In this regard, ET-1 limitation of flow with exercise is enhanced in skeletal muscle with hypertension, hypercholesterolemia, type 2 diabetes and aging (Hearon and Dinenno, 2016; Table 2) and in the lung in pulmonary hypertension secondary to myocardial infarction (Houweling et al., 2006; Merkus et al., 2007), while the ET-1 limitation of flow is reduced in heart with myocardial infarction (Merkus et al., 2005; de Beer et al., 2011b). This evidence concerns the gene EDN1 and pulmonary arterial hypertension.