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...