AJP - Renal Physiology, Vol 259, Issue 1 122-F129, Copyright © 1990 by American Physiological Society

ARTICLES

Vitamin D-induced chronic hypercalcemia inhibits thick ascending limb NaCl reabsorption in vivo

L. N. Peterson
Department of Physiology, University of Ottawa, Ontario, Canada.

Chronic hypercalcemia (HC) induced by dihydrotachysterol (DHT) is associated with a nephrogenic concentrating defect. The purpose of the present study is to assess the effects of HC on thick ascending limb (TAL) NaCl reabsorption in vivo by use of micro stop-flow technique. Feeding DHT (4.25 mg/kg diet) to rats was associated with an increase in plasma [Ca] within 24 h from 2.21 +/- 0.049 to 2.71 +/- 0.047 mM (P less than 0.001), which remained elevated during the 7-day period of study. Ambient plasma arginine vasopressin (AVP) in polydipsic HC rats was 3.10 +/- 0.605 pg/ml, a value not different from that measured in pair-fed control rats (1.82 +/- 0.260 pg/ml). A urine-concentrating defect developed after 3 days and occurred without nephrocalcinosis or reduced glomerular filtration rate (GFR). The estimated TAL [NaCl] after all stop-flow periods in HC rats did not decrease to the same extent as in controls. The rate constant of NaCl reabsorption derived from linear regression analysis of the ln[NaCl] vs. time for 0-15 s was significantly reduced by 25% in the HC nephrons. In addition, the minimum [NaCl] established after 30-60 s of contact time increased by 36% in HC nephrons. These data provide evidence that reduced TAL NaCl reabsorption, and not reduced GFR, nephrocalcinosis, or deficient AVP, contributes to the presence of a renal concentrating defect in DHT-induced chronic HC.

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