Submitted on April 15, 2008
Revised on June 20, 2008
Accepted on July 11, 2008
Increased Dietary NaCl induces Renal Medullary PGE2 Production and Natriuresis via the EP2 Receptor
Jian Chen, Min Zhao, Wenjuan He, Ginger L Milne, Jocelyn R.H. Howard, Jason Morrow1, Richard L. Hebert2, Richard M. Breyer1, Jing Chen, and Chuan-Ming Hao1*
1 Vanderbilt University
2 University of Ottawa
* To whom correspondence should be addressed. E-mail: chuanming.hao{at}vanderbilt.edu.
High NaCl diet induces renal medullary COX2 expression and selective intra-medullary infusion of a COX2 inhibitor increases blood pressure in rats on high salt diet. The present study characterized the specific prostanoid contributing to the anti-hypertensive effect of COX2. C57BL/6j mice placed on high NaCl diet exhibited increased medullary COX2 and mPGES1 expression as determined by immunoblot and real-time PCR. cPGES and PGIS were not induced by high salt diet. Immunofluorescence showed mPGES1 in collecting ducts and interstitial cells. High salt increased renal medullary PGE2 as determined by GC/MS. The effect of direct intramedullary PGE2 infusion was examined in anesthetized uninephrectomized mice. Intra-medullary PGE2 infusion (10ng/hr) increased urine volume (from 3.3±0.6 µl/min to 9.5±1.6µl/min) and urine sodium excretion (0.11±0.02 to 0.32±0.05 µEq/min). To determine which 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±0.05µEq/min). The natriuretic effect of intramedullary PGE2 or butaprost was abolished in EP2 deficient mice which exhibit NaCl dependent hypertension. In conclusion, high salt diet increases renal medullary COX2, 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.
