EDN1 and Hypertension: Severe and rapidly progressive hypertension damages the endothelial lining of small blood vessels,24 leading to the stimulated release of vasoconstrictive substances and RAAS activation.25 In response to the cascade of events, increased renin production yields higher levels of angiotensin II, a powerful vasoconstrictor that stimulates endothelin-1 production and promotes inflammation, oxidative stress, and fibrosis.26 This rapid activation process creates a self-perpetuating cycle that exacerbates kidney and vascular lesions in other organs.