The possible mode of action of indapamide: a review.

It is not clear whether indapamide reduces blood pressure by a vasodilator or a diuretic action. This review attempts to answer this fundamental question. Cardiovascular studies show small increases in cardiac output, heart rate and stroke volume with a significant reduction in peripheral resistance. Indapamide, in vitro, directly inhibits pressor stimuli probably through a reduction of calcium flux in vascular smooth muscle, whilst diuretics are inactive. In vivo studies in man also show a reduction in sensitivity to pressor doses of noradrenaline and angiotensin without an increase in adrenergic sensitivity. However, indapamide does have mild diuretic activity at therapeutic doses, as shown by changes in plasma sodium, potassium, urea, uric acid and a reduction in body weight, but the changes are appreciably less than with thiazides. These results would suggest that indapamide has both diuretic and vasodilator properties. A low urinary excretion and specific accumulation into arterial smooth muscle of this lipophilic molecule may provide a rationale for this dual activity.