EFFECTS OF RAISED EXTRACELLULAR MAGNESIUM ON PLATELET REACTIVITY

The inhibitory effects on platelet reactivity of increased extracellul ar magnesium were investigated, Wherever possible, experiments were pe rformed in hirudinized whole blood. Concentration dependent inhibition of platelet aggregation and dense granule release were observed with MgSO4. Antiaggregatory effects were identical with MgCl2, indicating t hat the effects are due to the Mg2+ ion, Antiaggregatory effects of Ca Cl2 differed from those of MgCl2, indicating that this is not a non-sp ecific divalent cation effect, MgSO4 also caused concentration-depende nt inhibition of platelet thromboxane production, Experiments in the p resence of apyrase and indomethacin showed that complex formation with ADP and inhibition of cyclo-oxygenase do not entirely account for the inhibitory effect of magnesium on platelet activation, Studies with a n anti-GPIIb/IIIa antibody showed that the inhibitory effects on the r elease reaction and thromboxane synthesis are independent of those on aggregation. The results are consistent with magnesium modifying an in tracellular signal transduction pathway common to several agonists, ra ther than the effects of magnesium being specific for one agonist, Thi s study also shows that MgSO4 inhibits agonist-induced increases in in tracellular free calcium, Increasing the extracellular concentration o f magnesium up to 10 mM had no effect on agonist-induced increments in intraplatelet free Mg2+ concentration.