Regulation of renal cortical cyclooxygenase-2 in young rats.
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 the 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 a mineralocorticoid receptor 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 upregulated by a low-salt diet and downregulated by a 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.
Zhang
Ming-Zhi
MZ
George O'Brien Center for Kidney and Urological Diseases, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Wang
Su-wan
SW
Cheng
Huifang
H
Zhang
Yahua
Y
McKanna
James A
JA
Harris
Raymond C
RC
D000375:Aging / Q000378:metabolism; D000450:Aldosterone / Q000097:blood; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D000833:Animals, Suckling / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology; D051546:Cyclooxygenase 2; D003900:Desoxycorticosterone / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D014886:Weaning
D007527:Isoenzymes; D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone; D000450:Aldosterone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D003345:Corticosterone