Mechanisms for Enhanced Endothelium-Derived Hyperpolarizing Factor-Mediated Responses in Microvessels in Mice

• Ohashi Junko

  Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine

• Sawada Ayuko

  Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine

• Nakajima Sota

  Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine

• Noda Kazuki

  Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine

• Takaki Aya

  Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine

• Shimokawa Hiroaki

  Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine

抄録

Background: Endothelium-derived relaxing factors play an important role in cardiovascular homeostasis. Among them, endothelium-derived hyperpolarizing factor (EDHF) is important especially in microcirculation. It has previously been demonstrated that endothelium-derived hydrogen peroxide (H₂O₂) is an EDHF in animals and humans and that endothelial nitric oxide synthase (eNOS) plays diverse roles as a nitric oxide (NO) generating system in conduit arteries and as an EDHF/H₂O₂ generating system in microvessels. As compared with NO-mediated responses, those by EDHF are resistant to atherosclerosis, contributing to the maintenance of cardiovascular homeostasis. The aim of this study is to elucidate the molecular mechanisms for enhanced EDHF-mediated responses in microvessels. Methods and Results: This study used male wild-type mice and caveolin-1-deficient mice (caveolin-1^-/- mice). In the endothelium, eNOS was functionally suppressed in mesenteric arteries (microvessels) compared with the aorta (conduit arteries), for which Ca²⁺/calmodulin-dependent protein kinase kinase β (CaMKKβ) and caveolin-1 are involved, as EDHF-mediated responses were inhibited by STO-609 (an inhibitor of CaMKKβ) and in caveolin-1^-/- mice, respectively. In vascular smooth muscle, relaxation responses to H₂O₂ were enhanced through a protein kinase G1α (PKG1α)-mediated mechanism in mesenteric arteries compared with the aorta, as they were inhibited by Rp-8-Br-cGMPS (an inhibitor of PKG1α). Conclusions: These results indicate that CaMKKβ, caveolin-1, and PKG1α are substantially involved in the mechanisms for the enhanced EDHF-mediated responses in microvessels in mice.  (Circ J 2012; 76: 1768–1779)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 76 (7), 1768-1779, 2012

  一般社団法人 日本循環器学会

キーワード

• Endothelial nitric oxide synthase
• Endothelium-derived hyperpolarizing factor
• Microveesels
• Nitric oxide

詳細情報

• CRID: 1390282680080243456
• NII論文ID: 10030503147
• NII論文ID: 10030503846
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-12-0197
• COI: 1:CAS:528:DC%2BC38XhtFOktr3F
• ISSN: 13474820
• ISSN: 13469843
• ISSN: http://id.crossref.org/issn/13469843
• PubMed: 22466633
• Web Site: https://www.jstage.jst.go.jp/article/circj/76/7/76_CJ-12-0197/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2013201286
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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