Alon U, Wellons M D, Chan J C
Pediatr Res. 1983 Feb;17(2):117-9. doi: 10.1203/00006450-198302000-00007.
To test the effects of chlorothiazide on vitamin-D2-induced hypercalciuria, we carried out 17 metabolic studies lasting 12 days each in adult Sprague-Dawley male rats. Three groups were studied: (A) control rats receiving only the vitamin-D2 vehicle; (B) vitamin-D2-treated rats receiving 50 IU/day; and (C) rats treated in the same manner as group B with the addition of chlorothiazide 20 mg/day for the last 6 days of the study. Urine was collected during the last 3 days, and a blood sample was obtained at the end of each study period. Analysis of the data showed that there were no significant differences between the groups in changes of serum calcium concentration (A, 6.1 +/- 0.1 mg/dl; B, 6.1 +/- 0.2 mg/dl; C, 6.0 +/- 0.2 mg/dl), serum creatinine concentration (A, 0.5 +/- 0.07 mg/dl; B, 0.52 +/- 0.08 mg/dl; C, 0.48 +/- 0.04 mg/dl), and creatinine clearance (A, 4.8 +/- 0.7 ml/min/kg; B, 5.2 +/- 1.2 ml/min/kg; C, 4.9 +/- 0.5 ml/min/kg). The administration of vitamin-D2 significantly increased the urinary calcium excretion from 6.7 +/- 1.0 mg/kg/day to 19.5 +/- 9.7 mg/kg/day (p less than 0.02), but the calciuria was inhibited in group C rats by the addition of chlorothiazide, which restored urinary calcium excretion to 6.8 +/- 2.5 mg/kg/day (p less than 0.02). Evaluation of the ratio of calcium/creatinine excretion (A, 0.19 +/- 0.03; B, 0.53 +/- 0.25; C, 0.20 +/- 0.07) and calcium/sodium excretion (A, 0.22 +/- 0.05; B, 0.48 +/- 0.25; C, 0.19 +/- 0.04) further confirmed these effects of vitamin-D2 and chlorothiazide on urine calcium excretion. We conclude that in rats conventional doses of vitamin-D2 consistently induce marked hypercalciuria, even without hypercalcemia, and that this hypercalciuria can be effectively prevented by chlorothiazide.
为了测试氯噻嗪对维生素D2诱导的高钙尿症的影响，我们对成年斯普拉格-道利雄性大鼠进行了17项代谢研究，每项研究持续12天。研究了三组：(A)仅接受维生素D2赋形剂的对照大鼠；(B)接受50 IU/天维生素D2治疗的大鼠；(C)在研究的最后6天，以与B组相同的方式治疗，但添加20 mg/天氯噻嗪的大鼠。在最后3天收集尿液，并在每个研究期结束时采集血样。数据分析表明，各组之间血清钙浓度变化（A组，6.1±0.1 mg/dl；B组，6.1±0.2 mg/dl；C组，6.0±0.2 mg/dl）、血清肌酐浓度变化（A组，0.5±0.07 mg/dl；B组，0.52±0.08 mg/dl；C组，0.48±0.04 mg/dl）和肌酐清除率变化（A组，4.8±0.7 ml/min/kg；B组，5.2±1.2 ml/min/kg；C组，4.9±0.5 ml/min/kg）均无显著差异。维生素D2的给药显著增加了尿钙排泄量，从6.7±1.0 mg/kg/天增加到19.5±9.7 mg/kg/天（p<0.02），但在C组大鼠中，添加氯噻嗪抑制了高钙尿症，使尿钙排泄量恢复到6.8±2.5 mg/kg/天（p<0.02）。对钙/肌酐排泄率（A组，0.19±0.03；B组，0.53±0.25；C组，0.20±0.07）和钙/钠排泄率（A组，0.22±0.05；B组，0.48±0.25；C组，0.19±0.04）的评估进一步证实了维生素D2和氯噻嗪对尿钙排泄的这些影响。我们得出结论，在大鼠中，常规剂量的维生素D2即使在没有高钙血症的情况下也会持续诱导明显的高钙尿症，而这种高钙尿症可以被氯噻嗪有效预防。
