Most evidence indicates that ETBR is the main receptor responsible for the natriuretic actions of ET-1 in the nephron; however, observations in mice with double ETAR/ETBR knockout in the collecting duct, which display more severe hypertension than ETBR knockout mice, indicate that ETAR contributes to ET-1–induced natriuresis (reviewed by Kohan et al. [33]). Here, EDN1 is linked to hypertensive disorder.