Optimizing cerebrovascular endothelial health through shear stress modulation

Abstract

The endothelium plays a pivotal role in regulating cerebrovascular blood flow, and its dysfunction increases the risk of cerebrovascular disease. Endothelial shear stress, a primary mechanical stimulus for endothelial nitric oxide production, is a key modulator of vascular adaptation. In recent years, transient hypercapnia-induced flow-mediated dilation of the internal carotid artery (ICA-FMD) has emerged as a valuable in vivo approach for assessing cerebrovascular endothelial function in humans. This review first synthesizes methodological advances in ICA-FMD assessment, emphasizing the importance of transient carbon dioxide (CO2) inhalation, normalizing ICA-FMD to the shear stress, and consideration of unique ICA haemodynamics. Second, it consolidates mechanistic insights and conditions for improving ICA-FMD, elucidating effective and ineffective strategies. Intermittent hypoxia-induced increases in shear stress improve ICA dilatory response, underscoring the pivotal role of shear rate. Although ICA blood flow during exercise has been extensively studied, data on shear rate during exercise are limited. Moderate-intensity leg cycling that avoids hyperventilation and elevates end-tidal CO2 partial pressure increases ICA shear rate and augments post-exercise ICA-FMD, whereas higher-intensity exercise or small-muscle exercise fails to produce similar benefits. These observations suggest that a threshold shear stimulus may be required for post-exercise improvements in ICA-FMD. Future research should establish standardized methodologies, define the shear stimulus threshold, elucidate the time course of vascular adaptations, and extend investigations to populations at elevated cerebrovascular risk. Translating these mechanistic insights into clinical strategies has the potential to optimize cerebrovascular endothelial function and thereby contribute to the prevention of cerebrovascular diseases.