Intravascular flow decreases erythrocyte consumption of nitric oxide

Nitric oxide (NO) produced by the endothelium diffuses both into the lumen and to the smooth muscle cells according to the concentration gradient in e ach direction. The extremely high reaction rate between NO and hemoglobin ( Hb), k(Hb) = 3-5 x 10(7) M-1 . s(-1), suggests that most of the NO produced would be consumed by Hb in the red blood cells (RBCs), which then would bl ock the biological effect of NO. Therefore, specific mechanisms must exist under physiological conditions to reduce the NO consumption by RBCs, in whi ch the Hb concentration is very high (24 mM heme), By using isolated microv essels as a bioassay, here we show that physiological concentrations of RBC s in the presence of intravascular flow does not inhibit NO-mediated vessel dilation, suggesting that RBCs under this condition are not an NO scavenge r. On the other hand, RBCs (50% hematocrit) without intravascular flow redu ce NO-mediated dilation to serotonin by 30%. In contrast, free Hb (10 mu M) completely inhibits NO-mediated dilation with or without intravascular flo w. The effect of flow on NO consumption by RBCs may be attributed to the fo rmation of an RBC-free zone near the vessel wall, which is caused by hydrod ynamic forces on particles. Intravascular flow does not affect the reaction rate between NO and free Hb in the lumen, because the latter forms a homog eneous solution and is not subject to the hydrodynamic separation. However, intravascular flow only partially contributes to the reduced consumption o f NO by RBCs, because without the flow, the NO consumption by RBCs is alrea dy about 3 orders of magnitude slower than free Hb.