PT - JOURNAL ARTICLE AU - Shuhei Murase AU - Naoyoshi Sakitani AU - Takahiro Maekawa AU - Daisuke Yoshino AU - Ayumu Konno AU - Hirokazu Hirai AU - Taku Saito AU - Sakae Tanaka AU - Keisuke Shinohara AU - Takuya Kishi AU - Yuki Yoshikawa AU - Takamasa Sakai AU - Makoto Ayaori AU - Hirohiko Inanami AU - Koji Tomiyasu AU - Toru Ogata AU - Atsushi Takashima AU - Masahiro Shinohara AU - Motoshi Nagao AU - Yasuhiro Sawada TI - Mechanical impact on the head has an antihypertensive effect AID - 10.1101/2020.09.21.305706 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.09.21.305706 4099 - http://biorxiv.org/content/early/2020/09/21/2020.09.21.305706.short 4100 - http://biorxiv.org/content/early/2020/09/21/2020.09.21.305706.full AB - 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.Competing Interest StatementThe authors have declared no competing interest.