Hypothesis: Endothelin 1 (ET-1) is a potent pulmonary vasoconstrictor and mediator of lung diseases. Antagonism of the ET-1 mediated effects has become an important therapeutic approach. ET-1 (A and B) receptors are differentially distributed in the lung vasculature. While the ETA receptors mainly mediate vasoconstriction, the endothelial ETB receptor seems to have vasodilative properties. We sought if antagonism of ET receptors can be achieved by inhalation of specific blockers in a model of ET-1 mediated pulmonary hypertension (PH). Materials and Methods: The isolated ventilated and buffer perfused rabbit lung was used to establish a model of acute ET-1 induced PH. Two selective ET (A and B) and one dual ET-1 receptor antagonist (ETRA) (Tezosentan) were administered into pulmonary circulation or as an aerosol. Results: During intravascular application, the selective ET-A receptor antagonist BQ-123 and the dual ETRA Tezosentan dose dependently attenuated ET-1 induced PH, whereas the selective ET-B receptor antagonist BQ-788 augmented the ET-1 effects. Equimolar doses of aerosolized BQ-788 did not influence pulmonary vasoconstriction, but the BQ-123 aerosol exerted its specific effects. Antagonising both ET-1 receptors via aerosol induced a greater effect on ET-1 mediated pulmonary vasoconstriction than aerosol administration of a selective ETA receptor antagonist. Conclusions: Antagonizing pulmonary vasoconstriction as an indicator of ET-1 mediated lung disease is possible via aerosolization of a selective ET-A receptor and even stronger by a dual ET-receptor blocker.