Is hydrochlorothiazide-induced hypocalciuria due to inhibition of prostaglandin E2 synthesis?
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 stoneformers 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 less than 0.001), hydrochlorothiazide also promoted a significant fall in urinary prostaglandin E2 (P less than 0.001), plasma bicyclo-prostaglandin E2 (P less than 0.001) and 1,25-dihydroxyvitamin D (P less than 0.01), and an increase in plasma parathyroid hormone (P less than 0.025), whereas plasma 25-hydroxyvitamin D was unchanged. 3. A positive correlation between urinary Ca2+ and prostaglandin E2 was present before (P less than 0.00005), but not after, hydrochlorothiazide. Plasma bicyclo-prostaglandin E2 and plasma 1,25-dihydroxyvitamin D were positively correlated both before (P less than 0.005) and after (P less than 0.005) hydrochlorothiazide, as was also the percentage change in each induced by the drug (P less than 0.05). Furthermore, the changes in plasma 25-hydroxyvitamin D and plasma 1,25-dihydroxyvitamin D after hydrochlorothiazide were negatively correlated (P less than 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 alpha-hydroxylase activity.
Caló
L
L
Institute of Internal Medicine, University of Padova, Italy.
Cantaro
S
S
Marchini
F
F
Giannini
S
S
Castrignano
R
R
Gambaro
G
G
Antonello
A
A
Baggio
B
B
D'Angelo
A
A
Williams
H
H
D000328:Adult; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000652:urine*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000652:urine; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D013997:Time Factors; D014545:Urinary Calculi / Q000517:prevention & control
D010281:Parathyroid Hormone; D006852:Hydrochlorothiazide; D002117:Calcitriol; D015232:Dinoprostone; D002118:Calcium