The therapeutic strategy to block ET-1 activities has evolved in the clinic, mainly for PAH, by using orally active small molecule antagonists, targeting selectively ETAR or both ETAR and ETBR. Besides the small molecules, other chemical compounds have been developed to target ET-1R, including monoclonal antibody antagonists and selective peptide agonists and antagonists (51). Here, EDNRA is linked to pulmonary arterial hypertension.