ARRHYTHMOGENIC ACTION OF ENDOTHELIN PEPTIDES IN ISOLATED-PERFUSED WHOLE HEARTS FROM GUINEA-PIGS AND RATS

The arrhythmogenic actions of endothelin peptides were studied in isol ated perfused hearts from guinea pigs and rats. Digoxin-induced ectopi c ventricular complexes were partially antagonized by phosphoramidon, an endothelin-converting enzyme inhibitor. On the contrary, these rhyt hm disturbances were potentiated by big endothelin-1 in isolated perfu sed whole hearts from guinea pigs. Endothelin-1, when infused through the coronary circulation at a concentration of 10(-10) mol/l, produced an increase in coronary perfusion pressure without altering the heart rate and contractility in the isolated perfused hearts of rats. Howev er, ventricular ectopic complexes occurred when the rise in coronary p erfusion pressure reached the peak value. BQ 485, an endothelin-A rece ptor antagonist, at a concentration of 10(-6) mol/l, completely blocke d the vasoconstrictor and arrhythmogenic effects of endothelin-1. In B Q 485-pretreated rat hearts, endothelin-1 produced a fall in coronary perfusion pressure and a slight positive inotropic response which coul d be blocked by N-G-nitro-L-arginine methyl ester, a nitric oxide synt hase inhibitor. BQ 485 at the same concentration also caused a signifi cant reduction in the duration but not the onset of ventricular ectopi c complexes in the guinea pig isolated perfused heart induced by digox in. These results were taken as evidence of the arrhythmogenic action of endothelin peptides and their possible participation in the ventric ular dysrhythmia induced by digoxin.