Non-Invasive Ultrasound Modulation of Solitary Tract Nucleus Exerts a Sustainable Antihypertensive Effect in Spontaneously Hypertensive Rats

OBJECTIVE: We applied the method of non-invasive ultrasound (US) neuromodulation to regulate blood pressure (BP) by stimulating the solitary tract nucleus (NTS) of spontaneously hypertensive rats (SHRs). METHODS: The rats were exposed to US stimulation for 20 mins every day for two months. Morphology and function of the hypertensive target organs (heart and kidney) were then examined by echocardiography and immunohistochemical staining. C-fos immunofluorescence assays were used to evaluate neuronal activity in the US stimulated areas and to explore related neural pathways. Moreover, the effects of US stimulation on biochemical indicators angiotensinII (ANGII), aldosterone (Aldo), endothelin-1 (ET-1), atrial natriuretic factor (ANF), cortisol (Cor) in SHRs were detected. In addition, HE, TUNEL, and Nissl staining were performed to evaluate the safety of long-term transcranial US stimulation. RESULTS: After two months of US stimulation, systolic blood pressure (SBP) decreased from 170 ± 1.1 mmHg to 158 ± 1.8 mmHg, p < 0.01. What's more, US stimulation effectively inhibited the pathological process of target organs from both morphological and functional levels. With US stimulation, neuronal activities were also significantly enhanced in the NTS, ventrolateral periaqueductal gray (vlPAG), and the caudal ventrolateral medulla (CVLM) region. And US stimulation did not cause brain tissue damage. Meanwhile, the plasma levels of ANF, ANGII, Aldo, and Cor content were inhibited. CONCLUSION: US stimulation of the NTS could significantly lower BP in SHRs. SIGNIFICANCE: Non-invasive transcranial US stimulation acting on the NTS might be a potential therapeutic intervention due to its efficacy and safety.