Takenaka Tsuneo, Inoue Tsutomu, Ohno Yoichi, Miyazaki Takashi, Nishiyama Akira, Ishii Naohito, Suzuki Hiromichi
International University of Health and Welfare, Department of Medicine, Minato, Tokyo, Japan.
Kidney Blood Press Res. 2014;39(1):17-27. doi: 10.1159/000355773. Epub 2014 Apr 30.
BACKGROUND/AIMS: Vitamin D increases renal expression of klotho in normotensive rats. Klotho reduces oxidative stress.
In this study, we aimed to determine if vitamin D would suppress oxidative stress using 4 groups of hypertensive rats: uninephrectomized, stroke-prone, spontaneously hypertensive rats fed a high-salt (6%) diet (controls; C); those treated with irbesartan (I); those treated with calcitriol (V); and those treated with both irbesartan and calcitriol (I+V).
Systolic blood pressure was higher in the C group than in the I and I+V groups. Albuminuria was attenuated in groups I, V, and I+V. Renal angiotensin II (AngII) concentration was lower in groups I and I+V than in group C, and plasma AngII levels of groups I and V were higher and lower than those in group C, respectively. Compared with group C, renal klotho expression, 8-epi-prostaglandin F2α excretion, and acetylcholine-induced decrease in blood pressure improved in the V and I+V groups.
The data indicate that irbesartan effectively decreases blood pressure and renal AngII levels, and improves albuminuria. Our findings indicate that vitamin D enhances klotho expression, suppressing oxidative stress and albuminuria without substantial changes in renal AngII levels. These results suggest that the amelioration of endothelium function by vitamin D involves free klotho.
背景/目的:维生素D可增加正常血压大鼠肾脏中klotho的表达。Klotho可减轻氧化应激。
在本研究中,我们旨在使用4组高血压大鼠来确定维生素D是否会抑制氧化应激:单侧肾切除、易中风的自发性高血压大鼠,喂食高盐(6%)饮食(对照组;C);接受厄贝沙坦治疗的大鼠(I);接受骨化三醇治疗的大鼠(V);以及接受厄贝沙坦和骨化三醇联合治疗的大鼠(I+V)。
C组的收缩压高于I组和I+V组。I组、V组和I+V组的蛋白尿减轻。I组和I+V组的肾脏血管紧张素II(AngII)浓度低于C组,I组和V组的血浆AngII水平分别高于和低于C组。与C组相比,V组和I+V组的肾脏klotho表达、8-表-前列腺素F2α排泄以及乙酰胆碱诱导的血压下降均有所改善。
数据表明厄贝沙坦可有效降低血压和肾脏AngII水平,并改善蛋白尿。我们的研究结果表明维生素D可增强klotho表达,抑制氧化应激和蛋白尿,而肾脏AngII水平无实质性变化。这些结果表明维生素D对内皮功能的改善涉及游离的klotho。