Renal concentration defect following nonoliguric acute renal failure in the rat.

The mechanism of impaired renal concentrating ability following nonoliguric ischemic acute renal failure was studied in the rat. Fifty min of complete occlusion of the renal artery and vein with contralateral nephrectomy resulted in reversible, nonoliguric acute renal failure. Eight days following induction of acute renal failure, a defect in 30 hr dehydration urine osmolality was present when experimental animals were compared with uninephrectomized controls (1,425 +/- 166 versus 2,267 +/- 127 mOsm/kg water respectively, P less than 0.001). Comparable postdehydration plasma vasopressin levels in experimental and control animals and an impaired hydro-osmotic response to exogenous vasopressin in experimental animals documented a nephrogenic origin of the defect in urine concentration. Lower urinary excretion of prostaglandin E2 in experimental animals and a failure of cyclo-oxygenase inhibition with 10 mg/kg of indomethacin to improve dehydration urine osmolality suggested that prostaglandin E2 antagonism of vasopressin action did not contribute to the concentration defect. Postdehydration inner medullary (papillary) interstitial tonicity was significantly reduced in experimental animals versus controls (870 +/- 85 versus 1,499 +/- 87 mOsm/kg water respectively, P less than 0.001). To determine if this decreased interstitial tonicity was due to vascular mechanisms, papillary plasma flow was measured and found to be equivalent in experimental and control animals. To examine a role for biochemical factors in the renal concentration defect, cyclic nucleotide levels were measured in cytosol and membrane fragments. A decrease in vasopressin and sodium fluoride-stimulated adenylate cyclase was found in outer medullary tissue of experimental animals. In contrast, vasopressin-stimulated adenylate cyclase activity was comparable in the inner medullary tissue of control and experimental animals. Our study suggests a defect in generation of renal inner medullary interstitial solute as a mechanism of the impaired urinary concentration observed in this model of acute renal failure.