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

Expired nitric oxide (NOe) varies with hemodynamic or ventilatory perturbations, possibly due to shear stress- or stretch-stimulated NO production. Since hemoglobin (Hb) binds NO, NOe changes may reflect changes in blood volume and flow. To determine the role of blood and mechanical forces, we measured NOe in anesthetized rabbits, as well as rabbit lungs perfused with buffer, red blood cells (RBCs) or Hb following changes in flow, venous pressure (P-v), and positive end-expiratory pressure (PEEP). In buffer-perfused lungs decreases in flow and P-v reduced NOe, but NOe rose when RBCs and Hb were present. These findings are consistent with changes in vascular NO production, whose detection is obscured in blood-perfused lungs by the more dominant effect of Hb NO scavenging. PEEP decreased NOe in all perfused lungs but increased NOe in live rabbits. The NOe fall with PEEP in isolated lungs is consistent with flow redistribution from alveolar septal capillaries to extra-alveolar vessels and decreased surface area or a direct, stretch-mediated 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 and systemic responses render it difficult to use NOe changes as an accurate measure of lung tissue NO production.