Skip to main content
Article thumbnail
Location of Repository

Endothelin and the ischaemic heart

By C.L. Wainwright, C. McCabe and K.A. Kane

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

Topics: R1
Publisher: Bentham Science Publishers
Year: 2005
OAI identifier: oai:eprints.gla.ac.uk:16851
Provided by: Enlighten

Suggested articles

Citations

  1. (2001). A et al. Ventricular arrhythmias induced by endothelin-1 or by acute ischaemia: a comparative analysis using threedimensional mapping. Cardiovasc Res
  2. (2004). Activators of PPARgamma antagonize protection of cardiac myocytes by endothelin-1. Biochem Biophys Res Commun
  3. (2000). Antiadrenergic Effects doi
  4. (2001). Antiarrhythmic and electrophysiological effects of the endotheline receptor antagonists,
  5. (1996). Apoptosis in ischaemic and reperfused rat myocardium. Circ Res doi
  6. (1996). Arrhythmogenic action of endothelin peptides in isolated perfused whole hearts from guinea pig and rats. Pharmacology doi
  7. (1998). Arrhythmogenic effects induced by coronary conversion of pulmonary big endothelin to endothelin: aggravation of this phenomenon in heritable hyperlipidaemia. doi
  8. (1998). Attenuation of ischaemia/reperfusion injury in rats by a caspase inhibitor. Circulation doi
  9. (1995). Beneficial effects of the endothelin receptor antagonist bosentan on myocardial and endothelial injury following ischaemia/reperfusion in the rat. doi
  10. (1990). Biology of disease: new insights into “The riddle of the mast cells”: microenvironmental regulation of mast cell development and phenotypic heterogeneity. Lab Invest doi
  11. (2001). Calcineurin pathway is required for endothelin-1-mediated protection against oxidant stress-induced apoptosis in cardiac myocytes. Circ Res doi
  12. (2003). Cardiac myofibroblasts isolated from the site of myocardial infarction express endothelin de novo.
  13. (2000). Cardioprotection from ischaemia and reperfusion injury by an endothelin A-receptor antagonist in relation to nitric oxide production. doi
  14. (1991). Contribution of endogenous endothelin to the extension of myocardial infarct size in rats. Circ Res doi
  15. (1999). Coronary vascular endothelium-myocyte interactions in protection of the heart by ischaemic preconditioning.
  16. (1997). Differential effects of endothelin-1 on basal and isoprenaline-enhanced Ca2+ current in guinea-pig ventricular myocytes. doi
  17. (1993). Effect of endothelin-1 on neutrophil adhesion to endothelial cells and perfused heart. Circulation doi
  18. (1995). Effects of endothelin-1 and the ETA-receptor antagonist BQ123, on ischaemic arrhythmias in anaesthetised rats. doi
  19. (2003). Effects of endothelin-1 on mitochondrial function during the protection against myocardial cell apoptosis. doi
  20. (2005). Electrophysiological and haemodynamic effects of endothelin ETA and ETB receptors in normal and ischaemia working rabbit hearts. Br J Pharmac. doi
  21. (1991). Electrophysiological effects of endothelin-1 on canine myocardial cells. doi
  22. (2001). Endothelin and cardiac arrhythmias: do endothelin antagonists have a therapeutic potential as antiarrhythmic drugs? Cardiovasc Res doi
  23. (1998). Endothelin and ischaemic arrhythmias – antiarrhythmic or arrhythmogenic? Cardiovasc Res
  24. (1992). Endothelin enhances delayed potassium current via PLC in guinea pig ventricular myocytes.
  25. (1997). Endothelin in myocardial ischaemia and reperfusion. Cardiovasc Res doi
  26. (2000). Endothelin-1 and photoreleased diacylglycerol increase L-type Ca 2+ current by activation of protein kinase C in rat ventricular myocytes. doi
  27. (2000). Endothelin-1 as a protective factor against beta-adrenergic agonist-induced apoptosis in cardiac myocytes. doi
  28. (1996). Endothelin-1 can reduce infarct size through protein kinase C and KATP channels in the isolated rat heart. Cardiovasc Res doi
  29. (1992). Endothelin-1 enhances calcium entry through T-type calcium channels in cultured neonatal rat ventricular myocytes. Circ Res doi
  30. (1990). Endothelin-1 enhances superoxide generation of human neutrophils stimulated by the chemotactic peptide Nformyl-mthionyl-leucyl-phenylalanine. Biochem Biophys Res Comm doi
  31. (2005). Endothelin-1 exerts a preconditioning-like cardioprotective effect against ischaemia/reperfusion injury via the ETA receptor and the mitochondrial KATP channel in the rat in vivo. doi
  32. Endothelin-1 induces mast cell degranulation and increases tryptase level in the murine myocardium in vitro. J Mol Cell Cardio 2005; Abstract In
  33. (2000). Endothelin-1 induces mucosal mast cell degranulation in then rat small intestine. Life Sci doi
  34. (1997). Endothelin-1 inhibition of cardiac ATP-sensitive K + channels via pertussis-toxin-sensitive G-proteins. Cardiovasc Res doi
  35. (1997). Endothelin-1 inhibits the slow component of cardiac delayed rectifier K + currents via a pertussis toxinsensitive mechanism. Circ Res doi
  36. (2004). Endothelin-1 mediates cardiac mast cell degranulation, matrix metalloproteinase activation and myocardial remodeling in rats. doi
  37. (1996). Endothelin-1 partially inhibits ATP-sensitive K + current in guinea pig ventricular cells. doi
  38. (2002). Endothelin-1 receptor antagonists reduce caqrdiac electrical instability induced by high glucose in rats. Naunyn Schmeidbergs Arch Pharmacol doi
  39. (1995). Endothelin-1-induced reduction of myocardial infarct size by activation of ATP-sensitive potassium channels in a rabbit model of myocardial ischaemia and reperfusion. doi
  40. (2000). Endothelin-A receptor antagonist LU 135.252 inhibits the formation of ventricular arrhythmias caused by intrapericardial infusion of endothelin-1. J Cardiovasc Pharmacol 2000; 36(Suppl 1): doi
  41. (1997). Endothelin-receptor antagonist FR 139317 reduces infarct size when given before, but not after, coronary artery occlusion. doi
  42. (1989). Endothelin: a potent vasoconstrictor associated with vasospasm. Life Sci doi
  43. (1996). Endothelin(A) receptor antagonism by PD 156707 does not reduce infarct size after coronary artery occlusion/reperfusion in pigs.
  44. (1992). Endothelins belong to the assortment of mast cell-derived and mast cell-bound cytokines. New Biol
  45. (1995). ET1 contributes to ischaemiareperfusion injury in isolated rat heart: attenuation of ischaemic-injury by the endothelin-1 antagonists BQ123 and BQ-610. J Mol Cell Cardiol
  46. (2002). Function of the endothelin B receptor in cardiovascular physiology and pathophysiology. Pharmacol Ther
  47. (2003). Increased endothelin-1 and endothelin receptor expression in myocytes of ischaemic and reperfused rat hearts and ventricular myocytes exposed to ischaemic conditions and its inhibition by nitric oxide generation. doi
  48. (1995). Increased in vivo expression and production of endothelin-1 by porcine cardiomyocytes subjected to ischaemia. Circ Res doi
  49. (1998). Increased monophasic action potential dispersion in Endothelin-1 induced ventricular arrhythmias. doi
  50. (1989). Increased plasma concentrations of endothelin-1 and big endothelin-1 in acute myocardial infarction. Lancet doi
  51. (2004). Inositol-1,4,5-trisphosphate-dependent Ca(2+) signalling in cat atrial excitation-contraction coupling and arrhythmias. doi
  52. (2004). Intracellular signalling pathways for norepinephrine- and endothelin-1-mediated regulation of myocardial cell apoptosis. Mol Cell Biochem doi
  53. (1994). Intravenous administration of the endothelin-1 antagonist BQ-123 does not ameliorate myocardial ischaemic injury following acute coronary artery occlusion in the dog. Cardiovasc Res doi
  54. (2000). Investigating the dual nature of endothelin-1: Ischaemia or direct arrhythmogenic effect? Life Sciences doi
  55. (2001). Involvement of nitric oxide in cardioprotective effect of endothelin receptor antagonist during ischaemiareperfusion. doi
  56. (2000). Ischaemic preconditioning in rats: role of mitochondrial K(ATP) channel in preservation of mitochondrial function.
  57. (1990). Ischemia and reperfusion increase 125I-labeled endothelin-1 binding in rat cardiac membranes. doi
  58. (2001). Kortvely A et al. Different effects of endothelin-1 on calcium and potassium currents in canine ventricular cells. doi
  59. (2000). Kortvely A et al. Effects of endothelin-1 on calcium and potassium currents in undiseased human ventricular myocytes. Plugers Arch doi
  60. (1989). Lethal ischaemia due to intracoronary endothelin in pigs.
  61. (1995). Local overflow and enhanced tissue content of endothelin following myocardial ischaemia and reperfusion in the pig: modulation by L-arginine. Cardiovasc Res doi
  62. (2005). Mast cells and endothelin-1: a life saving biological liaison? Trends Immunol doi
  63. (2004). Mast cells promote homeostasis by olimiting endothelin-1-induced toxicity. Nature doi
  64. (2001). NHE1-inhibitor cariporide prevents the transient reperfusion-induced shortening of the monophasic action potential after coronary ischemia in pigs. Basic Res Cardiol doi
  65. (1997). p53 and the hypoxia-induced apoptosis of cultured neonatal rat cardiac myocytes. doi
  66. (1997). Peroxynitrite inhibits leukocyteendothelial cell interactions and protects against ischaemia-reperfusion injury in rats. doi
  67. (2000). Pharmacological analysis by HOE642 and KB-R9032 of the role of Na(+)/H(+) exchange in the endothelin-1-induced Ca(2+) signalling in rabbit ventricular myocytes. doi
  68. (1994). Plasma endothelin determination as a prognostic indicator of 1-year mortality after acute myocardial infarction. Circulation doi
  69. (1991). Plasma endothelin levels during myocardial ischaemia and reperfusion. Life Sci doi
  70. (1994). Potent vasoconstriction mediated by endothelin ETB receptors in canine coronary arteries. Circ Res doi
  71. (1996). Pretreatment with endothelin-1 mimics ischaemic preconditioning against infarction in isolated rabbit heart. doi
  72. (1993). Protection of ischemia-reperfusion injury by sydnonimine donors via inhibition of neutrophil-endothelium interaction. doi
  73. (1996). Protective effect of the specific endothelin-1 antagonist BQ-610 on mechanical function and energy metabolism during ischaemia reperfusion injury in isolated perfused rat hearts. doi
  74. (1995). Protective effects of non-peptide endothelin receptor antagonist bosentan on myocardial ischaemic amnd reperfusion injury in the pig. Cardiovasc Res doi
  75. (1989). Radioimmunoassay for endothelin and immunoreactive endothelin in culture medium of bovine endothelial cells. Biochem Biophys Res Comm doi
  76. (1998). Receptor-Mediated Effects of Endothelin on the L-Type Ca 2+ Current in Ventricular Cardiomyocytes. J Pharmacol Ex. Ther
  77. (1988). Reduction in infarct size by the prostacyclin analogue iloprost (ZK 36374) after experimental coronary artery occlusion-reperfusion. Am Heart J doi
  78. (2001). Regulation by endothelin-1 of Na+-Ca2+ exchange current (I(NaCa)) from guinea-pig isolated ventricular myocytes. Cell Calcium doi
  79. (2004). Regulation of cardiac myocyte apoptosis by the GATA-4 transcription factor. Life Sci doi
  80. (1994). Role of endogenous endothelin in myocardial and coronary endothelial injury after ischaemia and reperfusion in rats: studies with bosentan, a mixed ETA-ETB antagonist. doi
  81. (1994). Role of endothelin during reperfusion after ischaemia in isolated perfused rat heart. doi
  82. (1996). Role of endothelin in a rabbit model of acute myocardial infarction: Effects of receptor antagonists. doi
  83. (1994). Role of endothelin receptor subtype B (ET-B) in myocardial ischaemia. Life Sci doi
  84. (1995). Sakamoto A et al. Negative chronotropic effect of endothelin1 mediated through ETA receptors in guinea pig atria. Circ Res doi
  85. (2004). Sarafotoxin 6c (S6c) reduces infarct size and preserves mRNA for the ETB receptor in the ischaemic/reperfused myocardium of anaesthetised rats. doi
  86. (2000). Sarafotoxin 6c protects against ischaemia induced cardiac arrhythmias in vivo and in vitro in the rat. doi
  87. (1990). Tahara A et al. Circulating immunoreactive endothelin in ischaemic heart disease. doi
  88. (1990). The arrhythmogernic action of endothelin in rats. doi
  89. (2000). The effect of S6c on platelet aggregation and leukocyte free radical generation in rat blood in vitro and ex vivo.
  90. (1990). The effects of diltiazem on the coronary heamodynamics and cardiac functional effects produced by intracoronary administration of endothelin-1 in the anaesthetized dog. doi
  91. (2004). The effects of endothelin-1 on degranulation, cytokine and growth factor production by skin-derived mast cells. doi
  92. (2001). The effects of endothelin-1 on ischaemic-induced ventricular arrhythmias in rat isolated hearts. doi
  93. (1998). The endothelin A receptor antagonist LU 135252 protects the myocardium from neutrophil injury during ischaemia/reperfusion. Cardiovasc Res doi
  94. (1993). The endothelin-1 receptor antagonist BQ123 reduces infarct size in a canine model of coronary occlusion and reperfusion. Cardiovasc Res doi
  95. (2002). The ET(A) receptor antagonist LU 135252 has no electrophysiological or anti arrhythmic effects during myocardial ischaemia/reperfusion in dogs. Clin Sci (Lond)
  96. (1998). The novel non-peptide selective endothelin A receptor antagonist LU 135,252 protects against myocardial ischaemic ajnd reperfusion injury in the pig. Acta Physiol Scand doi
  97. (1989). The possible role of endothelin1 in the pathogenesis of coronary vasospasm. doi
  98. (2000). The role of endothelin, protein kinase C and free radicals in the mechanism of post-ischaemic endothelial dysfunction in guinea pig hearts. doi
  99. (2002). The role of inositol 1,4,5-trisphosphate receptors in Ca(2+) signalling and the generation of arrhythmias in rat atrial myocytes. doi
  100. (2002). Transient isopeptide-specific induction of myocardial endothelin-1 mRNA in congestive heart failure in rats. Basic Res Cardiol
  101. (1993). Use of the endothelin antagonists BQ123 and PD142893 to reveal three endothelin receptors mediating smooth muscle contraction and the release of EDRF. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.