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Abstract: TH-PO511

Role for Collecting-Duct ET-1 in the Response to High-Salt Diet plus Mineralocorticoid Treatment

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic

Authors

  • Gumz, Michelle L., University of Florida, Gainesville, Florida, United States
  • Douma, Lauren G., University of Florida, Gainesville, Florida, United States
  • Lynch, I. Jeanette, University of Florida, Gainesville, Florida, United States
  • Cheng, Kit-yan, University of Florida, Gainesville, Florida, United States
  • Holzworth, Meaghan R., University of Florida, Gainesville, Florida, United States
  • Barral, Dominique H., University of Florida, Gainesville, Florida, United States
  • Masten, Sarah H., University of Florida, Gainesville, Florida, United States
  • Wingo, Charles S., University of Florida, Gainesville, Florida, United States
Background

Mice lacking the circadian clock protein Per1 exhibit a reduced night:day ratio in urinary Na excretion during the acute response to a high salt (HS, 4% NaCl) diet plus mineralocorticoid (DOCP) treatment. New results indicate that 24 hr urinary Endothelin-1 (ET-1) peptide is increased in male kidney-specific Per1 KO mice compared to control mice under these conditions. ET-1 is a known circadian clock target gene. These data led us to hypothesize that ET-1 action is important for maintaining the normal night:day ratio in renal Na excretion in response to HS/DOCP.

Methods

We generated renal collecting duct-specific ET-1 KO mice using Aqp2-Cre. Male CD ET-1 KO (n=5) mice and age-matched littermate controls (WT)(n=6) were acclimated to metabolic cages. Urine collections (24 hr) were made over 3 days of control diet and 3 days of HS. Mice were then treated with 75 µg/g BW DOCP. Urine collections (12 hr) were made for 3 days of HS/DOCP. Cumulative Na balance was calculated. Genotype effects were assessed during the HS and HS/DOCP interval using linear regression. Genotype and treatment effects were assessed by 2-way repeated measured ANOVA. Night:day urine Na excretion ratios were compared by t-test.

Results

Contrary to our hypothesis, CD-specific KO of ET-1 did not alter the night:day ratio in urine Na excretion in response to HS/DOCP (KO 5.6±1.4 , WT 3.8±0.7 , p=>0.05). The rate of increase in cumulative Na balance was significantly greater in CD ET-1 KO mice vs. WT.

Conclusion

Under the conditions tested, CD ET-1 does not appear to be necessary to maintain night:day differences in urinary Na handling. However, consistent with the known natriuretic role for ET-1 in the CD, CD ET-1 mice do retain significantly more Na in response to HS/DOCP compared to WT. These data demonstrate that CD ET-1 is necessary for the natriuretic response to a high salt diet plus mineralocorticoid.