Nitric Oxide and Superoxide Significantly Affect Medullary Oxygenation and Urinary Output

Abstract

The goal of this study was to investigate the reciprocal interactions among oxygen (O2), nitric oxide (NO), and superoxide (O2‐), and their effects on medullary oxygenation and urinary output. To accomplish that goal, we developed a detailed mathematical model of solute transport in the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension (PO2) and NO and O2‐ concentration in the outer medulla and upper inner medulla. Due to the nonlinear interactions among O2, NO, and O2‐, the effects of NO and O2‐ on sodium transport, osmolality, and medullary oxygenation cannot be gleaned by considering each solute's effect in isolation. Model simulations further suggest that a sufficiently large reduction in the efficiency of oxygen utilization for tubular transport may be the key contributing factor – more so than oxidative stress – to hypertension‐induced medullary hypoxia. This research was supported in part by NIH grant DK‐89066.