Vitamin D-induced chronic hypercalcemia inhibits thick ascending limb NaCl reabsorption in vivo.
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.
Peterson
L N
LN
Department of Physiology, University of Ottawa, Ontario, Canada.
D000042:Absorption; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D001784:Blood Gas Analysis; D002118:Calcium / Q000097:blood; D002245:Carbon Dioxide / Q000032:analysis; D002908:Chronic Disease; D003401:Creatine / Q000097:blood; D004327:Drinking Behavior / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006400:Hematocrit; D006863:Hydrogen-Ion Concentration; D006934:Hypercalcemia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D007671:Kidney Concentrating Ability / Q000187:drug effects / Q000502:physiology; D007684:Kidney Tubules / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000378:metabolism / Q000493:pharmacokinetics*; D013997:Time Factors; D014807:Vitamin D / Q000494:pharmacology*
D001127:Arginine Vasopressin; D014807:Vitamin D; D002245:Carbon Dioxide; D012965:Sodium Chloride; D003401:Creatine; D002118:Calcium