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Abstract: PO1092

The Effect of Epidermal Growth Factor Inhibition on Distal Nephron Sodium Reabsorption in Mice

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

  • 901 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • King, Keyona N., Emory University School of Medicine, Atlanta, Georgia, United States
  • Hoover, Robert S., Tulane University School of Medicine, New Orleans, Louisiana, United States
Background

Studies have shown that the epidermal growth factor (EGF) decreases the activity of ENaC while the influence of EGF on renal Na+ transport via NCC is unknown. Previous investigations in mDCT-15 cells showed that EGF increases endocytosis of NCC. Using radio-telemetry, we found that EGF inhibition increases systolic blood pressure in response to increasing the dietary Na+ intake. Our results in consolidation with other researchers, suggest that EGF affects BP by influencing the activity of ENaC and NCC. Our goal is to determine whether EGF inhibition increases BP via alterations in Na+ reabsorption.

Methods

Using metabolic cages, we collected urine samples at three time points over 24 hours in 7 week old male mice. Normal salt (LS) diet (0.4% Na chow) was given for baseline collections and high salt (HS) diet (4% Na chow) for experimental collections. Only the experimental (E) group, n=4 received gefitinib (an EGF receptor tyrosine kinase inhibitor) orally at 100 mg/kg/d and the control (C) group, n=4 received placebo. Hydrochlorothiazide (HCTZ) 2.4mg per 10g BW orally and amiloride 1.45 µg/g via IP injection were administered. Following a washout period, HCTZ and amiloride were given simultaneously to assess the total effect on NCC and ENaC.

Results

There was no difference in the average urinary Na+ excretion over 24 hours for baseline measurements between the groups when receiving the LS diet (experimental (E) group: 105 ± 13 mmol vs. control (C) group: 82 ± 23 mmol, N.S.).However, when giving the HS diet and HCTZ, the E group had a higher average urinary Na+ excretion over 24 hours in response to a higher dietary Na+ intake (E group: 966 ± 108 vs. C group: 517 ± 139 mmHg, p<0.05). For amiloride with HS diet there was no difference in average urinary Na+ excretion between the groups (E group: 1130 ± 127 vs. C group: 920 ± 48 mmol, N.S.).When giving both HCTZ and amiloride to the mice while receiving the HS diet, the E group had a higher urinary Na+ excretion compared to the C group (E group: 997 ± 66 vs. C group: 777 ± 48 mmol, p<0.05).

Conclusion

Therefore, our data suggests that inhibition of EGF increases Na+ reabsorption via NCC. As previously suggested, this may indicate that EGFR ligands act as tonic inhibitors of NCC tubular sodium reabsorption. Future experiments will explore the in vivo effects of EGFR inhibition on sodium excretion along other components of the nephron.

Funding

  • NIDDK Support