Abstract 9243: Brain-Targeted Mechanical Intervention Using Passive Head Motion Can Have an Antihypertensive Effect

Introduction: Exercise is known to be effective as a therapeutic/preventative measure for numerous physical disorders and diseases including hypertension. However, the mechanisms underlying the antihypertensive effect of exercise remain to be elucidated. Hypothesis: The positive effects of exercise may be mediated by mechanical forces generated during exercise activities. Exercise-mimicking mechanical intervention may have an antihypertensive effect. Methods: We conducted animal experiments in which we reproduced mechanical accelerations generated in the head during moderate-velocity running. 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 (PHM) in hypertensive rats, which reproduced the mechanical accelerations generated in their heads during moderate-velocity treadmill running, decreased the expression of angiotensin II type 1 receptor (AT1R) in astrocytes in the rostral ventrolateral medulla (RVLM), thereby lowering their blood pressure. PHM generated interstitial fluid movement that was estimated to exert shear stress with an average magnitude of <1 Pa on the cells in the rat medulla. Fluid shear stress of a sub-Pa magnitude decreased the AT1R expression in cultured astrocytes. Inhibition of interstitial fluid movement following hydrogel introduction to the RVLM eliminated the antihypertensive effects of PHM and treadmill running. 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 have an antihypertensive effect by modulating the function of RVLM astrocytes through interstitial fluid shear stress.