Yamamoto M, Kawanobe Y, Takahashi H, Shimazawa E, Kimura S, Ogata E
J Clin Invest. 1984 Aug;74(2):507-13. doi: 10.1172/JCI111448.
To examine the role of vitamin D in the renal tubular handling of calcium, clearance studies were performed in three groups of rats: group A rats fed a standard vitamin D-deficient diet (Ca 0.45%, P 0.3%) for 6 wk, were hypocalcemic with secondary hyperparathyroidism; group B rats fed the same diet as in group A but with high calcium (Ca 1.4%) and 20% lactose, were normocalcemic and without secondary hyperparathyroidism; group C rats fed the same diet as in group A but supplemented with 25 U of vitamin D3 orally twice a week, were normocalcemic, vitamin D-replete, and euparathyroid. After thyroparathyroidectomy (TPTX), each rat was infused intravenously with an electrolyte solution that contained a fixed concentration of calcium (0-30 mM) with or without parathyroid hormone (PTH; 0.75 or 2.5 U/h) at a rate of 3 ml/h. Urinary calcium excretion and serum calcium concentrations were measured between 16 and 19 h of the infusion, and the apparent threshold of calcium excretion was determined. The threshold of calcium excretion was lower in vitamin D-deficient TPTX rats (groups A and B) than in vitamin D-replete TPTX rats (group C), and not different between group A and group B. Administration of PTH at a dose of 0.75 U/h increased the threshold of calcium excretion by approximately 0.6 mM in group C, but did not alter the threshold either in group A or group B. Administration of a higher dose of PTH (2.5 U/h) raised the threshold similarly in both group A and group B to the extent comparable with that in group C, when it was given 0.75 U/h of PTH. These results demonstrate that the renal threshold of calcium excretion is decreased in the vitamin D-deficient rats independent of the secondary hyperparathyroidism, and that the higher dose of PTH was necessary to raise the calcium threshold in vitamin D-deficient rats. Thus, present study indicates the presence of dual effects of vitamin D on renal tubular handling of calcium; the one is to facilitate renal calcium reabsorption and the other is to enhance the responsiveness of the tubule to PTH.
为研究维生素D在肾小管钙处理中的作用,对三组大鼠进行了清除率研究:A组大鼠喂食标准的维生素D缺乏饮食(钙0.45%,磷0.3%)6周,出现低钙血症并伴有继发性甲状旁腺功能亢进;B组大鼠喂食与A组相同的饮食,但添加高钙(钙1.4%)和20%乳糖,血钙正常且无继发性甲状旁腺功能亢进;C组大鼠喂食与A组相同的饮食,但每周口服补充两次25 U维生素D3,血钙正常、维生素D充足且甲状旁腺功能正常。甲状腺甲状旁腺切除术后(TPTX),给每只大鼠静脉输注一种电解质溶液,该溶液含有固定浓度的钙(0 - 30 mM),并以3 ml/h的速率添加或不添加甲状旁腺激素(PTH;0.75或2.5 U/h)。在输注16至19小时之间测量尿钙排泄和血清钙浓度,并确定钙排泄的表观阈值。维生素D缺乏的TPTX大鼠(A组和B组)的钙排泄阈值低于维生素D充足的TPTX大鼠(C组),且A组和B组之间无差异。以0.75 U/h的剂量给予PTH可使C组的钙排泄阈值升高约0.6 mM,但对A组或B组的阈值均无影响。给予更高剂量的PTH(2.5 U/h)可使A组和B组的阈值同样升高至与给予0.75 U/h PTH时C组相当的程度。这些结果表明,维生素D缺乏的大鼠中钙排泄的肾阈值降低,与继发性甲状旁腺功能亢进无关,且在维生素D缺乏的大鼠中需要更高剂量的PTH来提高钙阈值。因此,本研究表明维生素D对肾小管钙处理存在双重作用;一是促进肾钙重吸收,另一是增强肾小管对PTH的反应性。