Schedl H P, Miller D L, Pape J M, Horst R L, Wilson H D
J Clin Invest. 1984 Apr;73(4):980-6. doi: 10.1172/JCI111323.
Serum ionized calcium levels are lower and immunoreactive parathyroid hormone levels are higher in the spontaneously hypertensive (SH) rat than in the normotensive Wistar-Kyoto (WKy) control. We postulated that there is either a defect in the regulation of vitamin D metabolism by parathyroid hormone or that the gut target organ for vitamin D in the SH rat is unresponsive. To test these hypotheses we measured serum concentrations of vitamin D metabolites and intestinal transport of calcium and sodium. Compared with that of WKy controls, in vitro calcium transport by duodenal sacs of the SH rat was decreased (P less than 0.001) at 5 wk, before the development of hypertension, and at 12 wk, after hypertension was well established. When measured in vivo in the most proximal 20 cm of small intestine, maximum velocity (Vmax) for calcium transport was decreased (P less than 0.05) and net absorption of sodium and water was increased (P less than 0.05) in SH rats as compared with WKy rats. Vmax for calcium transport was also decreased (P less than 0.05) in the most distal 20 cm of small intestine of SH rats, but net sodium and water transport were the same in SH and WKy rats. At 12 wk, serum concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] was the same in both SH and WKy groups, but its precursor, 25-hydroxycholecalciferol, was increased (P less than 0.05) in the SH rat. We conclude that in the SH rat: (a) the concentration of 1,25-(OH)2D3 is inappropriately low in relation to the elevated immunoreactive parathyroid hormone and the depressed calcium absorption, suggesting a defect in the regulation of vitamin D metabolism; and (b) the depressed calcium absorption, in the setting of normal concentrations of [1,25-(OH)2D3], demonstrates unresponsiveness of the gut to vitamin D and may explain in part the low serum ionized calcium found in earlier studies. The presence of these abnormalities before we found a significant difference in blood pressure suggests that they may be causal, not secondary, to the hypertension.
自发性高血压（SH）大鼠的血清离子钙水平低于正常血压的Wistar-Kyoto（WKy）对照大鼠，而免疫反应性甲状旁腺激素水平则高于WKy对照大鼠。我们推测，要么是甲状旁腺激素对维生素D代谢的调节存在缺陷，要么是SH大鼠中维生素D的肠道靶器官无反应。为了验证这些假设，我们测量了维生素D代谢产物的血清浓度以及钙和钠的肠道转运。与WKy对照大鼠相比，SH大鼠十二指肠囊在5周龄（高血压发生前）和12周龄（高血压确立后）时的体外钙转运均降低（P<0.001）。在体内测量小肠最近端20厘米时，与WKy大鼠相比，SH大鼠的钙转运最大速度（Vmax）降低（P<0.05），钠和水的净吸收增加（P<0.05）。SH大鼠小肠最远端20厘米处的钙转运Vmax也降低（P<0.05），但SH大鼠和WKy大鼠的钠和水净转运相同。在12周龄时，SH组和WKy组的血清1,25-二羟胆钙化醇[1,25-(OH)2D3]浓度相同，但其前体25-羟胆钙化醇在SH大鼠中升高（P<0.05）。我们得出结论，在SH大鼠中：（a）相对于升高的免疫反应性甲状旁腺激素和降低的钙吸收，1,25-(OH)2D3的浓度过低，提示维生素D代谢调节存在缺陷；（b）在[1,25-(OH)2D3]浓度正常的情况下钙吸收降低，表明肠道对维生素D无反应，这可能部分解释了早期研究中发现的血清离子钙水平低的原因。在我们发现血压有显著差异之前就存在这些异常，表明它们可能是高血压的病因，而非继发于高血压。
