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Cell-free and erythrocytic S-nitrosohemoglobin inhibits human platelet aggregation
J R Pawloski1, R V Swaminathan, J S Stamler
1Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Background:
Nitric oxide (NO) and related molecules are thought to inhibit human platelet aggregation by raising levels of cGMP.
Methods And Results:
Both oxidative stress (reactive oxygen species) and hemoglobin (Hb) seem to oppose NO effects. A major fraction of NO in the blood is bound to thiols of Hb, forming S-nitrosohemoglobin (SNO-Hb), which releases the NO group on deoxygenation in the microcirculation. Here we show that (1) both cell-free and intraerythrocytic SNO-Hb (SNO-RBC) inhibit platelet aggregation, (2) the oxidation state of the hemes in Hb influences the response--SNO-metHb (which is functionally similar to SNO-deoxyHb) has greater platelet inhibitory effects than SNO-oxyHb, and (3) the mechanism of platelet inhibition by SNO-Hb is cGMP independent.
Conclusions:
We suggest that the RBC has evolved a means to counteract platelet activation in small vessels and the proaggregatory effects of oxidative stress by forming SNO-Hb.