EDN1 and pulmonary arterial hypertension: Even though downregulation of ET-1 by laminar flow has vasoprotective effects and the suppression of ET-1-dependent mechanisms by Nrf2 activators may be efficacious in the treatment of pulmonary arterial hypertension (PAH) [33, 55], suppression of local ET-1 production in the microcirculation may lead to increased endothelial permeability.