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Roles of Sinusoidal Endothelial Cells in the Local Regulation of Hepatic Sinusoidal Blood Flow—Involvement of Endothelins and Nitric Oxide

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Liver Diseases and Hepatic Sinusoidal Cells

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Summary

This chapter reviews current understanding of the regulation of hepatic microcirculation, with particular reference to the authors’ own work on the roles of sinusoidal endothelial cells and the mechanism of dynamic changes in the sinusoidal endothelial fenestrae (SEF) induced by the potent vasoconstrictor endothelin (ET)-l. From the viewpoint of myogenic control in microcirculation, it is considered essential for the local control of hepatic sinusoidal blood flow that the dynamic contracting and relaxing changes of the SEF correspond with those of Ito cells (hepatic stallate cells, HSCs), both of which are mediated by the sinusoidal endothelium-derived vasoconstrictor endothelins (ETs) and the vasodilator nitric oxide (NO). The contractility of the SEF and HSCs entirely depends on the intracellular Ca2+-calmodulin-actomyosin system, in which plasma membrane Ca2+-pump ATPase controlling the intracytoplasmic free calcium concentration [Ca2+]; is one of the key modulators.

ET-1 produced and released from the sinusoidal endothelial cells acts on the HSCs via the ETA receptors as a paracrine effect, inducing a contraction of the HSCs. ET-1 also acts on the sinusoidal endothelial cells themselves via the ETB receptors as an autocrine effect, inducing a contraction of the SEF with a prompt elevation of [Ca2+]j enhanced by a decrease in fenestral plasma membrane Ca2+-pump ATPase. This elevation of [Ca2+]i is markedly suppressed by pretreatment with an ETB receptor antagonist. In parallel with this process, NO produced by NO synthase (NOS) within the sinusoidal endothelial cells gets into the HSCs, inducing a relaxation of the HSCs.

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Authors and Affiliations

  1. Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-0016, Japan

    Masaya Oda & Yoshitaka Kamegaya

  2. Division of Internal Medicine, Kitasato Institute Medical Center Hospital, 6-100 Arai, Kitamoto, Saitama, 364-0026, Japan

    Hiroaki Yokomori

Authors
  1. Masaya Oda
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  2. Hiroaki Yokomori
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  3. Yoshitaka Kamegaya
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Editor information

Editors and Affiliations

  1. Kurume University School of Medicine, Japan

    Kyuichi Tanikawa M.D. (Professor Emeritus, President) (Professor Emeritus, President)

  2. International Institute for Liver Research, Kurume Research Center, 2432-3 Aikawa-machi, Kurume, Fukuoka, 839-0861, Japan

    Kyuichi Tanikawa M.D. (Professor Emeritus, President) (Professor Emeritus, President)

  3. The Second Department of Internal Medicine, Japan

    Takato Ueno M.D. (Assistant Professor, Division Chief) (Assistant Professor, Division Chief)

  4. Liver Cancer Research Division Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan

    Takato Ueno M.D. (Assistant Professor, Division Chief) (Assistant Professor, Division Chief)

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© 1999 Springer-Verlag Tokyo

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Oda, M., Yokomori, H., Kamegaya, Y. (1999). Roles of Sinusoidal Endothelial Cells in the Local Regulation of Hepatic Sinusoidal Blood Flow—Involvement of Endothelins and Nitric Oxide. In: Tanikawa, K., Ueno, T. (eds) Liver Diseases and Hepatic Sinusoidal Cells. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67935-6_11

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  • DOI: https://doi.org/10.1007/978-4-431-67935-6_11

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68012-3

  • Online ISBN: 978-4-431-67935-6

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