An update on cyclooxygenase-2 expression and metabolites in the kidney.
OBJECTIVE
This review highlights recent studies examining the expression and function of cyclooxygenase-2 and its metabolites in the kidney.


RESULTS
Expression of cyclooxygenase-2 is regulated by both physiologic and pathophysiologic perturbations, with volume depletion upregulating macula-densa expression and volume expansion upregulating medullary expression. Macula densa cyclooxygenase-2 is a modulator of juxtaglomerular renin expression, and there is increasing evidence that cyclooxygenase-2 expression is modulated by multiple components of the renin-angiotensin system, including angiotensin II, through both AT1 and AT2 receptors. There are also indications that macula densa cyclooxygenase-2 expression may be regulated by the prorenin/renin receptor. Medullary cyclooxygenase-2 metabolites modulate salt and water excretion, and cyclooxygenase-2 inhibitors lead to sodium and volume retention and may raise blood pressure. There is also increasing evidence that cyclooxygenase-2 expression increases in progressive renal injury. Given their cardiovascular and renal side effects, cyclooxygenase-2 inhibitors are not a feasible intervention for long-term therapy against progressive renal damage, but further delineation of the downstream receptors and synthases involved may provide therapeutic targets.


CONCLUSIONS
Recent studies have highlighted the important role that cyclooxygenase-2 metabolites play both in regulation of normal renal function and as potential mediators of acute and chronic renal injury.
Harris
Raymond C
RC
Department of Medicine, Vanderbilt University, Nashville, and Nashville Veterans Affairs Hospital, Tennessee 37232, USA. ray.harris@vanderbilt.edu
D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D007674:Kidney Diseases / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D012084:Renin-Angiotensin System
D009569:Nitric Oxide; D051546:Cyclooxygenase 2; D004298:Dopamine