Endothelin and the ischaemic heart

Wainwright, C.L., McCabe, C. and Kane, K.A. (2005) Endothelin and the ischaemic heart. Current Vascular Pharmacology, 3(4), pp. 333-341.

Abstract

Soon after its identification as a powerful vasoconstrictor peptide, endothelin (ET-1) was implicated as a detrimental agent involved in determining the outcome of myocardial ischaemia and reperfusion. Early experimental studies demonstrated that ETA selective and mixed ETA/ETB receptor antagonists can reduce infarct size and prevent ischaemiainduced ventricular arrhythmias in models of ischaemia/reperfusion, implying that ET-1 acts through the ETA receptor to contribute to injury and arrhythmogenesis. However, as our understanding of the physiology of ET-1 has expanded, the role of ET-1 in the ischaemic heart appears ever more complex. Recent evidence suggests that ET-1 exerts actions on the heart that are not only detrimental (vasoconstriction, inhibition of NO production, activation of inflammatory cells), but which may also contribute to tissue repair, such as inhibition of cardiomyocyte apoptosis. In addition, ET-1-induced mast cell degranulation has been linked to a homeostatic mechanism that controls endogenous ET-1 levels, which may have important implications for the ischaemic heart. Furthermore the mechanism by which ET-1 promotes arrhythmogenesis remains controversial. Some studies imply a direct electrophysiological effect of ET-1, via ETA receptors, to increase monophasic action potential duration (MAPD) and induce early after-depolarisations (EADs), while other studies support the view that coronary constriction resulting in ischaemia is the basis for the generation of arrhythmias. Moreover, ET-1 can induce cardioprotection (precondition) against infarct size and ventricular arrhythmias, through as yet incompletely understood mechanisms. To enable us to identify the most appropriate means of targeting this system in a therapeutically meaningful way we need to continue to explore the physiology of ET-1, both in the normal and the ischaemic heart.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McCabe, Dr Chris
• Authors: Wainwright, C.L., McCabe, C., and Kane, K.A.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Current Vascular Pharmacology
• Publisher: Bentham Science Publishers
• ISSN: 1570-1611
• Copyright Holders: Copyright © 2005 Bentham Science Publishers
• First Published: First published in Current Vascular Pharmacology 3(4):333-341
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher