Targeting ET-1 signaling as a therapy for metabolic impairments associated with OSA was motivated by numerous studies demonstrating elevated ET-1 plasma levels in humans or animals with type 2 diabetes (34–37, 57), as well as by reports suggesting direct involvement of ET-1 signaling in the pathogenesis of glucose intolerance and hyperglycemia (18, 38, 40–49). This evidence concerns the gene EDN1 and type 2 diabetes mellitus.