Selective Renal Nerve Neuromodulation Produces Robust Antihypertensive Effects in Obesity-Induced Hypertension

Objective: Obesity-associated hypertension is increasingly prevalent and frequently resistant to pharmacological therapy, partly due to heightened sympathetic drive. The renal nerves play a central role in blood pressure (BP) regulation, making them an attractive target for device-based neuromodulation. Unlike renal denervation, renal nerve stimulation (RNS) offers a reversible and potentially safer strategy by engaging endogenous reflex pathways. Accordingly, this study aimed to evaluate the antihypertensive efficacy and renal hemodynamic effects of low-level RNS in a preclinical model of obesity-induced hypertension. Design and method: Thirteen anesthetized male Zucker fatty rats (ZFRs) underwent implantation of bipolar electrodes on the left renal nerve. RNS was delivered at low (2.5 Hz) and moderate (5.0 Hz) frequencies (0.5 mA, 0.5 ms, 30 s). Mean arterial pressure (MAP), heart rate (HR), hindquarter blood flow (HQF), and bilateral renal cortical perfusion (RCP) were continuously recorded. Hindquarter and renal cortical vascular resistances were calculated. Hemodynamic responses were compared across stimulation frequencies and between ipsilateral and contralateral kidneys. Results: Baseline MAP was elevated (115 ± 5 mmHg), confirming hypertension. RNS at both frequencies produced rapid and significant reductions in MAP (∼30 mmHg; ∼25%) without significant changes in HR. BP lowering was accompanied by increased HQF and marked reductions in hindquarter vascular resistance, indicating systemic vasodilation. Ipsilateral RCP decreased at both frequencies, with a greater reduction at 5.0 Hz; however, renal cortical resistance declined bilaterally, suggesting preserved renal autoregulation rather than vasoconstriction. Contralateral renal hemodynamic changes were modest and consistent with reflex-mediated systemic effects. Importantly, the 2.5 Hz protocol achieved BP reductions comparable to 5.0 Hz while exerting minimal impact on renal perfusion. Conclusions: Low-level RNS elicits robust antihypertensive effects in obesity-induced hypertension through reflex vasodilation while adequately preserving renal vascular integrity. These findings support low-frequency renal neuromodulation as a promising, titratable alternative to renal denervation for the treatment of obesity-related and potentially resistant hypertension.