© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Endothelin and cardiac arrhythmias: do endothelin antagonists have a therapeutic potential as antiarrhythmic drugs?
rat Duru*Division of Cardiology, University Hospital of Zurich and Cardiovascular Research Laboratory, Institute of Physiology, University of Zurich, Zurich, Switzerland
* Corresponding author. Address for correspondence: Cardiac Arrhythmia Unit, University Hospital of Zurich, Raemistrasse 100, Zurich, 8091, Switzerland. Tel.: 41-1-255-1111; fax: +41-1-255-4597 firat.duru{at}dim.usz.ch
Endothelin-1 (ET-1), the predominant isoform of the ET peptide family and a potent vasoconstrictor, has been shown to aggravate ischemia-induced ventricular arrhythmias. However, there is also evidence that ET-1 may have a direct arrhythmogenic action that is not solely attributable to myocardial ischemia. Proposed mechanisms for the arrhythmogenic effects of ET-1 are prolongation or increased dispersion of monophasic action potential duration, QT prolongation, development of early afterdepolarizations, acidosis, and augmentation of cellular injury. As for an ionic basis for the observed electrophysiologic effects, ET-induced Ca2+ release from intracellular stores, generation of inositol triphosphate, inhibition of delayed rectifier K+ current, and stimulation of the Na+/H+ exchanger may be involved. Recently, some studies have shown that ET receptor antagonists, which promise to be powerful tools in cardiovascular medicine, may also demonstrate antiarrhythmic properties. This review describes the current state of knowledge on the interactions between the ET system and cardiac arrhythmias, and discusses the therapeutic potential of ET antagonists as antiarrhythmic drugs.
KEYWORDS Antiarrhythmic agents; Arrhythmia (mechanisms); Endothelins
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Proven, H. L. Roderick, S. J. Conway, M. J. Berridge, J. K. Horton, S. J. Capper, and M. D. Bootman Inositol 1,4,5-trisphosphate supports the arrhythmogenic action of endothelin-1 on ventricular cardiac myocytes J. Cell Sci., August 15, 2006; 119(16): 3363 - 3375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. G. Baltogiannis, D. G. Tsalikakis, A. C. Mitsi, K. E. Hatzistergos, D. Elaiopoulos, D. I. Fotiadis, Z. S. Kyriakides, and T. M. Kolettis Endothelin receptor-A blockade decreases ventricular arrhythmias after myocardial infarction in rats Cardiovasc Res, September 1, 2005; 67(4): 647 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shimoni and X.-F. Liu Sex differences in the modulation of K+ currents in diabetic rat cardiac myocytes J. Physiol., July 15, 2003; 550(2): 401 - 412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shimoni and X.-F. Liu Role of PKC in autocrine regulation of rat ventricular K+ currents by angiotensin and endothelin Am J Physiol Heart Circ Physiol, April 1, 2003; 284 (4): H1168 - H1181. [Abstract] [Full Text] [PDF]
|
|