MODULATION OF KININ OUTFLOW FROM ISOLATED-PERFUSED RAT HEARTS BY ENDOTHELIN-1

Bradykinin has previously been shown to suppress ET-1 secretion by end othelial cells. In the present study, rat isolated hearts have been pe rfused with Krebs solution using the Langendorff method. Immunoreactiv e 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 hear ts with ET-1 at concentrations of 0.2-20 pM produced a dose-related su ppression of kinin outflow by over 90% (P < 0.05). At these concentrat ions ET-1 had no detectable effect on the coronary vasculature or EGG. At 200 pM ET-1 and above, the hearts showed arrhythmias of increasing severity, accompanied at the highest doses by marked coronary constri ction and an increase in TREK outflow.