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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/F818    most recent 90253.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chen, J. Articles by Hao, C.-M. Search for Related Content PubMed PubMed Citation Articles by Chen, J. Articles by Hao, C.-M.

Increased dietary NaCl induces renal medullary PGE₂ production and natriuresis via the EP2 receptor

Divisions of ¹Nephrology and ²Clinical Pharmacology, Department of Medicine, Vanderbilt University, and ³Veterans Affairs Medical Center, Nashville, Tennessee; ⁴DongFang Hospital, Fujian; ⁵Department of Cellular and Molecular Medicine, Kidney Research Centre, University of Ottawa, Ontario, Canada; and ⁶Huashan Hospital, Shanghai, China

Submitted 16 April 2008 ; accepted in final form 11 July 2008

A high-NaCl diet induces renal medullary cyclooxygenase (COX)2 expression, and selective intramedullary infusion of a COX2 inhibitor increases blood pressure in rats on a high-salt diet. The present study characterized the specific prostanoid contributing to the antihypertensive effect of COX2. C57BL/6J mice placed on a high-NaCl diet exhibited increased medullary COX2 and microsomal prostaglandin E synthase1 (mPGES1) expression as determined by immunoblot and real-time PCR. Cytosolic prostaglandin E synthase and prostacyclin synthase were not induced by the high-salt diet. Immunofluorescence showed mPGES1 in collecting ducts and interstitial cells. High salt increased renal medullary PGE₂ as determined by gas chromatography/negative ion chemical ionization mass spectrometry. The effect of direct intramedullary PGE₂ infusion was examined in anesthetized uninephrectomized mice. Intramedullary PGE₂ infusion (10 ng/h) increased urine volume (from 3.3 ± 0.6 to 9.5 ± 1.6 µl/min) and urine sodium excretion (0.11 ± 0.02 to 0.32 ± 0.05 µeq/min). To determine which E-prostanoid (EP) receptor(s) mediated PGE₂- dependent natriuresis, EP-selective prostanoids were infused. The EP₂ agonist butaprost produced natriuresis (from 0.06 ± 0.02 to 0.32 ± 0.05 µeq/min). The natriuretic effect of intramedullary PGE₂ or butaprost was abolished in EP2-deficient mice, which exhibit NaCl-dependent hypertension. In conclusion, a high-salt diet increases renal medullary COX2 and mPGES1 expression, and increases renal medullary PGE₂ synthesis. Renal medullary PGE₂ promotes renal sodium excretion via the EP2 receptor, thereby maintaining normotension in the setting of high salt intake.

cyclooxygenase 2; prostaglandin E synthase; hypertension