F. Rendu et al., INDAPAMIDE INHIBITS HUMAN PLATELET-AGGREGATION IN-VITRO - COMPARISON WITH HYDROCHLOROTHIAZIDE, Journal of cardiovascular pharmacology, 22, 1993, pp. 190000057-190000063
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.