Effect of ANG II type I receptor antagonist and ACE inhibitor on vitamin D receptor-null mice
Effect of ANG II type I receptor antagonist and ACE inhibitor on vitamin D receptor-null mice
复制标题
DOI：
10.1152/ajpregu.00517.2002
复制
发表时间：
2003-07-01
影响因子：
2.8
通讯作者：
Li, YC
中科院分区：
文献类型：
--
作者：
Kong, J;Li, YC
我们最近发现，维生素D受体（VDR）失活的结果在失调的刺激，肾素-血管紧张素系统（RAS）。为了进一步阐明RAS激活与电解质和容量稳态异常之间的关系，我们研究了血管紧张素II I型受体拮抗剂氯沙坦和血管紧张素转换酶抑制剂卡托普利对VDR缺失小鼠的影响。氯沙坦或卡托普利治疗使VDR缺失小鼠的水摄入量和尿排泄量正常化。然而，VDR基因敲除小鼠的盐排泄增加不受任何药物的影响，表明这种异常与RAS无关。北方印迹和免疫组化分析表明，这两种药物引起了激烈的刺激，在野生型和VDR基因敲除小鼠的肾素表达，但肾素的表达仍然远远高于在治疗的VDR基因敲除小鼠比在治疗的野生型小鼠，这表明血管紧张素II反馈机制在突变小鼠保持完整。这些数据牢固地建立了RAS过度刺激和VDR缺失小鼠的异常体积稳态之间的因果关系，并证明了维生素D对肾素表达的抑制独立于体内ANG II反馈调节。
We recently showed that vitamin D receptor (VDR) inactivation results in deregulated stimulation of the renin-angiotensin system (RAS). To address further the relation between RAS activation and the abnormalities in electrolyte and volume homeostasis, we studied the effect of the ANG II type I receptor antagonist losartan and the angiotensin-converting enzyme inhibitor captopril on VDR-null mice. Treatment with losartan or captopril normalized the water intake and urine excretion of VDR-null mice. However, the increase in salt excretion in VDR-null mice was not affected by either drug, suggesting that this abnormality is independent of the RAS. Northern blot and immunohistochemical analyses revealed that both drugs caused a drastic stimulation of renin expression in wild-type and VDR-null mice, but renin expression remained much higher in the treated VDR-null mice than in the treated wild-type mice, suggesting that the ANG II feedback mechanism remains intact in the mutant mice. These data firmly established a causative relation between RAS overstimulation and the abnormal volume homeostasis in VDR-null mice and demonstrated that vitamin D repression of renin expression is independent of the ANG II feedback regulation in vivo.