The endothelin system is upregulated in animal models of OSA and likely is upregulated with OSA in humans, although plasma ET-1 levels might not be increased.1,3,9,16,38,112,127,165–168 Intermittent hypoxia increased ET-1 in cerebral vessels of mice by ≍2 orders of magnitude and increased mRNA for endothelin-converting enzyme-1 and endothelin receptor type A but not mRNA for endothelin receptor type B.112 Furthermore, the increase in ET-1 expression occurred in both the endothelium and vascular smooth muscle. This evidence concerns the gene EDN1 and obstructive sleep apnea syndrome.