Merke J, Lucas P A, Szabo A, Cournot-Witmer G, Mall G, Bouillon R, Drüeke T, Mann J, Ritz E
Department of Internal Medicine, University of Heidelberg, Federal Republic of Germany.
Hypertension. 1989 Mar;13(3):233-42. doi: 10.1161/01.hyp.13.3.233.
Abnormalities of calcium metabolism and of its two principal regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol), have been reported in the spontaneously hypertensive rat (SHR). Reports of abnormal calcitriol metabolism in the SHR by several groups have not provided measurements of tissue calcitriol receptors. Similarly, few data are available as to the parathyroid status of the SHR. In the present study, circulating calcitriol levels and intestinal and parathyroid gland calcitriol receptor status were determined in male SHR and in Wistar-Kyoto (WKY) rats. Parathyroid status was investigated by determination of parathyroid gland mass together with tissue micromorphometry and by quantitative histology of bone as a measure of the biological action of parathyroid hormone. Circulating calcitriol levels were reduced in the 11-week-old SHR compared with the WKY rat (165 +/- 23 vs. 194 +/- 28 pmol/l, p less than 0.01, mean +/- SD). Calcitriol-free ratio was diminished and maximal specific binding capacity for calcitriol was increased in the SHR in parathyroid tissue (172 +/- 4.9 vs. 123 +/- 6.6 fmol/mg protein, p less than 0.01) and in intestinal mucosa with no change of receptor affinity. Plasma ionized calcium (1.29 +/- 0.05 vs. 1.45 +/- 0.35 mmol/l, p less than 0.05) and phosphate (1.5 +/- 0.26 vs. 2.4 +/- 0.03 mmol/l, p less than 0.05) were significantly lower in the SHR. Parathyroid gland mass was increased in the SHR (59 +/- 12 vs. 17 +/- 7 micrograms/100 g body wt, p less than 0.001) as a result of hyperplasia and not hypertrophy. Higher osteoclast numbers were observed in SHR bone (27.6 +/- 0.79 vs. 23.9 +/- 0.66 osteoclasts/mm2, p less than 0.01), suggesting increased parathyroid hormone activity. In summary, in the 11-week-old SHR we observed reduced circulating calcitriol levels together with increased tissue calcitriol receptor numbers, increased parathyroid gland mass, and histological evidence of hyperparathyroidism. It is possible that these abnormalities influence the development of hypertension in the SHR.
自发性高血压大鼠（SHR）已被报道存在钙代谢及其两种主要调节激素——甲状旁腺激素和1,25 - 二羟维生素D3（骨化三醇）的异常。多个研究小组报道了SHR中骨化三醇代谢异常，但均未对组织骨化三醇受体进行测量。同样，关于SHR甲状旁腺状态的数据也很少。在本研究中，测定了雄性SHR和Wistar - Kyoto（WKY）大鼠的循环骨化三醇水平以及肠道和甲状旁腺的骨化三醇受体状态。通过测定甲状旁腺重量、组织显微形态学以及作为甲状旁腺激素生物学作用指标的骨定量组织学来研究甲状旁腺状态。与WKY大鼠相比，11周龄的SHR循环骨化三醇水平降低（165±23对194±28 pmol/l，p＜0.01，平均值±标准差）。SHR甲状旁腺组织（172±4.9对123±6.6 fmol/mg蛋白，p＜0.01）和肠黏膜中无受体亲和力变化，但骨化三醇游离比例降低，骨化三醇最大特异性结合能力增加。SHR的血浆离子钙（1.29±0.05对1.45±0.35 mmol/l，p＜0.05）和磷酸盐（1.5±0.26对2.4±0.03 mmol/l，p＜0.05）显著降低。由于增生而非肥大，SHR的甲状旁腺重量增加（59±12对17±7微克/100克体重，p＜0.001）。在SHR骨中观察到破骨细胞数量增加（27.6±0.79对23.9±0.66个破骨细胞/mm2，p＜0.01），提示甲状旁腺激素活性增加。总之，在11周龄的SHR中，我们观察到循环骨化三醇水平降低，同时组织骨化三醇受体数量增加、甲状旁腺重量增加以及甲状旁腺功能亢进的组织学证据。这些异常可能影响SHR高血压的发展。
