Positive chronotropic effects of endothelin, a novel endothelium-derived vasoconstrictor peptide

Endothelin (ET) is a novel 21-amino-acid peptide isolated from the culture supernatant of porcine aortic endothelial cells, which has a potent vasoconstricting effect. It has been suggested that ET increases Ca2+ influx via a voltage-dependent Ca2+ channel. The purpose of the present study is to investigate the mode of actions of ET on the cardiac automaticity. ET increased the sinoatrial nodal rate in a dose-dependent manner on the isolated right atria of guinea pigs. The positive chronotropic effect of ET was very potent and the ED50 value was 0.4 nM. These results suggest that ET is one of the most potent cardio-acceleratory substances.