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Cardiology Research and Practice
Volume 2012, Article ID 789071, 7 pages
Review Article

Endothelin-1 and Norepinephrine Overflow from Cardiac Sympathetic Nerve Endings in Myocardial Ischemia

1Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka 569-1094, Japan
2Department of Pharmacology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
3Department of Pharmacy, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan

Received 9 April 2012; Revised 14 May 2012; Accepted 15 May 2012

Academic Editor: Theofilos M. Kolettis

Copyright © 2012 Masashi Tawa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


In protracted myocardial ischemia, sympathetic activation with carrier-mediated excessive norepinephrine (NE) release from its nerve endings due to reversal of NE transporter in an outward direction is a prominent cause of arrhythmias and cardiac dysfunction. Endothelin-1 (ET-1) and its receptors are intimately involved in the regulation of this carrier-mediated NE overflow in protracted myocardial ischemia. The ET-1 system is often complex, sometimes involving opposing actions depending on which receptor subtype is activated, which cells are affected, and whether stimuli are endogenously generated or exogenously applied. Therefore, a detailed understanding of the ET-1 system is important for applying drugs acting on this system in clinical settings for the treatment of ischemic cardiac disease. This article provides a detailed analysis of how the ET-1 system is involved in the regulation of carrier-mediated NE release from sympathetic nerve endings in protracted myocardial ischemia.