Abstract
Targeting the carotid body (CB) is a new approach in treating hypertension. This study investigates the efficacy and safety of ultrasound combined with microbubbles in targeting CB to treat hypertension. Twenty-seven hypertensive rabbits were randomly assigned to three groups: microbubbles only (sham group, n = 11), ultrasound plus microbubbles (LIFU group, n = 11), and bilateral carotid sinus nerve denervation (CSND group, n = 5). Four weeks post-intervention, blood pressure, hypoxic ventilatory response (HVR), blood pressure variability (BPV), heart rate variability (HRV), biochemical indicators, neurohormones, and histopathology were assessed in all groups. The results indicated significant reductions in systolic and diastolic blood pressure in the LIFU and CSND groups post-intervention, along with decreases in BPV, HRV, and catecholamines. HVR results showed a 35.10% reduction in CB activity in the LIFU group compared to the sham group, which was significantly lower than the reduction in the CSND group compared to the sham group (73.85%). Histopathology and transmission electron microscopy confirmed CB damage and cell apoptosis, with immunofluorescence showing a reduction in type I and II cells. In conclusion, LIFU combined with microbubbles can reduce blood pressure by lowering CB and sympathetic nerve activity.
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Data availability
The data for this study are available upon reasonable request to the corresponding author.
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Acknowledgements
We thank the Chongqing Key Laboratory of Ultrasound Molecular Imaging (Chongqing Medical University) for their support. We thank all the members of the laboratory, especially Dr Yang Cao, for their technical assistance in the use of LIFU-mediated ultrasound cavitation.
Funding
The work was supported by National Natural Science Foundation of China (No. 82170445, 81370440 and 81900361), and partly by Major Scientific Instrument Development Project of the National Natural Science Foundation of China (32127802), the National Science-Technology Support Projects of China (No. 2015BAI01B00) and Encouraged Scientific Research Projects of Health Commission of Mianyang City (202248).
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JH conceived and designed the study. WY and XJ performed data analysis as well as wrote the manuscript. WY and XJ performed the experiments and collected the data. ZC, YX, HG helped with ultrasound localization and assessment. CL and XL assisted in the establishment of the animal model. JQ, BX and SR assisted in the improvement of equipment for measuring the response to hypoxic ventilation; GC and QS guided the optimization of carotid body ultrasound intervention methods. FL helped with histopathological examination. All authors read and approved the final manuscript.
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This experimental study was approved by the Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University (permit number: (2021)347).
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Jiang, X., Yu, W., Chen, Z. et al. Low-intensity focused ultrasound combined with microbubbles for non-invasive downregulation of rabbit carotid body activity in the treatment of hypertension. Hypertens Res 47, 3182–3192 (2024). https://doi.org/10.1038/s41440-024-01904-3
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DOI: https://doi.org/10.1038/s41440-024-01904-3
