Effect of in vitro incorporation of prostanoid precursors, superoxide radical and hydrogen peroxide on platelet function.

The level of cyclic adenosine monophosphate (cAMP) in human platelets is known to be an important regulator of platelet function. The polyunsaturated fatty acids (PUFA) dihomo-gamma-linolenic acid (DHLA), and eicosapentaenoic acid (EPA), precursors of the prostaglandin (PG) 1 and 3 series respectively, were studied for their ability to stimulate platelet cAMP and/or PGE1 levels, and to inhibit platelet aggregation (PAg). Incubation of washed platelets (1 x 10(8)/ml) with 125 microM DHLA increased intraplatelet levels of PGE1 from 197 +/- 7 to 1622 +/- 9.7 picograms/10(8), cAMP from 3 +/- 0.8 to 31 +/- 1.9 picomoles/10(8), and inhibited collagen-induced PAg. Addition of 1 mumole of xanthine per unit of xanthine oxidase (a superoxide radical generating system) to the incubating medium potentiated the effects of both fatty acids, whereas 240 microM Hydrogen Peroxide (H2O2) inhibited these effects. These results suggest that: (1) DHLA may be more effective in inhibiting PAg than EPA, which has been reported to reduce the incidence of coronary diseases in some human populations; (2) That superoxide radical may activate the platelet cyclooxygenase system to increase lipid peroxidation of these PUFA prostanoid precursors and may result in the inhibition of PAg, whereas H2O2 may have an opposite effect.