Effect of hydrochlorothiazide on 1,25-dihydroxyvitamin D3-induced changes in calcium metabolism in experimental...

1. Chronic administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can normalize plasma calcium in human hypoparathyroidism and in thyroparathyroidectomized animals. The effect of 1,25(OH)2D3 on plasma calcium is associated with an increase in urinary calcium excretion. In an attempt to prevent this increase thyroparathyroidectomized rats receiving 1,25(OH)2D3 were also treated with hydrochlorothiazide for 9-11 days. 2. Calcium clearance studies show that hydrochlorothiazide stimulated the tubular reabsorption of calcium in thyroparathyroidectomized rats treated with 1,25(OH)2D3. 3. Calcium balance and kinetic studies indicated that hydrochlorothiazide decreased 1,25(OH)2D3-induced hypercalciuria in thyroparathyroidectomized rats. Hydrochlorothiazide did not affect the 1,25(OH)2D3-induced increase in plasma calcium. The hypocalciuric effect of hydrochlorothiazide was not associated with significant changes in calcium deposition into or release from bone. 4. In thyroparathyroidectomized rats treated with 1,25(OH)2D3 the hypocalciuric effect of hydrochlorothiazide was associated with a fall in intestinal calcium absorption. Overall, the calcium balance was unaffected. 5. Thus it appears that hydrochlorothiazide reduces the 1,25(OH)2D3-induced hypercalciuria in parathyroid hormone-deficient animals by decreasing intestinal calcium absorption. Despite the decreased absorption, hydrochlorothiazide does not reduce the 1,25(OH)2D3-induced increase in plasma calcium.