BackgroundPerivascular spaces (PVS) are fluid-filled spaces that functions as channels for glymphatic clearance in the brain. Enlarged perivascular spaces (ePVS) have been associated with high blood pressure. Hypertension features abnormal increases in muscle sympathetic nerve activity (MSNA), which constricts blood vessels in the muscle vascular bed, but the underlying mechanisms for this increase are not understood. Moreover, the association between ePVS and the resting sympathetic outflow from the brain has not been studied in normotensive or hypertensive humans. Therefore, we assessed whether ePVS is associated with muscle sympathetic nerve activity (MSNA) in 25 hypertensive patients and 50 healthy normotensive adults.MethodsT1-weighted MRI anatomical brain images were analysed for ePVS using a deep learning-based segmentation algorithm – nnU-Net. ePVS in the white matter (WM), basal ganglia (BG), hippocampus (HP), and midbrain (MB) were analysed. Spontaneous bursts of MSNA were recorded from the right common peroneal nerve via a tungsten microelectrode immediately before the MRI scan.ResultsSignificant associations were found between ePVS and MSNA in the WM, BG, and HP in both the normotensive and hypertensive groups after adjusting for confounding factors (age, sex, mean blood pressure, total intracranial volume). However, the association between MSNA and MB ePVS was only observed in the hypertensive group.ConclusionThis finding provides insights into the pathophysiology of elevated sympathetic drive in hypertension.What is new?• Enlarged perivascular spaces (ePVS) are associated with muscle sympathetic nerve activity (MSNA) in normotensive and hypertensive humans.• Hypertensives and normotensives display differences in the association between the midbrain ePVS and MSNA.What are the clinical implications?• Insights into the centrally driven pathophysiological mechanism of elevated sympathetic nerve outflow in hypertension has been revealed.• ePVS may be used as an imaging biomarker for individuals with high sympathetic nerve activity, allowing identification of risk individuals that require microneurographic assessment of sympathetic nerve activity
