Intra-renal oxygenation in rat kidneys during water loading: Effects of cyclooxygenase (COX) inhibition and nitric oxide (NO) donation

Purpose: To evaluate intra-renal oxygenation by blood oxygenation level dependent (BOLD) MRI in rat kidneys during water loading and to investigate if the NO donating moiety in naproxcinod could compensate for the effect of cyclooxygenase (COX) inhibition of naproxen. Materials and Methods: Nineteen male Sprague Dawley rats were divided into three groups and dosed with vehicle, naproxen or naproxcinod by gavage for two weeks. On the day of the experiment, hypotonic saline with glucose was infused intravenously to induce water diuresis. BOLD MRI data to monitor renal oxygenation and timed urine samples for estimation of prostaglandins (PGs) and urine flow were obtained. Results: The data in this study is consistent with previous experience in humans in that pre-treatment with naproxen abolished the improvement in medullary oxygenation during water loading. In addition, the inhibition of PGs by naproxcinod reached similar levels as naproxen but maintained the improvement in oxygenation in renal medulla during water loading. Conclusion: This suggests that naproxcinod may have less nephrotoxicity and that the NO donating moiety partially compensates for the hemodynamic effects of prostaglandin inhibition by naproxen.