EDN1 and endothelial dysfunction: To maintain vascular homeostasis, there is a fine balance between vasodilator (NO) and vasoconstrictor agents (e.g., endothelin-1 (ET-1)) (Cardillo et al., 2000; Versari et al., 2009); and although the pathophysiological mechanisms leading to endothelial dysfunction are likely multifactorial, a hallmark of endothelial dysfunction in the aging vasculature was shown to be reduced bioavailability of NO and enhanced reactivity of ET-1 (Boss and Seegmiller, 1981; Toda, 2012; Xu et al., 2017; Dong et al., 2019).