Mast cell degranulation – a mechanism for the anti‐arrhythmic effect of endothelin‐1?

Background and purpose:  The aim of this study was to investigate whether the previously reported anti‐arrhythmic effect of endothelin‐1 (ET‐1) is mediated by degranulation of cardiac mast cells prior to myocardial ischaemia. Experimental approach:  Male Sprague‐Dawley rats received either ET‐1 (1.6 nmol·kg −1 ) in the presence or absence of disodium cromoglycate (DSCG; 20 mg·kg −1 ·h −1 ) prior to coronary artery occlusion (CAO). In separate experiments rats were given compound 48/80 (50 µg·kg −1 ) to compare the effects of ET‐1 with those of a known mast cell degranulator. Ischaemia‐induced ventricular arrhythmias were detected through continuous monitoring of a lead I electrocardiogram. After 30 min of CAO, the hearts were removed and mast cell degranulation determined by histological analysis. A parallel series of sham groups were performed to determine the direct effects of ET‐1 and compound 48/80 on mast cell degranulation in the absence of ischaemia. Key results:  ET‐1 and compound 48/80 both exerted profound anti‐arrhythmic effects, significantly reducing the total number of ventricular ectopic beats ( P < 0.001) and the incidence of ventricular fibrillation ( P < 0.05). These anti‐arrhythmic effects were abolished by concomitant DSCG infusion prior to CAO. In sham animals ET‐1 and compound 48/80 both induced mast cell degranulation ( P < 0.001), an effect which was abolished by DSCG, confirming their ability to induce degranulation of mast cells. Conclusions and implications:  These results demonstrate for the first time that when given prior to ischaemia ET‐1 mediates its anti‐arrhythmic effects, at least in part, via cardiac mast cell degranulation.