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We applied low-intensity focused ultrasound (LIFU) stimulation of the ventrolateral periaqueductal gray (vlPAG) in spontaneously hypertensive rats (SHRs) model to demonstrate the feasibility of LIFU stimulation to decrease blood pressure (BP). The rats were treated with LIFU stimulation for 20 min every day for one week. The change of BP and heart rate (HR) were recorded to evaluate the antihypertensive effect. Then the plasma levels of epinephrine (EPI), norepinephrine (NE), and angiotensin II (ANGII) were measured to evaluate the activity of the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS). The c-fos immunofluorescence assay was performed to investigate the antihypertensive nerve pathway. Moreover, the biological safety of ultrasound sonication was examined. The LIFU stimulation induced a significant reduction of BP in 8 SHRs. The mean systolic blood pressure (SBP) was reduced from 170 ± 4 mmHg to 128 ± 4.5 mmHg after a one-week treatment, p < 0.01. The activity of SNS and RAS were also inhibited. The results of the c-fos immunofluorescence assay showed that US stimulation of the vlPAG significantly enhanced the neuronal activity both in vlPAG and caudal ventrolateral medulla (CVLM) regions. And the US stimulation used in this study did not cause significant tissue damage, hemorrhage and cell apoptosis in the sonication region. The results support that LIFU stimulation of the vlPAG could relieve hypertension in SHRs. The LIFU stimulation of the vlPAG could potentially be a new alternative non-invasive device therapy for hypertension.
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