ENDOTHELIUM-DERIVED RELAXING FACTOR INHIBITS SHEAR STRESS-INDUCED PLATELET-AGGREGATION

The effect of endothelium-derived relaxing factor (EDRF) and related c ompounds on platelet aggregation in response to physiological and path ological levels of arterial wall shear stress (30-120 dyne/cm2) was in vestigated. Platelets in plasma, or washed platelets, aggregated marke dly in response to shear stresses generated by a cone-plate viscometer . Pre-treatment of platelets with the S-nitrosothiol compounds S-nitro so-N-acetylcysteine or S-nitrosocysteine, or with nitric oxide (NO) or SIN-1 (which is non-enzymatically metabolized to NO), resulted in dec reased platelet aggregation in response to shear stress. Non-hydrolyza ble analogues of cyclic guanosine 3',5'-monophosphate (cGMP) also inhi bited shear stress-induced platelet aggregation, and specific pharmaco logical manipulations of NO and cGMP (with methylene blue or the cGMP phosphodiesterase inhibitor M&B 22 984) resulted in alterations of int raplatelet levels of cGMP that correlated with the degree of inhibitio n of shear stress-induced platelet aggregation. These results demonstr ate that EDRF and related compounds inhibit platelet aggregation that is initiated by shear stress, and suggest that this physiologically re levant mechanism of platelet aggregation may be regulated by intraplat elet cGMP.