Influence of naftidrofuryl, a serotonergic antagonist, on erythrocyte aggregation

Erythrocyte aggregation is an important determinant of the rheological behavior of blood and may play a critical role in nutritive tissue perfusion at the level of the microcirculation, particularly in situations of low flow. Thus, abnormal red blood cell aggregation may contribute to the pathophysiology of a variety of vascular diseases with associated microcirculatory disturbances. The action of serotonergic antagonists has a hemorheological component, although red blood cell aggregation specifically has not been addressed previously. Therefore, the effect of naftidrofuryl, a 5-hydroxytryptamine-2 receptor antagonist (5-HT₂), on erythrocyte aggregation was studied in whole blood obtained from adult human volunteers. Red blood cell aggregation was measured using a Myrenne aggregometer the operation of which is based on nephelometric principles. The results demonstrate that red blood cell aggregation is significantly reduced in comparison to controls on incubation of whole blood in the presence of naftidrofuryl. This inhibitory effect is concentration dependent and reaches a maximum (approximately 30%) between 1 and 10 μM naftidrofuryl. Furthermore, naftidrofuryl (5 μM) also inhibits red blood cell aggregation in the presence of exogenously added serotonin (1 μM) on average by approximately 18%. Significant inhibition of red blood cell aggregation could not be observed in similar experiments using whole blood suspensions essentially devoid of platelets, suggesting that these blood cellular elements are involved in mediating the effects of naftidrofuryl.