Attenuation of Platelet-Induced Vasorelaxation by Pretreatment of Platelets with Oxidized Low Density Lipoproteins: Important Role of Serotonin

Aggregating platelets cause relaxation of precontracted vascular tissues with intact endothelium. To determine the modulation of vasorelaxation by lipoprotein-rich platelets, rat platelets were preincubated with buffer, native low density lipoprotein (n-LDL, 100 μg protein/ml), oxidized LDL (ox-LDL, 100 μg protein/ml) or high density lipoprotein (HDL, 100 μg protein/ml) at 37°C for 1 hour, washed twice, and then suspended into organ baths containing precontracted endothelium-intact rat aortic rings. While all platelet preparations caused relaxation of rat aortic rings, the magnitude of relaxation induced by ox-LDL-treated platelets was less than that by buffer-treated platelets (p < 0.05). Pretreatment of platelets with native LDL or HDL did not affect the magnitude of vasorelaxation. Treatment of platelets with the cyclooxygenase inhibitor indomethacin (5 × 10−5 M) did not affect the attenuated vasorelaxation in response to ox-LDL-treated platelets. Pretreatment of aortic rings with the thromboxane (TX) A2/endoperoxide receptor antagonist SQ29,548 (5 × 10−6 M) also had no effect on the attenuated relaxation. However, pretreatment of aortic rings with the serotonin2 receptor antagonist LY53,857 (5 × 10−5 M) totally reversed the attenuated vasorelaxation. Ox-LDL-treated platelets were also found to exhibit greater thrombin-induced aggregation and 14C-serotonin release (p < 0.05 vs. buffer treated platelets). These observations indicate that rat aortic rings exhibit diminished relaxation when exposed to ox-LDL-treated platelets, and this effect is mediated primarily via enhanced serotonin release from ox-LDL-treated platelets.