Vasodilator action of endothelin-1 in the perfused rat heart

The effects of bolus injections of porcine endothelin (ET-1, 1-100 pmol) on the coronary microvasculature of isolated perfused rat heart were examined. Results show that ET-1 possesses dose-dependent vasodilator as well as vasoconstrictor properties. The vasodilator effect was transient and preceded its more pronounced and persistent vasoconstrictor action. ET-1-induced vasodilation in rat heart was not associated with release of prostacyclin (PGI2), as shown by radioimmunoassay (RIA) analysis of cardiac effluent and was not blocked by the cyclooxygenase inhibitors flurbiprofen (2 microM) or BW755c (7.5 microM). Neither was the dilatory response to ET-1 inhibited by haemoglobin (10 microM) or potentiated by superoxide dismutase (20 U/ml) but it was abolished by methylene blue (20 microM). However, methylene blue itself caused coronary dilation which could mask the vasodilator action of ET-1. These results show that in isolated perfused rat heart ET-1 possesses a vasodilator action that is not mediated by PGI2 and that may also be independent of release of endothelium-derived relaxing factor (EDRF).