Abstract: SA-PO1087

PGE2 EP1 Receptors Contribute to Hypertensive Injury in Mouse Kidney

Session Information

Category: Hypertension

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

Authors

  • Ghossein, Jamie, University of Ottawa, Ottawa, Ontario, Canada
  • Nasrallah, Rania, University of Ottawa, Ottawa, Ontario, Canada
  • Gutsol, Alex, University of Ottawa, Ottawa, Ontario, Canada
  • Hebert, Richard L., University of Ottawa, Ottawa, Ontario, Canada
Background

Prostaglandin E2 (PGE2) derived from COX-2 is upregulated in hypertension and diabetes, and we previously reported that the PGE2 EP1 receptor is involved in glomerular injury and proteinuria in the diabetic mouse. We hypothesize that EP1 contributes to renal injury in hypertension.

Methods

Using a genetic model of hypertension, where TTRhRen mice overexpress renin (Htn), we studied the effects of EP1 deletion using 4 mouse groups at 24 weeks of age: wildtype (WT), EP1-/-, Htn, and HtnEP1-/-. All male mice were placed in metabolic cages, and 24 hour urine was collected. Urine osmolality was determined by freezing point depression and albumin levels were measured by ELISA. Glomerular filtration rate was determined by FITC-Inulin clearance, and systolic blood pressure was measured by tail-cuff plethysmography. Kidneys were fixed and PAS stained for pathological analysis of glomerular, mesangial, and capillary areas using ImageJ photo analysis software.

Results

Urine osmolality was decreased by 33% in Htn mice compared to WT mice, and further decreased by 17% in HtnEP1-/- mice compared to Htn mice. Urine albumin was elevated by 10 fold in Htn mice compared to WT mice, and further increased in HtnEP1-/- mice by 2.5 fold compared to Htn mice. Blood pressures were elevated by 25mmHg in Htn mice compared to WT mice, but this hypertensive state was unaffected by EP1 deletion. FITC-inulin clearance was unchanged in Htn mice, but reduced by 50% in HtnEP1-/- mice compared to WT. Pathological analysis revealed that mesangial cell numbers were unchanged in Htn mice, but stimulated 1.5 fold in both groups lacking EP1 receptors compared to WT. Glomerular and mesangial volume were increased by 1.25 fold and 1.5 fold in Htn mice compared to WT respectively, and mesangial volume was significantly higher in HtnEP1-/- mice compared to Htn mice, reaching 1.95 fold of WT. In contrast, capillary volumes were unchanged in Htn mice, but significantly reduced by 50% in EP1-/- and HtnEP1-/- mice compared to WT mice.

Conclusion

Taken together, the data suggest that the EP1 receptor maintains glomerular permeability and prevents hypertension induced glomerular injury, independent of effects on blood pressure.

Funding

  • Government Support - Non-U.S.