(51) Renal Nerve Stimulation: Frequency-Dependent Effects on Renal Blood Flow

Introduction: Despite the availability of safe and effective high-blood pressure medications, many people struggle to control their hypertension. Drug-resistant hypertension has been linked to persistent overactivity of the renal nerves, resulting in decreased renal blood flow, which makes hypertension regulation difficult to control. Recent therapeutic strategies show that catheter-based renal denervation (RDN) successfully lowers arterial pressure in hypertensive patients by interfering with the brain-kidney link, which reduces central sympathetic outflow. However, a critical drawback associated with RDN is its irreversibility and lack of adaptability over time. Animal studies have suggested the potential reconnection of renal nerves, prompting the need for alternative strategies.

Methods: Addressing this concern, our study explores the application of kilohertz-frequency trains of electrical stimulation as a promising approach to inhibit nerve activity to the kidneys. In this investigation, we explored the effects of electrical stimulation on renal nerves utilizing an acute non-diseased swine model. Using hook electrodes around the renal artery-nerve complex, we performed a preliminary study to investigate how stimulation frequency (5Hz -15kHz) and stimulation current (1 – 6 mA) affect hemodynamics through the kidney by measuring blood flow in the renal vein. Data processing involved noise filtering, peak extraction, and mean values analysis to assess the percentage change in blood flow during stimulation. Statistical comparisons were performed using the Wilcoxon signed-rank test.

Results: Our results demonstrate a nonlinear, frequency-dependent response in renal blood flow.
• Low-frequency ( < 100 Hz) stimulation consistently reduced blood flow—with the strongest effects at 20–50 Hz and sustained inhibition.
• High-frequency stimulation (>100 Hz) induced an initial reduction in blood flow, followed by a gradual return to baseline values, indicative of habituation during prolonged stimulation. Temporal analysis revealed minimal change of –1.74% ± 0.99% at 20 Hz versus an 8.20% ± 0.86% recovery at 200 Hz.
• KFS induced a carryover effect, where subsequent low-frequency stimulation resulted in a diminished reduction in blood flow. Low-frequency stimulation before KFS produced a mean blood flow reduction of –16.45% ± 1.54%, which was significantly attenuated to –10.59% ± 1.57% post-KFS (p = 0.003), suggesting that KFS modulates nerve activity in a way that alters future stimulation effects.

Conclusion: These observations suggest a complex interplay between different stimulation frequencies, highlighting the need for further exploration into the dynamic responses of renal nerves to electrical stimulation. Our results hold promise for the development of targeted and efficient strategies to address drug-resistant hypertension using kidney neuromodulation.