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1 Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA
2 Department of Medicine, Vanderbilt University, Nashville, TN, USA
* To whom correspondence should be addressed. E-mail: ray.harris{at}vanderbilt.edu.
Cyclooxygenase-2 (COX-2) is involved in kidney morphogenesis and is transiently elevated in the immature kidney. In adult rats, renal cortical COX-2 expression is tonically suppressed by mineralocorticoids (MC) and glucocorticoids (GC), and induced by chronic salt restriction. Young rats have low levels of GC and are in a state of relative volume depletion. The present study was designed to investigate the mechanisms underlying elevated cortical COX-2 expression in immature kidney. Supplementation of GC or MC suppressed cortical COX-2 expression in suckling rats. GC suppression was significantly, but not completely prevented by either an MC receptor antagonist or a GC receptor antagonist. MC suppression was completely prevented by an MR antagonist. Salt supplementation suppressed cortical COX-2 expression in a dose- and time-dependent pattern in the suckling rats. Cortical COX-2 expression in the weanling rats was up-regulated by low-salt diet and down-regulated by high-salt diet. These results suggest that relative volume depletion and reduced GC levels are involved in elevated cortical COX-2 expression in the immature rodent kidney.
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