THE POTENTIATION OF ADRENALINE-INDUCED IN-VITRO PLATELET-AGGREGATION BY ADP, COLLAGEN AND SEROTONIN AND ITS INHIBITION BY NAFTOPIDIL AND DOXAZOSIN IN NORMAL HUMAN-SUBJECTS

1 Aggregation in platelet-rich plasma from normotensive men was induced by adrenaline (0.25-16 mu M), ADP (0.25-16 mu M), collagen (0.25-8 mu g ml(-1)) or serotonin (10 mu M) alone, or by previously sub-threshold concentrations of adrenaline (0.03-1 mu M) in combination with sub-threshold concentrations of serotonin (2.5 mu M), ADP (0.5 mu M) or collagen (0.125 mu g ml(-1)). The effects of the alpha(1)-adrenoceptor blockers naftopidil and doxazosin on platelet aggregation were investigated. 2 The dose-response curves for collagen and ADP were unaffected by either drug. However, naftopidil (40 mu M) inhibited serotonin-induced platelet aggregation (23.9%, 95% confidence interval (CI) 10.7 to 37.1%; P < 0.01) and caused a slight shift to the right of the adrenaline dose-response curve with a mean increase in the EC(50) value of 0.5 mu M (95% CI 0.07 to 0.93 mu M; P < 0.05). Doxazosin had no effect on serotonin or adrenaline-induced aggregation. 3 A marked potentiation of the aggregation induced by subthreshold concentrations of adrenaline resulted from the prior addition of low concentrations of ADP, collagen or serotonin. 4 These potentiated responses naftopidil and to a lesser produced by naftopidil (40 mu M) on the responses of adrenaline potentiated by ADP were 58.3% (95% CI 36.8 to 79.8%; P < 0.001), serotonin 58.9% (95% CI 40.0 to 77.8%; P < 0.001), and collagen 70.9% (95% CI 52.5 to 89.3%; P < 0.001). Those produced by doxazosin (30 mu M) were 24.6% (95% CI 3.3 to 45.9%; P < 0.05) with ADP, 28.0% (95% CI 4.1 to 51.9%; P 0.05) with serotonin, and 42.0% (95% CI 15.1 to 68.9%; P < 0.01) with collagen. 5 The incomplete inhibition of platelet aggregation caused by naftopidil and doxazosin may prove clinically advantageous with regard to their anti-thrombotic potential.