AJP - Gastrointestinal and Liver Physiology, Vol 242, Issue 6 575-G581, Copyright © 1982 by American Physiological Society
Effects of chlorothiazide on 1,25-dihydroxyvitamin D3, parathyroid hormone, and intestinal calcium absorption in the rat
M. J. Favus, F. L. Coe, S. C. Kathpalia, A. Porat, P. K. Sen and L. M. Sherwood
Previous studies have shown that thiazide diuretic agents reverse secondary
hyperparathyroidism and reduce circulating 1,25-dihydroxyvitamin D3
[1,25(OH)2D3] and intestinal calcium absorption rates in patients with
idiopathic hypercalciuria of the renal-leak variety. We have investigated
whether thiazides can reverse the secondary increase in serum parathyroid
hormone (PTH) and 1,25(OH)2D3 levels or intestinal calcium absorption
induced by feeding rats a diet low in calcium (LCD, 0.02% calcium) but
adequate in phosphorus and vitamin D. We found that LCD increased
circulating immunoreactive PTH [chow vs. LCD, 0.52 +/- 0.06 vs. 1.06 +2-
0.1 (SE) ng/ml, P less than 0.001], 1,25(OH)2D3 (chow vs. LCD, 101 +/- 15
vs. 325 +/- 38 pg/ml, P less than 0.001), calcium uptake by everted gut
sacs from duodenum, ileum, and descending colon, and net calcium absorption
by descending colon studied in Ussing chambers in vitro. Chlorothiazide
(CTZ) prevented the increase in PTH during LCD (chow + CTZ vs. LCD + CTZ,
0.69 +/- 0.07 vs. 0.73 +/- 0.06, NS) but not the increase in 1,25(OH)2D3
(chow + CTZ vs. LCD + CTZ, 88 +/- 10 vs. 277 +/- 31, P less than 0.002) or
intestinal calcium transport. The drug caused no change in serum
1,25(OH)2D3 or intestinal calcium absorption in rats fed normal chow. In
rats given exogenous 1,25(OH)2D3 to stimulate intestinal calcium
absorption, CTZ reduced urine calcium excretion greatly but did not alter
intestinal calcium absorption.
