This overview provides information on the pathophysiology of the inducible nitric oxide synthase/nitric oxide (iNOS/NO) system in the injury to cultured renal tubular epithelia, freshly isolated proximal tubules, and the whole organ after hypoxic or ischemic insult. The findings emphasize the role of concomitant oxidative and nitrosative stress and the role of peroxynitrite in the ensuing renal dysfunction. Scavenging peroxynitrite using seleno-organic compounds like ebselen provides renoprotection against ischemic injury. These sequelae of renal ischemia are a result of endothelial dysfunction, which is most probably responsible for the "no-reflow" phenomenon and further aggravation of tubular ischemia during the early reperfusion period. Recent studies have demonstrated that transplantation of functional endothelial cells into ischemic kidney provided a dramatic renoprotective effect. In conclusion, the intricate relations between endothelial and epithelial cells, based in part on the relations between endothelial and inducible nitric oxide synthases, are perturbed in renal ischemia primarily as a result of endothelial dysfunction precipitating epithelial injury.