EDN1 and hypertensive disorder: Several mechanisms have been proposed based on the preclinical and clinical studies, including; (1) increased total peripheral resistance induced by endothelial dysfunction due to predominantly the reduced production of vasodilators (NO and PGI2), the increased production of vasoconstrictors (ET-1) and the reduced nitric oxide bioavailability, (2) increase in vascular tone, (3) vascular rarefaction, (4) and renal thrombotic microangiopathy, leading to proteinuria and hypertension, (5) natriuresis and impaired lymphatic function could also contribute to development of hypertension (21).