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The discovery of a potent vasoconstrictor, endothelin (ET)-1, derived from vascular endothelial cells was among a variety of key lines of investigation that helped to fuel a major explosion of studies related to endothelial cell biology. This was particularly evident within the pharmaceutical industry where receptor antagonists were quickly developed and are now on the market for treatment of pulmonary hypertension and in development for other diseases such as diabetic nephropathy and cancer. Importantly, we know that the kidney contains the highest level of ET-1 production and receptor expression in the body where it has been demonstrated to function as a pro-natriuretic autocrine and paracrine factor that is activated in conditions of high salt intake. This eBook provides a review of the various mechanisms whereby ET-1 has been shown to function within the kidney through a wide range of actions that include direct effects on tubular transport, intrarenal hemodynamics, as well as neural and endocrine functions. Much has yet to be discerned, but it is clear that the ET system is a major physiological regulator of fluid-electrolyte balance and blood pressure through these renal actions.