Effect of specific and non-specific inhibition of COX-2 on renal oxygenation before and after water diuresis.
OBJECTIVE
Water diuresis usually increases medullary oxygenation as a result of increased medullary synthesis of prostaglandins, but it is not clear whether this involves activation of cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2).


METHODS
The effects of celecoxib, a selective inhibitor of COX-2, and of ibuprofen, a non-specific inhibitor of COX-1 and COX-2, upon renal oxygenation during water diuresis were studied in a double-blind, prospective manner in 13 young women (age 24-34 years) using blood-oxygen level dependent magnetic resonance imaging. Celecoxib 200 mg b.i.d. for 4 days was compared with ibuprofen 80 mg b.i.d. for 4 days and with a placebo.


RESULTS
There was no effect of either drug on urinary volume, urinary osmolal concentration, or creatinine clearance. Water diuresis alone elicited a significant increase in oxygenation in borderline areas between cortex and medulla, which was eliminated by celecoxib or ibuprofen.


CONCLUSIONS
Renal medullary oxygenation is improved by water diuresis in normal young women in a way that is blocked by a selective inhibitor of COX-2 as well as non-selective cyclooxygenase inhibitors. Selective COX-2 may be expected to have significant effects on renal functions.
Gilbert
Scott
S
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Zuo
Chun
C
Epstein
Franklin H
FH
D000328:Adult; D001834:Body Water / Q000378:metabolism*; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D004231:Diuresis / Q000187:drug effects / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*
D052246:Cyclooxygenase 2 Inhibitors; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib; D010100:Oxygen