Popovtzer M M, Robinette J B, DeLuca H F, Holick M F
J Clin Invest. 1974 Mar;53(3):913-21. doi: 10.1172/JCI107632.
The acute effect of i.v. and direct intrarenal arterial infusion of 25-hydroxycholecalciferol (25HCC) and 1,25-dihydroxycholecalciferol (1,25-DHCC) on renal handling of phosphorus was evaluated in the following groups of rats: (a) intact animals, (b) parathyroidectomized (PTX) hypocalcemic rats, (c) PTX rats in which normocalcemia was maintained with calcium supplements and (d) PTX animals in which urinary phosphorus was augmented by (i) i.v. sodium phosphate, (ii) expansion of the extracellular fluid volume with normal saline, and (iii) i.v. parathyroid hormone (PTH). Clearances of inulin (C(In)), phosphorus (C(P)), and fractional clearances of phosphorus (C(P)/C(In)) of the experimental groups were compared with those of the corresponding control groups, and the clearances of the infused kidneys with those of the contralateral kidneys. In intact animals, i.v. 25HCC decreased C(P)/C(In) from 0.29+/-0.04 (mean +/-SE) to 0.19+/-0.04, and i.v. 1,25-DHCC decreased C(P)/C(In) from 0.25+/-0.04 to 0.15+/-0.02. The intrarenal infusion of both 25HCC and 1,25DHCC into intact animals failed to produce a unilateral change; however, it decreased C(P)/C(In) bilaterally. i.v. and intrarenal infusions of 25HCC or 1,25DHCC in PTX hypocalcemic and normocalcemic rats, and i.v. infusions of 25HCC in PTX rats receiving either sodium phosphate or normal saline, all failed to produce significant changes in C(P)/C(In). In contrast, 24HCC given i.v. to PTX animals receiving exogenous PTH was associated with a significant fall in C(P)/C(In), from 0.34+/-0.08 to 0.13+/-0.02. These results indicate that 25HCC enhances tubular reabsorption of phosphorus in rats, only in the presence of either endogenous or exogenous circulating PTH, but not in its absence and thus imply a PTH-dependent mechanism of 25HCC action on the kidney. This effect does not appear to be related to the conversion of 25HCC into 1,25DHCC, since the latter fails to affect tubular reabsorption of phosphorus in PTX rats.
通过静脉注射和直接肾内动脉注射25 - 羟基胆钙化醇(25HCC)和1,25 - 二羟基胆钙化醇(1,25 - DHCC),对下列几组大鼠肾脏处理磷的急性效应进行了评估:(a)完整动物;(b)甲状旁腺切除(PTX)的低钙血症大鼠;(c)通过补充钙维持血钙正常的PTX大鼠;以及(d)通过以下方式使尿磷增加的PTX动物:(i)静脉注射磷酸钠;(ii)用生理盐水扩充细胞外液量;(iii)静脉注射甲状旁腺激素(PTH)。将实验组的菊粉清除率(C(In))、磷清除率(C(P))以及磷的分数清除率(C(P)/C(In))与相应对照组进行比较,并将注入侧肾脏的清除率与对侧肾脏的清除率进行比较。在完整动物中,静脉注射25HCC使C(P)/C(In)从0.29±0.04(平均值±标准误)降至0.19±0.04,静脉注射1,25 - DHCC使C(P)/C(In)从0.25±0.04降至0.15±0.02。向完整动物肾内注射25HCC和1,25 - DHCC均未产生单侧变化;然而,双侧均降低了C(P)/C(In)。在PTX低钙血症和血钙正常的大鼠中静脉注射和肾内注射25HCC或1,25 - DHCC,以及在接受磷酸钠或生理盐水的PTX大鼠中静脉注射25HCC,均未使C(P)/C(In)产生显著变化。相比之下,给接受外源性PTH的PTX动物静脉注射24HCC会使C(P)/C(In)显著下降,从0.34±0.08降至0.13±0.02。这些结果表明,25HCC仅在存在内源性或外源性循环PTH时增强大鼠肾小管对磷的重吸收,在其不存在时则不然,因此意味着25HCC对肾脏的作用机制依赖于PTH。这种效应似乎与25HCC转化为1,25 - DHCC无关,因为后者未能影响PTX大鼠肾小管对磷的重吸收。