1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system
1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system
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DOI：
10.1172/jci0215219
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发表时间：
2002-07-01
影响因子：
15.9
通讯作者：
Cao, LP
中科院分区：
文献类型：
--
作者：
Li, YC;Kong, J;Cao, LP
肾素-血管紧张素系统在血压、电解质和容量稳态的调节中起核心作用，其不适当的激活可能是高血压、心脏病发作和中风的主要危险因素。来自临床研究的越来越多的证据表明，循环维生素D水平与血压和/或血浆肾素活性之间存在反比关系，但其机制尚不清楚。我们发现，在维生素D受体缺失（VDR缺失）小鼠中，肾素表达和血浆血管紧张素II的产生增加了数倍，导致高血压、心脏肥大和饮水量增加。然而，控制肾素合成的盐和体积感应机制在突变小鼠中仍然完好无损。在野生型小鼠中，抑制1，25-二羟维生素D-3 [1，25（OH）（2）D-3]的合成也导致了肾素表达的增加，而1，25（OH）（2）D-3注射导致了肾素抑制。我们发现，维生素D对肾素表达的调节不依赖于钙代谢，1，25（OH）（2）D-3通过VDR介导的机制显著抑制细胞培养中的肾素转录。因此，1，25（OH）（2）D-3是一种新的肾素-血管紧张素系统的负性内分泌调节剂。它在电解质，容量和血压稳态中的明显关键作用表明维生素D类似物可以帮助预防或改善高血压。
Inappropriate activation of the renin-angiotensin system, which plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis, may represent a major risk factor for hypertension, heart attack, and stroke. Mounting evidence from clinical studies has demonstrated an inverse relationship between circulating vitamin D levels and the blood pressure and/or plasma renin activity, but the mechanism is not understood. We show here that renin expression and plasma angiotensin II production were increased severalfold in vitamin D receptor-null (VDR-null) mice, leading to hypertension, cardiac hypertrophy, and increased water intake. However, the salt- and volume-sensing mechanisms that control renin synthesis are still intact in the mutant mice. In wild-type mice, inhibition of 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] synthesis also led to an increase in renin expression, whereas 1,25(OH)(2)D-3 injection led to renin suppression. We found that vitamin D regulation of renin expression was independent of calcium metabolism and that 1,25(OH)(2)D-3 markedly suppressed renin transcription by a VDR-mediated mechanism in cell cultures. Hence, 1,25(OH)(2)D-3 is a novel negative endocrine regulator of the renin-angiotensin system. Its apparent critical role in electrolytes, volume, and blood pressure homeostasis suggests that vitamin D analogues could help prevent or ameliorate hypertension.