PS-B07-1: BRAIN-TARGETED MECHANICAL INTERVENTION USING PASSIVE HEAD MOTION CAN BE ANTIHYPERTENSIVE

Abstract

Objective: Reproduce the antihypertensive effect of physical exercise by applying mechanical intervention. Design and method: We conducted animal experiments in which we reproduced mechanical accelerations generated in the head during treadmill running at a moderate velocity. We performed in vitro experiments using cultured cells to determine what type of mechanical force was responsible for the antihypertensive effect of mechanical intervention. We carried out clinical studies to validate the clinical relevance of our findings. Results: Passive head motion in hypertensive rats, which reproduced the mechanical accelerations generated in their heads during treadmill running at a moderate velocity, decreased the expression of angiotensin II type 1 receptor (AT1R) in astrocytes in the rostral ventrolateral medulla (RVLM). This decrease resulted in lowering their blood pressure. Passive head motion generated interstitial fluid movement, which was estimated to exert shearing forces with an average magnitude of < 1 Pa on the cells in the rat medulla. Application of fluid shear stress of relevant magnitudes decreased the AT1R expression in cultured astrocytes, but not in neuronal cells. Furthermore, interference with interstitial fluid movement by hydrogel introduction in the RVLM of hypertensive rats eliminated the ability of passive head motion and treadmill running to decrease their blood pressure and AT1R expression in the RVLM astrocytes. Consistent with these results from animal experiments, vertically oscillating chair riding by hypertensive adult humans, which reproduced the mechanical accelerations generated in their heads during light jogging, lowered their blood pressure. Conclusion: Brain-targeted mechanical intervention can be antihypertensive by modulating the function of RVLM astrocytes through interstitial fluid shear stress.