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Mechanical impact on the head has an antihypertensive effect

Shuhei Murase, Naoyoshi Sakitani, Takahiro Maekawa, Daisuke Yoshino, Ayumu Konno, Hirokazu Hirai, Taku Saito, Sakae Tanaka, Keisuke Shinohara, Takuya Kishi, Yuki Yoshikawa, Takamasa Sakai, Makoto Ayaori, Hirohiko Inanami, Koji Tomiyasu, Toru Ogata, Atsushi Takashima, Masahiro Shinohara, Motoshi Nagao, View ORCID ProfileYasuhiro Sawada
doi: https://doi.org/10.1101/2020.09.21.305706
Shuhei Murase
1Department of Rehabilitation for Motor Functions, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan
2Department of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Naoyoshi Sakitani
1Department of Rehabilitation for Motor Functions, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan
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Takahiro Maekawa
1Department of Rehabilitation for Motor Functions, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan
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Daisuke Yoshino
3Division of Advanced Applied Physics, Institute of Engineering, Tokyo University of Agriculture and Technology, Koganei, Japan
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Ayumu Konno
4Department of Neurophysiology & Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Japan
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Hirokazu Hirai
4Department of Neurophysiology & Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Japan
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Taku Saito
2Department of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Sakae Tanaka
2Department of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Keisuke Shinohara
5Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
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Takuya Kishi
6Department of Cardiology, Graduate School of Medicine, International University of Health and Welfare, Okawa, Japan
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Yuki Yoshikawa
7Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
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Takamasa Sakai
7Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
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Makoto Ayaori
8Tokorozawa Heart Center, Tokorozawa, Japan
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Hirohiko Inanami
9Inanami Spine & Joint Hospital/Iwai Orthopaedic Medical Hospital, Iwai Medical Foundation, Tokyo, Japan
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Koji Tomiyasu
10Department of Internal Medicine, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan.
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Toru Ogata
1Department of Rehabilitation for Motor Functions, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan
11Center of Sports Science and Health Promotion, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan.
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Atsushi Takashima
12Department of Assistive Technology, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan.
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Masahiro Shinohara
1Department of Rehabilitation for Motor Functions, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan
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Motoshi Nagao
1Department of Rehabilitation for Motor Functions, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan
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Yasuhiro Sawada
1Department of Rehabilitation for Motor Functions, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan
13Department of Clinical Research, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Japan.
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  • ORCID record for Yasuhiro Sawada
  • For correspondence: ys454-ind@umin.ac.jp
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Abstract

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 Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 21, 2020.
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Mechanical impact on the head has an antihypertensive effect
Shuhei Murase, Naoyoshi Sakitani, Takahiro Maekawa, Daisuke Yoshino, Ayumu Konno, Hirokazu Hirai, Taku Saito, Sakae Tanaka, Keisuke Shinohara, Takuya Kishi, Yuki Yoshikawa, Takamasa Sakai, Makoto Ayaori, Hirohiko Inanami, Koji Tomiyasu, Toru Ogata, Atsushi Takashima, Masahiro Shinohara, Motoshi Nagao, Yasuhiro Sawada
bioRxiv 2020.09.21.305706; doi: https://doi.org/10.1101/2020.09.21.305706
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Mechanical impact on the head has an antihypertensive effect
Shuhei Murase, Naoyoshi Sakitani, Takahiro Maekawa, Daisuke Yoshino, Ayumu Konno, Hirokazu Hirai, Taku Saito, Sakae Tanaka, Keisuke Shinohara, Takuya Kishi, Yuki Yoshikawa, Takamasa Sakai, Makoto Ayaori, Hirohiko Inanami, Koji Tomiyasu, Toru Ogata, Atsushi Takashima, Masahiro Shinohara, Motoshi Nagao, Yasuhiro Sawada
bioRxiv 2020.09.21.305706; doi: https://doi.org/10.1101/2020.09.21.305706

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