Abstract
Hypertension (HTN) affects over 1 billion people in the world, and while most are treated effectively with pharmacological regimens, 10–30% of them do not show a beneficial response. Electrical stimulation of the renal sympathetic, vagus and carotid sinus nerves has shown depressor effects and has been proposed as an alternative treatment for resistant hypertension (R-HTN). However, these nerves are heterogeneous in afferent/efferent composition, and their stimulation often results in unwanted side effects. We evaluated the possibility of eliciting a depressor response from stimulation of single fascicle of the somatic deep peroneal nerve (fDPN). A microchannel electrode array (µCEA) was used to stimulate the fDPN at low frequency, which induced a significant (p ≤ 0.03) transient reduction in mean arterial pressure (MAP) with no significant effects on heart rate. The depressor response was prolonged for several hours by extending the fDPN stimulation to 5 min, which induced significant reduction (17–25%) in MAP for up to 4 h. Immunofluorescence evaluation of the axonal marker, myelin, and active macrophages in the fDPN revealed no indication of nerve damage or overt inflammation in response to the procedure. This study provides evidence supporting the use of µCEA interfacing of small somatic nerve fascicles associated with cardiovascular relevant acupoints to induce significant reductions in MAP and opens the possibility of neuromodulation of small fascicles as an alternative strategy to treat R-HTN with minimal side effects. Further, the µCEA multielectrode array offers an effective tool for neuromodulation of small nerve fascicles, enabling a number of possible future medical bioelectronic applications.
Highlights
Hypertension (HTN) affects over 1 billion people around the world [1]
We demonstrate that a significant reduction in mean arterial pressure (MAP) in hypertensive rats can be achieved through microelectrical stimulation of a somatic nerve fascicle for up to 4 h without significantly altering heart rate (HR)
The baseline MAP and HR in normotensive WKY and hypertensive SHR rats was of 128.83 ± 41 and 149.75 ± 35 mmHg and 400.2 ± 38 and 350 ± 83 bpm, respectively
Summary
Hypertension (HTN) affects over 1 billion people around the world [1]. Appropriate dosing is challenging because of the high variability in the patient response, narrow therapeutically acceptable range, adverse reactions and toxicity [3]. Approximately 10–30% of the affected population is resistant to pharmacological treatments, despite the use of combinatorial drug treatments and maximum doses [4,5]. Individuals suffering from resistant hypertension (R-HTN) have high rates of cardiovascular complications and few treatment options. Some promising research candidates for the treatment of R-HTN such as renal artery denervation have failed to show efficacy [6,7]. There is much need for developing alternative methods for R-HTN regulation
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