Inhibition of platelet-derived mitogen release by nitric oxide (EDRF)

Platelets exposed to thrombogenic surfaces adhere, aggregate and release mitogenic substances from their alpha-granules. Endothelium-derived relaxing factor (EDRF) which has been identified as nitric oxide (NO) has been reported to inhibit platelet aggregation. We now report that NO inhibits mitogen release from stimulated human platelets. Mitogenic activity was assayed on mouse fibroblast 3T3 cells using incorporation of 3H-thymidine. Serum from collagen-aggregated platelets significantly increased 3H-thymidine incorporation by 3T3 cells above that of serum from control platelets. Both this increase and platelet aggregation were blocked by NO and prostacyclin in a dose related manner. The inhibitory activity of NO decayed with time when incubated in platelet-free plasma at 37 degrees C, but was still detectable after 2 minutes.