The deformability is an important cellular feature of red blood cells (RBCs), which ultimately ensures the oxygen supply to the muscles. RBC deformability depends on nitric oxide (NO) availability in the cell. NO is enzymatically produced by NO-synthases (NOS) and in RBCs NO is generated via RBC-NOS. Still, the link between RBC-NOS dependent NO production, the cellular target of this NO, and the influence of this NO on RBC deformability is missing. Therefore, the aim of this study was to elucidate the relation between RBC-NOS activity and deformability. Blood of ten male subjects was incubated with either PBS (control) or wortmannin (inhibits RBC-NOS activation) for 30min at 37°C. RBC-NOS Ser¹¹⁷⁷ phosphorylation, indicating enzyme activation, was determined using immunohistochemical procedures, NO measurements were carried out via DAF fluorometry, RBC deformability was measured via ektacytometry and S-nitrosylation pattern of RBC proteins was determined using modified Biotin-switch assay.

The results showed that blood incubation with wortmannin significantly decreased RBC-NOS activation, NO-production and RBC deformability. The latter was caused by reduction of S-nitrosylation of RBC proteins. It is suggested that RBC-NOS produced NO protects free sulhydryl groups of RBC cytoskeleton from being oxidized, e.g. The absence of NO represents a loss of these protective mechanisms, thereby possibly leading to changes in the cytoskeletal structure and finally reducing RBC deformability. The present results therefore improve the understanding of RBC-NOS and NO signaling, which may benefit the treatment of microcirculatory disorders. Further studies are needed to identify the proteins which are influenced by RBC-NOS produced NO.