EDN1 and ischemia: In our recent study using isolated perfused rat hearts, however, exogenous big ET-1 (0.1, 0.3 and 1 nM) did not increase NE overflow induced by 40-min global myocardial ischemia as opposed to the case of exogenously applied ET-1, in spite of the fact that ET-1 levels in coronary effluent from the heart exposed to protracted ischemia were dose-dependently increased by exogenous big ET-1 application [41].