Research progress on neurohumoral mechanism and clinical significance of vasovagal syncope

Vasovagal syncope (VVS) is the most common type of syncope in clinical practice, primarily caused by the excessive response of the autonomic nervous system to external stimuli, leading to vasodilation and bradycardia, and consequently reduced whole brain perfusion. At present, the pathophysiological mechanism of VVS remains largely unknown, with neurohumoral regulation playing a significant role in it. Sympathetic Nervous System (SNS) plays a crucial role in the occurrence of VVS by regulating heart rate, blood pressure and vascular tone, especially in blood pressure regulation, postural changes, and stress response. The Renin-Angiotensin-Aldosterone System (RAAS) maintains blood volume and blood pressure stability by regulating vasoconstriction and sodium and water retention. Nitric oxide (NO) and hydrogen sulfide (H2S) secreted by vascular endothelial cells as vasodilator factors, and Endothelin (ET) as vasoconstrictor factors, are involved in regulating vascular tone. Neurotransmitters such as 5-hydroxytryptamine (5-HT) and galanin also play a key role in the occurrence of VVS. SNS and RAAS are involved in the occurrence of VVS. When the hemodynamics is still in a stable state, the plasma Epi and NE concentrations increase, and the Epi increment is much higher than NE, resulting in an increase in Epi/NE value. The significant β-adrenergic effect leads to peripheral vasodilation, venous blood flow accumulation, and progressive blood pressure decline, which is the most important pathophysiological mechanism leading to syncope. When hypotension occurs, the body compensatively secretes a large amount of AVP, and the significant increase of AVP concentration further leads to vasodilation, aggravates the decrease of blood pressure, and causes syncope. In the future, more accurate VVS drug development will become the focus. Using modern pharmacology and molecular biology techniques, drugs targeting specific neurohumoral mechanisms will be developed to achieve higher efficacy with fewer side effects. Additionally, the identification and validation of new biomarkers will drive advancements in early diagnosis and monitoring of treatment outcomes.