Modulation of kinin outflow from isolated perfused rat hearts by endothelin-1

Bradykinin has previously been shown to suppress ET-1 secretion by endothelial cells. In the present study, rat isolated hearts have been perfused with Krebs solution using the Langendorff method. Immunoreactive bradykinin (IRBK) was measured in the perfusate and the basal level was found to be constant for up to 3 h. Ten min perfusions of the hearts with ET-1 at concentrations of 0.2-20 pM produced a dose-related suppression of kinin outflow by over 90% (P < 0.05). At these concentrations ET-1 had no detectable effect on the coronary vasculature or ECG. At 200 pM ET-1 and above, the hearts showed arrhythmias of increasing severity, accompanied at the highest doses by marked coronary constriction and an increase in IRBK outflow.