title: Increased dietary NaCl induces renal medullary PGE2 production and natriuresis via the EP2 receptor.
abstract: 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 PGE(2) as determined by gas chromatography/negative ion chemical ionization mass spectrometry. The effect of direct intramedullary PGE(2) infusion was examined in anesthetized uninephrectomized mice. Intramedullary PGE(2) infusion (10 ng/h) increased urine volume (from 3.3 +/- 0.6 to 9.5 +/- 1.6 mul/min) and urine sodium excretion (0.11 +/- 0.02 to 0.32 +/- 0.05 mueq/min). To determine which E-prostanoid (EP) receptor(s) mediated PGE(2)- dependent natriuresis, EP-selective prostanoids were infused. The EP(2) agonist butaprost produced natriuresis (from 0.06 +/- 0.02 to 0.32 +/- 0.05 mueq/min). The natriuretic effect of intramedullary PGE(2) 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 PGE(2) synthesis. Renal medullary PGE(2) promotes renal sodium excretion via the EP2 receptor, thereby maintaining normotension in the setting of high salt intake.
authors.affiliation: Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Wenjuan
authors.initials: W
authors.lastname: He
authors.forename: Ginger L
authors.initials: GL
authors.lastname: Milne
authors.forename: Jocelyn R H
authors.initials: JR
authors.lastname: Howard
authors.forename: Jason
authors.initials: J
authors.lastname: Morrow
authors.forename: Richard L
authors.initials: RL
authors.lastname: Hébert
authors.forename: Richard M
authors.initials: RM
authors.lastname: Breyer
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Chuan-Ming
authors.initials: CM
authors.lastname: Hao
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis*; D007679:Kidney Medulla / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009318:Natriuresis; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D012964:Sodium / Q000652:urine*; D017673:Sodium Chloride, Dietary / Q000378:metabolism*
chemical_list: C545645:Ptger2 protein, mouse; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D017673:Sodium Chloride, Dietary; D012964:Sodium; D015232:Dinoprostone