Hemoglobin and red blood cells alter the response of expired nitric oxide to mechanical forces

Expired nitric oxide (NOe) varies with hemodynamic or ventilatory perturbat ions, possibly due to shear stress- or stretch-stimulated NO production. Si nce hemoglobin (Hb) binds NO, NOe changes may reflect changes in blood volu me and flow. To determine the role of blood and mechanical forces, we measu red NOe in anesthetized rabbits, as well as rabbit lungs perfused with buff er, red blood cells (RBCs) or Hb following changes in flow, venous pressure (P-v), and positive end-expiratory pressure (PEEP). In buffer-perfused lun gs decreases in flow and P-v reduced NOe, but NOe rose when RBCs and Hb wer e present. These findings are consistent with changes in vascular NO produc tion, whose detection is obscured in blood-perfused lungs by the more domin ant effect of Hb NO scavenging. PEEP decreased NOe in all perfused lungs bu t increased NOe in live rabbits. The NOe fall with PEEP in isolated lungs i s consistent with flow redistribution from alveolar septal capillaries to e xtra-alveolar vessels and decreased surface area or a direct, stretch-media ted depression of lung epithelial NO production. In live rabbits, increased NOe may reflect blood flow reduction and decreased Hb NO scavenging and/or autonomic responses that increase NO production. We conclude that blood an d systemic responses render it difficult to use NOe changes as an accurate measure of lung tissue NO production.