Hydrogen peroxide at low concentrations strongly enhances the inhibitory effect of nitric oxide on platelets

Simultaneous application of NO and H2O2 to human platelets at physiologically relevant concentrations increased inhibition of platelet aggregation by NO almost 100-fold. If NO and H2O2 were mixed before the addition to platelets, the inhibitory effect remained but still depended on the presence of NO. This suggested an enhanced sensitivity of the platelets to residual NO in the presence of H2O2. The inhibition by the NO/H2O2 mixture was not due to peroxynitrite and was only partly reversed by radical scavengers. The mechanism includes enhanced formation of cyclic GMP in response to NO in the presence of H2O2. H2O2 may play a positive physiological role by amplification and/or prolongation of the action of NO.