Skip Navigation


Cardiovascular Research Advance Access originally published online on December 22, 2008
Cardiovascular Research 2009 81(4):780-787; doi:10.1093/cvr/cvn356
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
81/4/780    most recent
cvn356v2
cvn356v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Osanai, T.
Right arrow Articles by Okumura, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Osanai, T.
Right arrow Articles by Okumura, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Coupling factor 6 enhances Src-mediated responsiveness to angiotensin II in resistance arterioles and cells

Tomohiro Osanai1,*, Hirofumi Tomita1, Motoi Kushibiki1, Masahiro Yamada1, Makoto Tanaka1, Toshihiro Ashitate1, Takashi Echizen1, Chisato Katoh1, Koji Magota2 and Ken Okumura1

1 Department of Cardiology, Hirosaki University Graduate School of Medicine, 5 Zaifu-Cho, Hirosaki 036-8562, Japan
2 Asubio Pharma Co., Ltd, Biomedical Center, Biopharma Research Department, Biotechnology Group, 2716-1, Kurakake, Akaiwa, Chiyoda-machi, Ohra-gun, Gunma-ken 370-0503, Japan

* Corresponding author. Tel: +81 172 39 5057; fax: +81 172 35 9190. E-mail address: osanait{at}cc.hirosaki-u.ac.jp

Aims: Coupling factor 6 (CF6) induces hypertension by attenuating the endothelial generation of prostacyclin. However, intracellular signalling of CF6 in the resistance arteriole vascular smooth muscle cells (VSMCs) that are directly related to vasoconstriction has not been determined. Here we investigated the direct effect of exogenous CF6 on Ca2+ signalling in cultured VSMCs and the in vivo role of endogenous CF6 in the genesis of hypertension using CF6 transgenic (TG) mice.

Methods and results: CF6 induced a monophasic increase in the intracellular free Ca2+ concentration ([Ca2+]i) through nifedipine-sensitive Ca2+ channels in A7r5 cells, a cell line of VSMCs, and enhanced the angiotensin II-induced spike phase of [Ca2+]i to a greater degree in VSMCs derived from spontaneously hypertensive rats (SHRs). In the mesenteric arterioles obtained from CF6-TG mice that manifested hypertension, angiotensin II-induced vasoconstriction was enhanced, compared with wild-type mice, and its enhancement was abolished by an anti-CF6 antibody. Pre-treatment with PP1, a tyrosine kinase c-Src inhibitor, blocked CF6-induced increase in Ca2+ signalling in VSMCs and vasoconstriction in TG mice. The receptor of CF6 was F1 motor of adenosine triphosphate (ATP) synthase with a higher affinity in SHRs. CF6 decreased intracellular pH via activation of ATPase activity and led to c-Src activation to a greater degree in SHR-derived VSMCs.

Conclusion: CF6 causes hypertension by directly enhancing Ca2+ signalling in VSMCs and vasoconstriction in the mesenteric arteriolar network via c-Src activation.

KEYWORDS Arachidonic acids; Microcirculation; Peptide; Prostacyclin; Spontaneously hypertensive rats; Vascular resistance

Time for primary review: 40 days


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.