Modulation of nitric oxide bioavailability by erythrocytes

Nitric oxide (NO) activates soluble guanylyl cyclase in smooth muscle cells to induce vasodilation in the vasculature. However, as hemoglobin (Hb) is an effective scavenger of NO and is present in high concentrations inside t he red blood cell (RBC), the bioavailability of NO would be too low to elic it soluble guanylyl cyclase activation in the presence of blood. Therefore, NO bioactivity must be preserved. Here we present evidence suggesting that the RBC participates in the preservation of No bioactivity by reducing NO influx. The NO uptake by RBCs was increased and decreased by altering the d egree of band 3 binding to the cytoskeleton. Methemoglobin and denatured he moglobin binding to the RBC membrane or cytoskeleton also were shown to con tribute to reducing the NO uptake rate of the RBC. These alterations in NO uptake by the RBC, hence the NO bioavailability, were determined to correla te with the vasodilation of isolated blood vessels. Our observations sugges t that RBC membrane and cytoskeleton associated NO-inert proteins provide a barrier for NO diffusion and thus account for the reduction in the NO upta ke rate of RBCs.