INDAPAMIDE INHIBITS HUMAN PLATELET-AGGREGATION IN-VITRO - COMPARISON WITH HYDROCHLOROTHIAZIDE

Among antihypertensive drugs with diuretic properties, indapamide was shown to inhibit platelet growth factors production in diabetic hypert ensive patients, suggesting an antiplatelet activity. The present stud y aimed to demonstrate the antiaggregating properties of indapamide. T he effect of indapamide on platelet function was compared in vitro to that of hydrochlorothiazide. Indapamide (100 muM) inhibited the second wave of adenosine diphosphate-induced aggregation and inhibited colla gen-induced aggregation of platelet rich plasma by 50%. Using isolated platelets, indapamide also inhibited aggregation induced by low doses of thrombin (70% inhibition with 0.035 U/ml). This inhibition was dos e-dependent and was stili observed in presence of high thrombin concen trations, although the inhibition was moderate. Inhibitory effect of i ndapamide was more pronounced on the release reaction. Indapamide inhi bited the thrombin-induced release of serotonin from dense granules by up to 80%. Hydrochlorothiazide at the same concentrations had no effe ct on platelet aggregation, and the inhibitory effect on the secretion was inconsistent and never exceeded 30%. By contrast, when the aggreg ation inducer was arachidonic acid, indapamide had no effect either on aggregation or on thromboxane formation, indicating that it was not a cting on arachidonic catabolism. Calcium mobilization evoked by thromb in stimulation and measured with the fluorescent dye Indo 1 was also r educed in presence of indapamide by 30%. Myosin light chain and plecks trin phosphorylation induced by thrombin were also reduced. These resu lts demonstrate that indapamide inhibits platelet responses by inhibit ing calcium mobilization. The antiaggregating properties of indapamide could contribute to normalize the hyperresponsiveness of platelets fr om hypertensive patients.