Abstract: SA-PO1088

PGE2 EP1 Receptor Regulates Renal Aquaporin and Sodium Transporter Expression and Inhibits AVP-Dependent Water Reabsorption and Sodium Transport in Mouse Collecting Duct

Session Information

Category: Hypertension

  • 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

Authors

  • Nasrallah, Rania, Kidney Research Centre, Ottawa, Ontario, Canada
  • Zimpelmann, Joe A., Kidney Research Centre, Ottawa, Ontario, Canada
  • Ghossein, Jamie, Kidney Research Centre, Ottawa, Ontario, Canada
  • Kennedy, Chris R., Kidney Research Centre, Ottawa, Ontario, Canada
  • Burns, Kevin D., The Ottawa Hospital - Riverside Campus, Ottawa, Ontario, Canada
  • Hebert, Richard L., Kidney Research Centre, Ottawa, Ontario, Canada
Background

Prostaglandin E2 (PGE2) regulates glomerular hemodynamics, renin secretion, and tubular transport. The purpose of this study was to determine the contribution of PGE2 EP1 receptors to salt and water homeostasis, given that we previously reported no effect on blood pressure in mice lacking EP1.

Methods

Male FVB EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate kidney aquaporins, sodium transporters, and transport function at 8 wks of age in 4 groups: wild-type (WT), EP1-/-, Htn, HtnEP1-/-. Total RNA was isolated from renal cortex and medulla, and microdissected proximal tubules (PT), thick ascending limb (TAL), and cortical (CCD) and inner medullary collecting ducts (IMCD) for quantitative PCR analysis. CCD and IMCD were microdissected for in vitro perfusions to determine tubular fluid reabsorption in response to PGE2 and vasopressin (AVP), and transepithelial voltage in CCD stimulated with PGE2. CCD were also pre-treated with amiloride (ENaC inhibitor) or hydrochlorothiazide (pendrin inhibitor) prior to PGE2 stimulation.

Results

Cyclooxygenase (COX)-1 and microsomal PGE2 synthase mRNA were increased and COX2 was decreased in mice lacking EP1, along with increases in EP3 and reductions in EP2 and EP4 mRNA throughout the nephron. PT sglt1, NHE3, and AQP1 were increased in HtnEP1-/-, but sglt2 was increased in EP1-/- mice. TAL NKCC2 was reduced in the cortex but increased in the medulla. IMCD AQP1 and ENaC were increased, but AVP V2 receptor and urea transporter-1 were reduced in all mouse groups compared to WT. In WT and Htn mice, PGE2 inhibited AVP-stimulated water transport in the IMCD, but not in EP1-/- or HtnEP1-/- mice. Similarly, PGE2 depolarized the transepithelial voltage (inhibited sodium transport) in mouse CCD via EP1 in WT and Htn mice, but not in in mice lacking EP1; both amiloride and hydrochlorothiazide attenuated the inhibitory response of PGE2.

Conclusion

Taken together, the data suggest that EP1 regulates renal aquaporins and sodium transporters, and EP1 plays a major role in attenuating AVP-mediated water transport and inhibiting sodium transport in the mouse collecting duct. The inhibition of sodium transport in response to PGE2 is mediated by both ENaC and pendrin-dependent pathways.

Funding

  • Government Support - Non-U.S.