Herichová Iveta, Mravec Boris, Stebelová Katarína, Krizanová Ol'ga, Jurkovicová Dana, Kvetnanský Richard, Zeman Michal
Department of Animal Physiology and Ethology, Comenius University Bratislava, Mlynská dolina B2, 842 15, Bratislava, Slovak Republic.
Mol Cell Biochem. 2007 Feb;296(1-2):25-34. doi: 10.1007/s11010-006-9294-4. Epub 2006 Aug 15.
Hypertensive TGR(mREN-2)27 rats exerting inverted blood pressure (BP) profile were used to study clock gene expression in structures responsible for BP control. TGR and control Sprague Dawley male rats were synchronized to the light:dark cycle 12:12 with food and water ad libitum. Daily rhythm in per2, bmal1, clock and dbp expression in the suprachiasmatic nucleus (SCN), rostral ventrolateral medulla (RVLM), nucleus of the solitary tract (NTS), heart and kidney was determined in both groups. Sampling occurred in regular 4 h intervals when rats of both strains were 11-weeks-old. Blood pressure and relative heart weight were significantly elevated in TGR rats in comparison with control. Expression of bmal1 and clock was up regulated in SCN of TGR rats but daily rhythm in per2 and dbp expression was similar in both groups. Mesor of per2 expression in RVLM was significantly higher in TGR than in control rats. In NTS of TGR rats expression of per2 was phase delayed by 3.5 h in comparison with control and bmal1 did not exert rhythmic pattern. Our study provided the first evidence about modified function of central and peripheral circadian oscillators in TGR rats at the level of clock gene expression. Expression of clock genes exerted up regulation in SCN and RVLM and down regulation in NTS. Circadian oscillators in selected brain structures were influenced more than oscillators in the heart and kidney by additional renin gene. Interactions of RAS and circadian system probably contribute to the development of inverted BP profile in TGR rats.
利用血压（BP）曲线倒置的高血压TGR（mREN-2）27大鼠，研究负责血压控制的结构中的生物钟基因表达。将TGR大鼠和对照Sprague Dawley雄性大鼠同步到12:12的明暗周期，自由饮食饮水。测定两组大鼠视交叉上核（SCN）、延髓头端腹外侧区（RVLM）、孤束核（NTS）、心脏和肾脏中per2、bmal1、clock和dbp表达的日节律。当两种品系的大鼠11周龄时，每隔4小时定期取样。与对照相比，TGR大鼠的血压和相对心脏重量显著升高。TGR大鼠SCN中bmal1和clock的表达上调，但两组中per2和dbp表达的日节律相似。TGR大鼠RVLM中per2表达的中值显著高于对照大鼠。与对照相比，TGR大鼠NTS中per2的表达相位延迟3.5小时，且bmal1没有呈现节律模式。我们的研究首次提供了关于TGR大鼠中枢和外周昼夜节律振荡器在生物钟基因表达水平上功能改变的证据。生物钟基因的表达在SCN和RVLM中上调，在NTS中下调。额外的肾素基因对选定脑结构中的昼夜节律振荡器的影响大于对心脏和肾脏中振荡器的影响。肾素-血管紧张素系统（RAS）与昼夜节律系统的相互作用可能有助于TGR大鼠倒置血压曲线的形成。
