自发性高血压大鼠中骨化三醇的代谢降解与合成

Metabolic degradation and synthesis of calcitriol in spontaneously hypertensive rat.

作者信息

Young E W, Hsu C H, Patel S, Simpson R U, Komanicky P

出版信息

Am J Physiol. 1987 Jun;252(6 Pt 1):E778-82. doi: 10.1152/ajpendo.1987.252.6.E778.

DOI:10.1152/ajpendo.1987.252.6.E778

PMID:3591939

Abstract

Plasma calcitriol concentration is unexpectedly low in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY) in view of previous findings of low plasma ionized calcium, hypophosphatemia, and hyperparathyroidism in SHR. Also, parathyroid hormone (PTH) and other exogenous stimuli cause a smaller increment in plasma calcitriol in SHR than in WKY. We investigated whether these differences in plasma calcitriol levels were due to decreased production rate (PR) or increased metabolic clearance rate (MCR) in SHR using the continuous infusion-isotope equilibration technique. In the basal state, MCR was 0.306 +/- 0.048 ml X min-1 X kg-1 in SHR and 0.284 +/- 0.026 ml X min-1 X kg-1 in WKY (P = NS). Estimated PR was lower in SHR (22.7 vs. 33.7 ng X day-1 X kg-1). With PTH infusion (3 U X h-1 X 100 g-1 for 20 h), MCR was 0.220 +/- 0.011 ml X min-1 X kg-1 in SHR and 0.256 +/- 0.017 ml X min-1 X kg-1 in WKY (P = NS). Measured PR was markedly lower in SHR (154 +/- 24 vs. 262 +/- 27 ng X day-1 X kg-1; P less than 0.02). Basal plasma PTH, total plasma calcium, and plasma inorganic phosphate were not different between SHR and WKY. Thus, SHR show diminished calcitriol production under basal condition and with PTH stimulation. MCR is not increased in SHR and does not appear to be influenced by PTH or the accompanying elevation in plasma calcium and calcitriol.

摘要

鉴于之前在自发性高血压大鼠（SHR）中发现的低血浆离子钙、低磷血症和甲状旁腺功能亢进，与正常血压的Wistar-Kyoto大鼠（WKY）相比，SHR的血浆骨化三醇浓度意外地低。此外，甲状旁腺激素（PTH）和其他外源性刺激在SHR中引起的血浆骨化三醇增量比在WKY中更小。我们使用连续输注-同位素平衡技术研究了SHR中血浆骨化三醇水平的这些差异是由于生成率（PR）降低还是代谢清除率（MCR）增加所致。在基础状态下，SHR的MCR为0.306±0.048 ml·min⁻¹·kg⁻¹，WKY为0.284±0.026 ml·min⁻¹·kg⁻¹（P=无显著性差异）。SHR的估计PR较低（22.7对33.7 ng·天⁻¹·kg⁻¹）。输注PTH（3 U·h⁻¹·100 g⁻¹，持续20小时）后，SHR的MCR为0.220±0.011 ml·min⁻¹·kg⁻¹，WKY为0.256±0.017 ml·min⁻¹·kg⁻¹（P=无显著性差异）。SHR中测得的PR明显较低（154±24对262±27 ng·天⁻¹·kg⁻¹；P<0.02）。SHR和WKY之间的基础血浆PTH、总血浆钙和血浆无机磷没有差异。因此，SHR在基础条件下和PTH刺激下骨化三醇生成减少。SHR的MCR没有增加，似乎不受PTH或伴随的血浆钙和骨化三醇升高的影响。