The sustainable antihypertensive and target organ damage protective effect of transcranial focused ultrasound stimulation in spontaneously hypertensive rats
Dapeng Li, Fangyuan Cao, Jie Han, Mengke Wang, Chunhao Lai, Jingjing Zhang, Tianqi Xu, Ayache Bouakaz, Mingxi Wan, Pengyu Ren, Siyuan Zhang
Journal of Hypertension 2023 · 10.1097/hjh.0000000000003407
Abstract
Objective In this study, we aimed to investigate the sustainable antihypertensive effects and protection against target organ damage caused by low-intensity focused ultrasound (LIFU) stimulation and the underlying mechanism in spontaneously hypertensive rats (SHRs) model. Methods and results SHRs were treated with ultrasound stimulation of the ventrolateral periaqueductal gray (VlPAG) for 20 min every day for 2 months. Systolic blood pressure (SBP) was compared among normotensive Wistar-Kyoto rats, SHR control group, SHR Sham group, and SHR LIFU stimulation group. Cardiac ultrasound imaging and hematoxylin-eosin and Masson staining of the heart and kidney were performed to assess target organ damage. The c-fos immunofluorescence analysis and plasma levels of angiotensin II, aldosterone, hydrocortisone, and endothelin-1 were measured to investigate the neurohumoral and organ systems involved. We found that SBP was reduced from 172 ± 4.2 mmHg to 141 ± 2.1 mmHg after 1 month of LIFU stimulation, P Conclusion We concluded that LIFU stimulation has a sustainable antihypertensive effect and protects against target organ damage by activating antihypertensive neural pathways from VLPAG to the caudal ventrolateral medulla and further inhibiting the renin-angiotensin system (RAS) activity, thereby supporting a novel and noninvasive alternative therapy to treat hypertension.
Abstract via europepmc.
Exposures
Exposure 1: LIFU to VLPAG, 20 min daily for 2 months
Target: periaqueductal gray — “ventrolateral periaqueductal gray (VlPAG)”
Device: other named manufacturer · Chongqing Haifu Medical Technology Co., Ltd ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 620 | ✓✓✓ |
| Pulse duration (ms) | 2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 250 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓⚑ |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | 630 | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | 12.74 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 6.37 | ✓✓✓ |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 320 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 3.28 | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 1.64 | ✓✓✓ |
PRF 250 Hz, 2 ms tone-burst duration, 200 ms sonication duration and 5 s inter stimulation interval; stimulation for 20 min each day for 2 months. The Sham group received the same stimulation focused on the motor cortex.
Flags from extraction
n_subjects— Four groups of 8 (WKY, SHR, Sham, LIFU); only Sham and LIFU were sonicated, so group sizes listed; no total of exposed animals stated. c-fos and histology used 5 per group.exposures[0].free_field.pressure_kpa— Text gives negative peak pressure 0.63 MPa; recorded as 630 kPa.exposures[0].in_situ.pressure_kpa— Sentence is garbled in the text (symbols lost); 0.32 MPa in situ after 50% attenuation measured through an ex vivo rat skull. Method recorded as derating.exposures[0].in_situ.isppa_w_cm2— Intensity symbols are missing from the sentence (reads 'the I in the brain was 3.28 ... the I was 1.64'); assigned to Isppa and Ispta by order, consistent with the free-field values halved in pressure.exposures[0].timing.duty_cycle_pct— Duty cycle 50% given in the text; 2 ms TBD and 250 Hz PRF are given in the figure legend.exposures[0].device.family— Manufacturer of transducer named; model not given.anaesthesia— Isoflurane during stimulation; blood pressure measured in conscious rats.