Regulation of platelet proaggregant activity in cyclooxygenase inhibition in patients with nephrolithiasis

Abstract

Aim of the study was to establish the possibility of synergism between the TP receptor for TxA2 and purinergic P2 receptors during COX inhibition, and the effect of the resulting remodeling of signaling pathways on aggregometry parameters in patients with nephrolithiasis (NLT). Materials and Methods. The study was prospective and included 30 patients with imaging evidence of urinary tract calculi who were treated with high doses of non-selective NSAIDs for analgesia. The severity of hematuria was assessed at the time of hospitalization and during 7 days of lithokinetic therapy (LKT). Analysis of functional activity of TR-receptors, purine P2X1and P2Yreceptors of platelets (Tc) was performed by turbidimetric method on ChronoLog analyzer (USA). Agonists (ATP, ADP and Arachidonic acid) were used at concentrations of EC50 and EC10. Statistical analysis was performed using MedCalc package. Results. Two waves of COX activity decrease were revealed 24h and 72h after the beginning of NSAID administration. On the 5th day of LKT, the compensatory reaction of Tc was switched on, which was reproduced at restoration of normoreactivity of TR-receptor. Purine P2X1 – and P2Y-receptor synergism had a more pronounced inducing effect on aggregation parameters compared with the interaction between P2Y-receptor and TR-receptor or TR-receptor and P2X -receptor. On the 7th day, the residual level of COX activity was reached and hyporeactivity of TR-receptor was registered; at the same time the preserved level of TxA2 synthesis did not provide limitation of hematuria. Conclusion. Upon COX inhibition, potentiation of Tc proaggregant activity is reproduced by purine P2-receptor and TR-receptor interaction due to an increase in the rate of intracellular signalling (Slope) and the number of aggregates formed (AUC).