EDN1 and endothelial dysfunction: Studies involving CMD patients have revealed a number of underlying pathophysiological mechanisms, including endothelial dysfunction, reduced coronary flow reserve (CFR), and autonomic imbalance.7 Specifically, an imbalance between the endothelium-derived vasodilator nitric oxide (NO) and the vasoconstrictor endothelin-1 (ET-1) is a proposed mechanism for CMD.10