Renal Sympathetic Nervous System Overactivation and Its Contribution to Treatment-Resistant Hypertension: Mechanistic Evidence from a Nigerian University Hospital Cohort in Enugu State

Renal sympathetic nervous system overactivation is a proposed but insufficiently characterised mechanism contributing to treatment-resistant hypertension, particularly in high-sympathotonic African populations. This study investigated renal sympathetic overactivation and its mechanistic contribution to treatment-resistant hypertension in a Nigerian university hospital cohort, making an original mechanistic and translational contribution to hypertension physiology. A cross-sectional mechanistic design enrolled 90 patients at the University of Nigeria Teaching Hospital, Enugu, South East Nigeria, comprising 40 treatment-resistant hypertensives, 30 treatment-responsive hypertensives, and 20 normotensive controls. Renal sympathetic activity was estimated by 24-hour urine catecholamine excretion, spectral power analysis of heart rate variability, and I-123 metaiodobenzylguanidine cardiac imaging as a sympathetic innervation marker. Renal function was assessed by estimated glomerular filtration rate. Twenty-four-hour ambulatory blood pressure and plasma renin activity characterised cardiovascular phenotype. Path analysis and ANCOVA were applied. Results showed significantly elevated urinary noradrenaline excretion and sympathetic-to-parasympathetic heart rate variability ratio in treatment-resistant patients compared to both other groups. Metaiodobenzylguanidine uptake was reduced in treatment-resistant patients, indicating post-synaptic sympathetic desensitisation. Plasma renin activity was correlated with sympathetic activity. Renal function was modestly but significantly impaired in treatment-resistant patients. This study provides mechanistic evidence for renal sympathetic overactivation as a distinct physiological driver of treatment resistance in Nigerian patients, supporting renal denervation as a therapeutic target. Guidelines for sympatholytic therapy optimisation are proposed. Keywords: renal sympathetic, treatment-resistant hypertension, catecholamines, heart rate variability, Enugu.