Autonomic nervous system: an integrative regulator in circadian rhythm of blood pressure

Figures

• 

  Figure 1. Systematic organization of circadian clocks and BP regulation under physiological conditions. This figure illustrates the hierarchical organization of circadian clocks. The suprachiasmatic nucleus (SCN), located in the hypothalamus, serves as the central clock, receiving external time cues (Zeitgebers) such as light (via the retina), sleep, and daily diet. The SCN then synchronizes peripheral clocks located in various organs (e.g., heart, kidneys) through both neural pathways [involving the autonomic nervous system (ANS)] and humoral pathways (e.g., hormonal signals from the pituitary gland). The ANS, comprising the sympathetic and parasympathetic systems, plays a crucial role in transmitting circadian signals to peripheral organs, thereby influencing blood pressure (BP) rhythms. Under physiological conditions, these synchronized clocks ensure that BP exhibits a characteristic diurnal variation (higher during the day, lower at night). This systematic regulation ensures the body’s physiological functions, including BP, are aligned with the earth’s 24-h day/night cycle.

• 

  Figure 2. Cellular organization of circadian clocks and molecular regulation of BP. This figure illustrates the molecular mechanisms underlying circadian rhythms within individual cells, which constitute the peripheral clocks. At the core is the transcription-translation feedback loop (TTFL), a self-regulated system involving key clock proteins. Specifically, Clock and Bmal1 heterodimers (TFs) positively regulate the expression of Cry and Per genes at the beginning of a day. As Cry and Per proteins accumulate, they dimerize and subsequently inhibit the expression of Bmal1 and Clock. This cyclical inhibition and activation lead to the oscillation of these TFs throughout the day. These oscillating clock proteins then bind to E-boxes (enhancer box elements) in the promoters of clock-controlled genes (CCGs), thereby regulating their rhythmic expression. These CCGs are involved in diverse physiological processes, including metabolism (e.g., lipid, glucose regulation), immune response and the secretion of neurotransmitters and hormones. These molecular oscillations within peripheral clocks, particularly in organs like the heart and vessels, contribute to the circadian variation of blood pressure…

• 

  Figure 3. Disruption of circadian clocks and autonomic nervous system (ANS) activity by environmental cues in pathological conditions. This figure illustrates how various environmental disruptions initiate the pathological cascade leading to abnormal blood pressure (BP) patterns. External circadian time cues, such as abnormal light exposure or night shift work (affecting the natural light–dark cycle and sleep patterns) and unhealthy diet (e.g., high-salt, high-fat, or mistimed feeding), act as primary disruptors. These cues directly or indirectly impact the suprachiasmatic nucleus (SCN), the central clock, and subsequently perturb the synchronization of peripheral clocks located in various organs throughout the body. A critical consequence of these disrupted circadian signals is the disorder of ANS activity. This typically involves an imbalance between the sympathetic and parasympathetic nervous systems, often characterized by increased sympathetic tone and/or reduced parasympathetic modulation. This ANS dysregulation is a central mediator linking environmental disruptions to the development of hypertension. The overall effect is a deviation from the normal physiological BP rhythm, setting…

• 

  Figure 4. Therapeutic strategies modulating the autonomic nervous system (ANS) for hypertension. This figure outlines the therapeutic strategies for hypertension through modulation of the autonomic nervous system (ANS), summarizing the mechanisms of current and prospective treatments. These strategies are categorized into four main groups: first, lifestyle modifications, which encompass treating obstructive sleep apnea syndrome (OSAS) with continuous positive airway pressure (CPAP) to rebalance the ANS and improve blood pressure (BP) control, adopting the Dietary Approaches to Stop Hypertension (DASH) diet rich in fruits/vegetables and low in saturated fats to modulate the intestinal sympathetic nervous system, and employing time-restricted feeding (TRF) to inhibit sympathetic activity and enhance insulin sensitivity; second, pharmacological chronotherapy, which optimizes the timing of antihypertensive medication administration (e.g., before sleep) to target circadian BP fluctuations and ANS activity for enhanced efficacy; third, interventional treatment via catheter-based renal denervation (RDN), a minimally invasive procedure that ablates renal sympathetic nerves to reduce SNS activity…