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


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.


CONCLUSIONS
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.
Ji
Lin
L
Department of Radiology, NorthShore University HealthSystem, Evanston, Illinois, USA.
Li
Lu-Ping
LP
Schnitzer
Thomas
T
Du
Hongyan
H
Prasad
Pottumarthi V
PV
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D000860:Hypoxia; D007668:Kidney / Q000473:pathology*; D008297:Male; D009288:Naproxen / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000737:chemistry*; D020030:Nitric Oxide Donors / Q000737:chemistry*; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry*; D011453:Prostaglandins / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D020030:Nitric Oxide Donors; D011453:Prostaglandins; C111751:naproxen-n-butyl nitrate; D014867:Water; D009569:Nitric Oxide; D009288:Naproxen; D011451:Prostaglandin-Endoperoxide Synthases