Combined renal denervation and adrenal ablation enhance blood pressure reduction in spontaneously hypertensive rats

Renal denervation (RDN) is an established interventional therapy for resistant hypertension, but its antihypertensive efficacy remains modest and heterogeneous. Compensatory adrenal activation may limit the blood pressure response to sympathetic denervation alone. Whether simultaneous targeting of renal sympathetic and adrenal neurohumoral pathways enhances blood pressure reduction has not been investigated. Male spontaneously hypertensive rats (SHRs) underwent sham operation, RDN alone, adrenal ablation alone, or combined RDN and adrenal ablation. Blood pressure was assessed by radiotelemetry over 12 weeks. RDN alone, adrenal ablation alone, and combined treatment significantly reduced blood pressure in SHRs. Combined treatment produced the greatest reductions in systolic, diastolic, and mean arterial pressure. Lumbar sympathetic nerve activity and plasma norepinephrine levels were further suppressed in the combined-treatment group compared with either monotherapy. Combined intervention also more effectively attenuated cardiac hypertrophy and glomerulosclerosis, while improving left ventricular function. Heart rate reduction was primarily associated with RDN. Importantly, stress-induced corticosterone and adrenocorticotropic hormone responses remained detectable following combined treatment. Combined RDN and adrenal ablation produced greater sustained antihypertensive effects, sympathetic suppression, and target organ protection in male SHRs. These findings support simultaneous modulation of renal sympathetic and adrenal neurohumoral pathways as a potential multi-organ interventional strategy for hypertension.