doi:10.1155/2012/789071 Review Article Endothelin-1 and Norepinephrine Overflow from Cardiac

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. 1