INTERACTION OF HUMAN PLATELETS AND LEUKOCYTES IN MODULATION OF VASCULAR TONE

We tested the hypothesis that the vasodilator response to human platel ets is modulated by polymorphonuclear leukocytes (PMNs). Responses to platelets activated with thrombin, as well as PMNs activated with N-fo rmylmethionyl-leucyl-phenylalanine (FMLP), were examined in perfused r abbit carotid arteries in vitro. Activation of platelets produced mark ed dilatation, and activation of PMNs produced modest constriction in arteries preconstricted with phenylephrine. Vasodilator responses to p latelets were greatly impaired during infusion of activated PMNs. Pret reatment of PMNs with superoxide dismutase (SOD) partially restored di lator responses to platelets. Because SOD only partially restored vaso dilator responses to platelets, we tested the possibility that adenosi nediphosphatase (ADPase) activity of PMNs may degrade ADP released by platelets and thus reduce vasodilator responses. After incubation with PMNs, dilator responses to ADP, but not acetylcholine, were significa ntly impaired. These findings indicate that vasodilatation produced by activated human platelets is profoundly impaired by activated leukocy tes. We conclude that two mechanisms may account for this effect: 1) e ndothelium-derived relaxing factor, released in response to platelet-d erived ADP, is inactivated by superoxide anion generated by activated PMNs and 2) ADP is degraded by ADPase activity of PMNs, We speculate t hat platelet-leukocyte interaction may have important effects on vasom otor tone.