Oxidized LDL Decreases l -Arginine Uptake and Nitric Oxide Synthase Protein Expression in Human Platelets

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Abstract
Background Oxidized LDL (ox-LDL) promotes vasoconstriction and platelet activation. The present study was undertaken to determine the involvement of the l-arginine–nitric oxide (NO) pathway in ox-LDL–mediated platelet activation. Methods and Results Washed human platelets were incubated with native LDL or ox-LDL for 1 hour at 37°C followed by measurement of platelet function and indexes of the l-arginine–NO pathway. Ox-LDL but not native LDL caused a concentration-dependent increase in thrombin-induced platelet aggregation and 14C-serotonin release. These effects of ox-LDL were inhibited by pretreatment of platelets with l-arginine, the precursor of NO. Ox-LDL also caused a concentration-dependent reduction in the uptake of 3H-l-arginine by platelets. In addition, NO synthase activity, measured as conversion of 3H-l-arginine to 3H-l-citrulline, decreased on incubation of platelet cytosol with ox-LDL. Nitrite production was also reduced by treatment of platelets with ox-LDL. These effects of ox-LDL on NO s...