Dept. of Medicine/Division of Physiology, Univ. of Fribourg, Chemin du Musée 5, CH-1700 Fribourg/Switzerland.
Am J Physiol Regul Integr Comp Physiol. 2010 Mar;298(3):R627-34. doi: 10.1152/ajpregu.00404.2009. Epub 2010 Jan 6.
Alterations in the circadian blood pressure pattern are frequently observed in hypertension and lead to increased cardiovascular morbidity. However, there are no studies that have investigated a possible implication of the Period2 gene, a key component of the molecular circadian clock, on the circadian rhythms of blood pressure and heart rate. To address this question, we monitored blood pressure, heart rate, and locomotor activity 24 h a day by telemetry in mice carrying a mutation in the Period2 gene and in wild-type control mice. Under a standard 12:12-h light-dark cycle, mutant mice showed a mild cardiovascular phenotype with an elevated 24-h heart rate, a decreased 24-h diastolic blood pressure, and an attenuation of the dark-light difference in blood pressure and heart rate. Locomotor activity was similar in both groups and did not appear to explain the observed hemodynamic differences. When mice were placed under constant darkness during eight consecutive days, wild-type mice maintained 24-h rhythms, whereas there was an apparent progressive loss of 24-h rhythm of blood pressure, heart rate, and locomotor activity in mutant mice. However, a chi square periodogram revealed that circadian rhythms were preserved under complete absence of any light cue, but with shorter periods by approximately 40 min, leading to a cumulative phase shift toward earlier times of approximately 5 h and 20 min by the end of the 8th day. When heart rate, mean arterial pressure, and activity were recalculated according to the endogenous circadian periods of each individual mouse, the amplitudes of the circadian rhythms ("subjective night"-"subjective day" differences) were maintained for all variables studied. Our data show that mutation of the Period2 gene results in an attenuated dipping of blood pressure and heart rate during both light-dark cycles and constant darkness, and in shorter circadian periods during constant darkness.
昼夜血压模式的改变在高血压中经常观察到,并导致心血管发病率增加。然而,目前还没有研究探讨 Period2 基因(分子生物钟的关键组成部分)对血压和心率昼夜节律的可能影响。为了解决这个问题,我们通过遥测术在携带 Period2 基因突变的小鼠和野生型对照小鼠中 24 小时监测血压、心率和活动。在标准的 12:12 小时光照-黑暗周期下,突变小鼠表现出轻微的心血管表型,24 小时心率升高,24 小时舒张压降低,血压和心率的明暗差异减弱。两组的活动情况相似,似乎并未解释所观察到的血液动力学差异。当小鼠连续 8 天置于连续黑暗中时,野生型小鼠维持 24 小时节律,而突变型小鼠的血压、心率和活动的 24 小时节律明显丧失。然而,卡方周期图显示,在没有任何光照线索的情况下,昼夜节律仍然存在,但周期缩短了约 40 分钟,导致到第 8 天结束时,大约提前 5 小时 20 分钟的累积相位偏移。当根据每个个体小鼠的内源性昼夜周期重新计算心率、平均动脉压和活动时,所有研究变量的昼夜节律幅度(“主观夜间”-“主观白天”差异)得以维持。我们的数据表明,Period2 基因突变导致在光照-黑暗周期和连续黑暗期间血压和心率的下降减弱,并且在连续黑暗期间昼夜周期变短。