Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California 90024, USA.
Am J Physiol Heart Circ Physiol. 2011 Jan;300(1):H241-50. doi: 10.1152/ajpheart.00190.2010. Epub 2010 Oct 15.
The circadian system, driven by the suprachiasmatic nucleus (SCN), regulates properties of cardiovascular function. The dysfunction of this timing system can result in cardiac pathology. The neuropeptide vasoactive intestinal peptide (VIP) is crucial for circadian rhythms in a number of biological processes including SCN electrical activity and wheel running behavior. Anatomic evidence indicates that SCN neurons expressing VIP are well positioned to drive circadian regulation of cardiac function through interactions with the autonomic centers. In this study, we tested the hypothesis that loss of VIP would result in circadian deficits in heart rate (HR) and clock gene expression in cardiac tissue. We implanted radiotelemetry devices into VIP-deficient mice and wild-type (WT) controls and continuously recorded HR, body temperature, and cage activity in freely moving mice. Under light-dark conditions, VIP-deficient mice displayed weak rhythms in HR, body temperature, and cage activity, with onsets that were advanced in phase compared with WT mice. Similarly, clock gene expression in cardiac tissue was rhythmic but phase advanced in mutant mice. In constant darkness, the normal circadian rhythms in HR were lost in VIP-deficient mice; however, most mutant mice continued to exhibit circadian rhythms of body temperature with shortened free-running period. The loss of VIP altered, but did not abolish, autonomic regulation of HR. Analysis of the echocardiograms did not find any evidence for a loss of cardiac function in VIP-deficient mice, and the size of the hearts did not differ between genotypes. These results demonstrate that VIP is an important regulator of physiological circadian rhythmicity in the heart.
昼夜节律系统受视交叉上核（SCN）驱动，调节心血管功能特性。该计时系统的功能障碍可导致心脏病变。神经肽血管活性肠肽（VIP）对于包括 SCN 电活动和轮跑行为在内的许多生物过程的昼夜节律至关重要。解剖学证据表明，表达 VIP 的 SCN 神经元通过与自主中枢的相互作用，很好地驱动了心脏功能的昼夜节律调节。在这项研究中，我们检验了 VIP 缺失会导致心脏率（HR）和时钟基因表达出现昼夜节律缺陷的假设。我们将无线电遥测装置植入 VIP 缺失小鼠和野生型（WT）对照小鼠体内，并在自由活动的小鼠中连续记录 HR、体温和笼内活动。在明暗条件下，VIP 缺失小鼠的 HR、体温和笼内活动节律较弱，与 WT 小鼠相比，相位提前。同样，心脏组织中的时钟基因表达也呈节律性，但在突变小鼠中相位提前。在持续黑暗中，VIP 缺失小鼠的 HR 正常昼夜节律丧失；然而，大多数突变小鼠仍表现出体温的昼夜节律，自由运行周期缩短。VIP 的缺失改变了，但没有消除，HR 的自主调节。超声心动图分析并未发现 VIP 缺失小鼠心脏功能丧失的任何证据，两种基因型的心脏大小也没有差异。这些结果表明，VIP 是心脏生理昼夜节律的重要调节因子。
