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(Hypertension. 2004;43:525.)
© 2004 American Heart Association, Inc.

Brief Review

Cyclooxygenases, the Kidney, and Hypertension

From Division of Nephrology, Departments of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn.

Correspondence to Dr R.C. Harris, Division of Nephrology, S 3322 MCN, Vanderbilt University School of Medicine, Nashville, TN 37232-2372. E-mail Ray.Harris{at}vanderbilt.edu

Selective cyclooxygenase (COX)-2 inhibitors that are in widespread clinical use were developed to avoid side effects of conventional NSAIDs, including gastrointestinal and renal toxicity. However, COX-2 is constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in maintenance of renal blood flow, mediation of renin release, and regulation of sodium excretion. COX-2 inhibition may transiently decrease urine sodium excretion in some subjects and induce mild to moderate elevation of blood pressure. Furthermore, in conditions of relative intravascular volume depletion and/or renal hypoperfusion, interference with COX-2 activity can have deleterious effects on maintenance of renal blood flow and glomerular filtration rate. In addition to physiological regulation of COX-2 expression in the kidney, increased renal cortical COX-2 expression is seen in experimental models associated with altered renal hemodynamics and progressive renal injury (decreased renal mass, poorly controlled diabetes), and long-term treatment with selective COX-2 inhibitors ameliorates functional and structural renal damage in these conditions.

Key Words: COX-2 • COX-1 • hypertension • renin • sodium • glomerular filtration rate • kidney

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