY RESULTS: NO2â» infusion was well tolerated in all subjects. Forearm blood flow (FBF) increased markedly in CHF patients at NO2â» infusion rates which induced no changes in normal subjects (ANOVA: F = 5.5; P = 0.02). Unstressed venous volume (UVV) increased even with the lowest NO2â» infusion rate in all subjects (indicating venodilation), with CHF patients being relatively hyporesponsive compared with normal subjects (ANOVA: F = 6.2; P = 0.01). There were no differences in venous blood pH or oxygen concentration between groups or during NO2â» infusion. Venous plasma NO2â» concentrations were lower in CHF patients at baseline, and rose substantially less with NO2â» infusion, without incremental oxidative generation of nitrate, consistent with accelerated clearance in these patients. Plasma protein-bound NO concentrations were lower in CHF patients than normal subjects at baseline. This difference was attenuated during NO2â» infusion. Prolonged NO2â» exposure in vivo did not induce oxidative stress, nor did it induce tolerance in vitro. CONCLUSIONS AND IMPLICATIONS: The findings of arterial hyper-responsiveness to infused NO2â» in CHF patients, with evidence of accelerated transvascular NO2â» clearance (presumably with concomitant NO release) suggests that NO2â» effects may be accentuated in such patients. These findings provide a stimulus for the clinical exploration of NO2â» as a therapeutic modality in CHF.