Cyclooxygenase 2 and the kidney.
Cyclooxygenase metabolizes arachidonic acid to a family of bioactive fatty acids designated prostaglandins. Two isoforms of cyclooxygenase exist, designated COX1 and COX2. These isoforms are expressed in distinct but important areas of the kidney. COX1 predominates in vascular smooth muscle and collecting ducts, whereas COX2 predominates in the macula densa and nearby cells in the cortical thick ascending limb. COX2 is also highly expressed in medullary interstitial cells. Whereas COX1 expression does not exhibit dynamic regulation, COX2 expression is subject to regulation by several environmental conditions, including salt intake, water intake, medullary tonicity, growth factors, cytokines, and adrenal steroids. Recently, COX2-selective non-steroidal anti-inflammatory drugs have become widely available. Many of the renal effects of non-selective non-steroidal anti-inflammatory drugs (including sodium retention, decreased glomerular filtration rate, and effects on renin-angiotensin levels) appear to be mediated by the inhibition of COX2 rather than COX1. Therefore, in contrast to the gastrointestinal-sparing effects of COX2-selective non-steroidal anti-inflammatory drugs, when considering the kidney, the same caution must be applied when using COX2-selective inhibitors as has been used with traditional non-selective non-steroidal anti-inflammatory drugs.
Breyer
M D
MD
Department of Medicine, Veterans Administration Medical Center and Vanderbilt University, Nashville, Tennessee, USA. matthew.breyer@mcmail.vanderbilt.edu
Harris
R C
RC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000037:antagonists & inhibitors; D051546:Cyclooxygenase 2; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D007668:Kidney / Q000502:physiology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases