Kidney Week

Abstract: SA-PO1020

Contribution of Collecting Duct NOS1 in the Regulation of Urine Flow in Hydrated and Dehydrated States

Session Information

• Fluid and Electrolytes: Basic - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Hyndman, Kelly A., University of Alabama at Birmingham, Birmingham, Alabama, United States

Kelly A. Hyndman,

• Mendoza, Luciano D., University of Alabama at Birmingham, Birmingham, Alabama, United States

Luciano D. Mendoza,

Background

We previously determined that collecting duct (CD) nitric oxide synthase-1 (NOS1) was critical for maintaining fluid-electrolyte balance during high Na⁺ intake. Mice with genetic deletion of all NOS1 splice variants from the principal cells of the CD (CDNOS1KO), have reduced urine flow after a single high Na⁺ meal compared to control mice even though food and water intake was similar. This suggests that CD NOS1 may regulate CD water permeability during high Na⁺ challenges. The purpose of this study was to determine if CD NOS1 is a regulator of water permeability during chronic hydration or water deprivation.

Methods

Male and female (n=6 per sex/genotype/treatment) CDNOS1KO and littermate NOS1^flox/flox(control) mice were randomly assigned to the hydration or 24 h dehydration protocols. All mice were placed on 5% sucrose water to encourage hydration. After 3 days, half of the mice were switched to water deprivation. Urine was collected diurnally matching the 12 h light schedule of the room.

Results

In male mice, both genotypes drank similar amounts while hydrated, and produced similar amounts of urine. With water deprivation, CDNOS1KO male mice produced significantly more urine than controls during their active period (182±0.04 vs 40±0.03 μl/12 h, p = 0.02), and urine from CDNOS1KO male mice was very concentrated (UOsm= 4632±193 mOsm/kg H₂O). Plasma osmolality rose similarly in both control (300±3 vs 315±2 mOsm/kg H₂O ) and CDNOS1KO (301±2 vs 314±3 mOsm/kg, P_genotype=0.53 P_hydration<0.01, P_gxh= 0.3) during dehydration. In the females, fluid intake was significantly reduced in the CDNOS1KO mice during their active period compared to controls (7.2±1.6 vs 15.2±2.6 ml/day, p=0.01), and likewise there was a reduction in urine volume (3.1±1.2 vs 8.2±2.0 ml/day, p= 0.03). With dehydration, female control and CDNOS1KO mice both produced very little urine and concentrated urine (125±0.05 and 105±0.04 μl/12h, p = 0.99). Plasma osmolality following dehydration was increased in the controls (from 300±3 to 308±2 mOsm/kg H₂O) and further exacerbated in CDNOS1KO (from 309±4 to 319±6 mOsm/kg, P_genotype=0.02 P_hydration= 0.03, P_gxh= 0.8).

Conclusion

In conclusion, CD NOS1 does contribute to the urine concentrating mechanisms of the kidney in both sexes, although it is a minor component. Interestingly, CD NOS1 is crucial in female mice to properly regulate plasma osmolality.

Funding

• NIDDK Support