Electrophysiological and haemodynamic effects of endothelin ETA and ETB receptors in normal and ischaemic working rabbit hearts

1 The aims of this study were to determine if endothelin-1 (ET-1) under normal and ischaemic conditions exhibits a direct arrhythmogenic effect that is independent of its ability to cause coronary vasoconstriction, and to determine the contribution of the ETA and ETB receptor subtype. 2 ETA/B (with ET-1) and ETA (ET-1 in the presence of BQ-788) receptor activation resulted in a significant reduction in both epi- and endocardial monophasic action potential duration (MAPD(90)). ETA receptor activation reduced both epi- and endocardial effective refractory period (ERP). This MAPD90 and ERP shortening were associated with a reduction in coronary flow, myocardial contractility and induction of ventricular fibrillation (VF) during ERP measurement. 3 The ETB agonist sarafotoxin (S6c) had no marked, or concentration-dependent, effect on MAPD90, ERP, myocardial contractility or induction of arrhythmias. 4 Neither ET-1 nor S6c, given prior to coronary artery occlusion, significantly changed the ischaemia-induced dispersion of MAPD90, ERP or the % incidence of VF. 5 In conclusion, neither ETA nor ETB receptor stimulation has a direct arrhythmogenic effect in isolated rabbit hearts under normal or ischaemic conditions. The ET-1-induced arrhythmogenic effect observed in nonischaemic hearts is likely to be the result of the associated coronary vasoconstriction caused by ETA receptor stimulation resulting in myocardial ischaemia.