Over the past decade our investigative efforts have been directed towards a detailed analysis and understanding of the complex morphologic features, physiologic mechanisms and metabolic processes which are involved in the recovery from acute renal failure. Our investigations have demontrated that the infusion of ATP MgCl2 after an ischemic, toxic or obstructive injury will significantly accelerate the recovery of glomerular and tubular function as well as preserve sublethally injured tubular epithelial cells. The administration of thyroxin to animals, with either toxic or ischemic acute renal failure similarly produces a significant improvement in renal fucntion. Using NMR spectroscopy in vivo, we have demonstrated that the post-ischemic infusion of ATP-MgCl2 and AMP-MgCl2 provides precursors for the resynthesis of cellular ATP. We now propose to determine the cellular and molecular basis of the morphologic and physiologic preservation which accompanies the recovery from acute renal failure and will use the beneficial effect of ATP-MgCl2 and T4 as probes to magnify and enhance the natural process of repair after acute renal injury. We specifically propose to investigate the roles of adenine nucleotide metabolism in the initiation and recovery from acute renal failure with in vivo NMR spectroscopy combined with studies of adenine nucleotide metabolism of proximal tubules from control, ischemic and treated animals, in vitro. We further propose to investigate the integrity of cell plasma membrane function and how it is affected by ischemia and treatment with the ameliorative agent by examining water permeability, sodium permeability and sodium potassium ATPase activity. Finally, we will evaluate the role of calcium in the recovery from acute renal failure to determine whether the influx of calcium after an acute renal insult provides a cross link between the alterations in cellular nucleotides and the loss of membrane integrity.
| Van Why, S K; Mann, A S; Ardito, T et al. (1994) Expression and molecular regulation of Na(+)-K(+)-ATPase after renal ischemia. Am J Physiol 267:F75-85 |
| Gaudio, K M; Thulin, G; Ardito, T et al. (1994) Immature renal tubules are resistant to prolonged anoxia. Pediatr Res 35:152-6 |
| Van Why, S K; Hildebrandt, F; Ardito, T et al. (1992) Induction and intracellular localization of HSP-72 after renal ischemia. Am J Physiol 263:F769-75 |
