Interactions between COX-2 and the renin-angiotensin system in the kidney.
In adult mammalian kidney, COX-2 expression is found in a restricted subpopulation of cells. The two sites of renal COX-2 localization detected in all species to date are the macula densa (MD) and associated cortical thick ascending limb cells (cTALH) and medullary interstitial cells. Physiological regulation of COX-2 in these cellular compartments suggests functional roles for eicosanoid products of the enzyme. In the MD region, COX-2 expression increases in high renin states [salt restriction, angiotensin converting enzyme (ACE) inhibition, renovascular hypertension], and selective COX-2 inhibitors significantly decrease plasma renin levels and renal renin activity and mRNA expression. An important role for COX-2-derived prostanoids in regulation of renin expression and secretion has also been determined by using mice with selective genetic deletion of either the COX-1 or COX-2 gene. There is evidence for negative regulation of MD/cTALH COX-2 by angiotensin II and by glucocorticoids and mineralocorticoids, suggesting that in the kidney, cortical COX-2 expression is regulated in part by alterations in activity of the renin-angiotensin system.
Harris
R C
RC
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
D000315:Adrenalectomy; D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D051546:Cyclooxygenase 2; D004039:Diet, Sodium-Restricted; D017353:Gene Deletion; D005938:Glucocorticoids / Q000502:physiology; D007527:Isoenzymes / Q000032:analysis / Q000502:physiology*; D007668:Kidney / Q000502:physiology*; D007672:Kidney Cortex / Q000502:physiology; D007679:Kidney Medulla / Q000502:physiology; D051379:Mice; D008901:Mineralocorticoids / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012083:Renin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D005938:Glucocorticoids; D007527:Isoenzymes; D008901:Mineralocorticoids; D012333:RNA, Messenger; D000804:Angiotensin II; D002216:Captopril; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin