Antihypertensive effect of brain-targeted mechanical intervention with passive head motion

Nervous cell functions are known to be physiologically regulated by mechanical factors in the brain. However, it remains unclear whether mechanical interventions can modulate the pathophysiological processes underlying brain-related disorders and modify their consequences. Here we show that passive head motion of hypertensive rats, which reproduces mechanical accelerations generated at their heads during treadmill running at a moderate velocity, decreases the expression of angiotensin II type 1 receptor (AT1R) in astrocytes in their rostral ventrolateral medulla (RVLM). This decrease results in lowering their blood pressure. Passive head motion generates interstitial fluid movement that is estimated to exert shear stress with average magnitude of a few Pa on cells in rats’ brainstem. Fluid shear stress of a relevant magnitude decreases AT1R expression in cultured astrocytes, but not in neuronal cells. Furthermore, in hypertensive rats, inhibition of movement of interstitial fluid by its gelation with reactive polyethylene glycol injected into the RVLM eliminates the ability of passive head motion to decrease their blood pressure and AT1R expression in RVLM astrocytes. Consistent with these results from animal experiments, vertically oscillating chair riding of hypertensive adult humans, which reproduces mechanical accelerations generated at their heads during light jogging or fast walking, lowers their blood pressure. Our findings indicate that moderate mechanical impact on the head has an antihypertensive effect by modulating the function of RVLM astrocytes through interstitial fluid shear stress. We anticipate mechanical regulation to underlie a variety of positive effects of physical exercise on human health, particularly those related to brain functions.