1. Since prostaglandin E2 could play a role in idiopathic hypercalciuria, and considering the well-established hypocalciuric action of hydrochlorothiazide, we have evaluated the effect of 15 days' treatment with hydrochlorothiazide in 10 hypercalciuric male stone-formers on urinary Ca2+ and prostaglandin E2, as well as on plasma bicyclo-prostaglandin E2, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone. 2. In addition to lowering urinary Ca2+ (P<0.001), hydrochlorothiazide also promoted a significant fall in urinary prostaglandin E2 (P<0.001), plasma bicycloprostaglandin E2 (P<0.001) and 1,25-dihydroxyvitamin D (P<0.01), and an increase in plasma parathyroid hormone (P<0.025), whereas plasma 25-hydroxyvitamin D was unchanged. 3. A positive correlation between urinary Ca2+ and prostaglandin E2 was present before (P<0.00005), but not after, hydrochlorothiazide. Plasma bicycloprostaglandin E2 and plasma 1,25-dihydroxyvitamin D were positively correlated both before (P<0.005) and after (P<0.005) hydrochlorothiazide, as was also the percentage change in each induced by the drug (P<0.05). Furthermore, the changes in plasma 25-hydroxyvitamin D and plasma 1,25-dihydroxyvitamin D after hydrochlorothiazide were negatively correlated (P<0.05). 4. It is suggested that a block of prostaglandin E2 synthesis plays a role in the effect of hydrochlorothiazide on Ca2+ metabolism, most probably through an inhibition of 1 α-hydroxylase activity.
