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(Hypertension. 2005;45:178.)
© 2005 American Heart Association, Inc.

Editorial Commentaries

Are All COX-2 Inhibitors Created Equal?

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

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

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Prostaglandins (PGs) are biologically active lipids derived from the cyclooxygenase (COX)-mediated metabolism of arachidonic acid. They are constitutively produced in certain tissues (eg, brain, gut, and kidney), and their synthesis is increased at sites of inflammation. Prostanoids function as important mediators of inflammation and modulate a variety of physiological processes, including maintenance of gastric mucosal integrity, renal hemodynamic regulation, renin synthesis and release, and tubular reabsorption of salt and water.¹ Cyclooxygenase, or PG synthase G₂/H₂, is the rate-limiting enzyme responsible for the initial conversion of arachidonic acid to PGG₂ and subsequently to PGH₂. PGH₂ is then metabolized by tissue-specific isomerases to produce prostaglandins and thromboxanes.

There are 2 distinct isoforms of cyclooxygenase, COX-1 and COX-2, which share 66% homology in amino acid sequence^2–4 but have different patterns of expression and regulation. COX-1, traditionally termed the "constitutive" enzyme, is widely distributed in tissues, and its level of activity is not dynamically regulated. COX-2, the glucocorticoid-sensitive "inducible" enzyme, is more restricted in its basal expression and is upregulated in response to inflammation, resulting in increased prostanoid production at the site of inflammation.

NSAIDs, which block both isoforms COX-1 and COX-2, have been widely used in the treatment of inflammatory conditions. However, the adverse effects of NSAIDs, especially gastrointestinal toxicity, have limited their long-term use in clinical settings. The hypothesis that NSAID-induced gastrointestinal toxicity was related to the inhibition of gastric COX-1, whereas the anti-inflammatory properties caused by COX-2 inhibition⁵ led to the development of the new anti-inflammatory agents, the . . . [Full Text of this Article]

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