Indapamide inhibits human platelet aggregation in vitro: comparison with hydrochlorothiazide

Area of Science:

• Pharmacology
• Cardiovascular Research
• Hematology

Background:

• Antihypertensive drugs with diuretic properties may possess antiplatelet effects.
• Indapamide has been suggested to inhibit platelet growth factors in diabetic hypertensive patients.
• Platelet hyperresponsiveness is observed in hypertensive individuals.

Purpose of the Study:

• To demonstrate the anti-aggregating properties of indapamide.
• To compare the antiplatelet effects of indapamide with hydrochlorothiazide in vitro.
• To elucidate the mechanism underlying indapamide's effect on platelet function.

Main Methods:

• In vitro assessment of indapamide and hydrochlorothiazide on platelet-rich plasma and isolated platelets.
• Evaluation of aggregation induced by adenosine diphosphate, collagen, thrombin, and arachidonic acid.
• Measurement of serotonin release, calcium mobilization (using Indo 1), and protein phosphorylation.

Main Results:

• Indapamide significantly inhibited adenosine diphosphate- and collagen-induced platelet aggregation.
• Indapamide markedly reduced thrombin-induced serotonin release and aggregation, but not arachidonic acid-induced responses.
• Hydrochlorothiazide showed minimal effects on platelet aggregation and secretion compared to indapamide.
• Indapamide decreased thrombin-induced calcium mobilization and myosin light chain/pleckstrin phosphorylation.

Conclusions:

• Indapamide possesses significant anti-aggregating and anti-secretory properties.
• The antiplatelet mechanism of indapamide involves the inhibition of calcium mobilization.
• These findings suggest indapamide's potential to mitigate platelet hyperresponsiveness in hypertensive patients.