Alterations of circadian expressions of clock genes in Dahl salt-sensitive rats fed a high-salt diet
Alterations of circadian expressions of clock genes in Dahl salt-sensitive rats fed a high-salt diet
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DOI：
10.1161/01.hyp.0000082766.63952.49
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发表时间：
2003-08-01
期刊：
影响因子：
8.3
通讯作者：
Yokoyama, M
中科院分区：
文献类型：
--
作者：
Mohri, T;Emoto, N;Yokoyama, M
在哺乳动物中，行为和生理过程表现出24小时的节律，由中枢和外周振荡器组成的昼夜节律系统调节。由于各种心血管功能表现出昼夜变化，而血压昼夜变化的异常模式具有心血管并发症的高风险，因此我们研究了在高血压动物模型中时钟基因的表达是否发生了变化。在Dahl盐敏感大鼠喂食高盐(4%氯化钠)6周(DS-H)后，无线电遥测显示血压昼夜变化的幅度增加。DS-H组心脏/体重比、肾重/体重比均较高。超声心动图显示DS-H组左室壁厚度较大。Northern印迹分析和单余量分析表明，与正常盐饮食组相比，DS-H大鼠心脏、肝脏和肾脏中时钟基因(mPer2、BMal1和DBP)的昼夜表达变化幅度显著降低，肝脏中的BMal1除外。生物钟调控基因纤溶酶原激活物抑制物-1在DS-H心脏的昼夜表达变化减弱。目前的结果表明，DS-H表现出外周时钟基因的昼夜节律表达改变。详细分析时钟基因的昼夜节律表达与血压调节之间的关系，可能会揭示心血管疾病的时序治疗的作用。
In mammals, behavioral and physiologic processes display 24-hour rhythms that are regulated by a circadian system consisting of central and peripheral oscillators. Because various cardiovascular functions show diurnal variations and abnormal patterns of circadian blood pressure variation carry a high risk of cardiovascular complications, we investigated whether the expression of clock genes is altered in an animal model of hypertension. In Dahl salt-sensitive rats fed a high-salt (4% NaCl) diet for 6 weeks (DS-H), radiotelemetry monitoring showed increased amplitude of circadian variations in blood pressure. The ratio of heart weight to body weight and the ratio of kidney weight to body weight were higher in DS-H. Echocardiographic data showed that the wall thickness of the left ventricle was greater in DS-H. Northern blot analysis and single cosinor analysis revealed that the amplitudes of circadian expression changes of the clock genes (mPer2, Bmal1, and dbp) in the heart, liver, and kidney were significantly decreased in DS-H rats compared with a normal-salt-diet group, except for Bmal1 in the liver. The circadian expression changes of plasminogen activator inhibitor-1, a clock-regulated gene, were attenuated in the hearts of DS-H. The present results demonstrate that DS-H show altered circadian expression of peripheral clock genes. Detailed analyses of the relation between circadian expression of clock genes and blood pressure regulation might reveal a role for chronologic therapy of cardiovascular disease.