title: Critical role of exogenous nitric oxide in ROCK activity in vascular smooth muscle cells.
abstract: OBJECTIVE
  Rho-associated kinase (ROCK) signaling pathway has been shown to mediate various cellular functions including cell proliferation, migration, adhesion, apoptosis, and contraction, all of which may be involved in pathogenesis of atherosclerosis. Endogenous nitric oxide (NO) is well known to have an anti-atherosclerotic effect, whereas the exogenous NO-mediated cardiovascular effect still remains controversial. The purpose of this study was to evaluate the effect of exogenous NO on ROCK activity in vascular smooth muscle cells (VSMCs) in vitro and in vivo.
  
  
  METHODS
  VSMCs migration was evaluated using a modified Boyden chamber assay. ROCK activities were measured by Western blot analysis in murine and human VSMCs and aorta of mice treated with or without angiotensin II (Ang II) and/or sodium nitroprusside (SNP), an NO donor.
  
  
  RESULTS
  Co-treatment with SNP inhibited the Ang II-induced cell migration and increases in ROCK activity in murine and human VSMCs. Similarly, the increased ROCK activity 2 weeks after Ang II infusion in the mouse aorta was substantially inhibited by subcutaneous injection of SNP.
  
  
  CONCLUSIONS
  These findings suggest that administration of exogenous NO can inhibit ROCK activity in VSMCs in vitro and in vivo.
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Maruhashi
authors.affiliation: Department of Regeneration and Medicine, Research Center for Radiation Genome Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, Hiroshima, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Akimichi
authors.initials: A
authors.lastname: Iwamoto
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Oda
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kajikawa
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hidaka
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kihara
authors.affiliation: Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: Department of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Nakashima
authors.affiliation: Department of Integrated Rehabilitation, Hiroshima International University, Hiroshima, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Goto
authors.affiliation: Section of Cardiology, University of Chicago Medical Center, Chicago, IL, United States of America.
authors.forename: James K
authors.initials: JK
authors.lastname: Liao
authors.affiliation: Department of Regeneration and Medicine, Research Center for Radiation Genome Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, Hiroshima, Japan; Department of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000804:Angiotensin II; D009599:Nitroprusside; D009569:Nitric Oxide; D054460:rho-Associated Kinases