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(Hypertension. 2004;44:396.)
© 2004 American Heart Association, Inc.

Editorial Commentaries

Hypertension and Cyclooxygenase-2 Inhibitors

Target: The Renal Medulla

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

Correspondence to Chuan-Ming Hao, S3223 MCN, Div of Nephrology, Department of Medicine, Vanderbilt University Medical School, Nashville, TN 37232. E-mail Chuanming.hao@vanderbilt.edu

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

Cyclooxygenase (COX)-inhibiting NSAIDs are widely prescribed to treat arthritis, exerting analgesic and antiinflammatory effects via their capacity to block endogenous prostaglandin synthesis.^1,2 Unfortunately, their widespread use has been associated with an increased risk of developing hypertension,^3,4 and clinical experience with COX-2 selective inhibitors suggests they similarly predispose hypertension.⁵

The physiological mechanisms through which COX-2 inhibitors increase blood pressure are gradually being elucidated. Experimental evidence from animal models suggests an important vasodilator role for endogenous COX-2–derived prostaglandins, reducing the systemic pressor effects of angiotensin II.⁶ These findings underscore the importance of COX-2 activity in regulating the tone of peripheral resistance vessels. COX-2, but not COX-1, inhibition also reduces renal medullary blood flow and urine salt excretion,⁶ which is in agreement with clinical studies in humans showing COX-2 inhibition impairs renal salt excretion.⁷ As a consequence of COX-2 inhibition, the combined increase in peripheral activity of pressors (like angiotensin II) and reduced renal salt excretion likely conspire to predispose humans to hypertension.

The precise cellular sources of the COX-2–derived products promoting vascular dilator tone and renal salt excretion remain uncharacterized. In the kidney, COX-2 expression is restricted to 2 main cellular compartments: the macula densa with surrounding cortical thick ascending limb⁸ and renal medullary interstitial cells.^9,10 In this issue of Hypertension, Zewde and Mattson provide evidence that focuses attention on the renal medulla as the important intrarenal site of endogenous COX-2 activity protecting against the development of systemic hypertension.¹¹ These investigators report that when animals were placed on a high-salt diet, . . . [Full Text of this Article]

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