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Abstract: PO1818

Empagliflozin Prevents Impaired Sensitivity of Afferent Neurons with Renal Axons During a High-Salt Diet

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Rodionova, Kristina, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Ditting, Tilmann, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Germany
  • Wopperer, Laura, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Hilgers, Karl F., Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Linz, Peter, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Cordasic, Nada, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Ott, Christian, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Germany
  • Schiffer, Mario, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Schmieder, Roland E., Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Amann, Kerstin U., Universitätsklinikum Erlangen, Abteilung für Nephropathologie, Erlangen, Germany
  • Veelken, Roland, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Germany
Background

Afferent renal nerve pathways likely play a role in salt sensitive hypertension. We recently reported that high salt diet (HS) impairs these afferent renal pathways in rats. Now we tested the hypothesis that during HS a decrease in sensitivity of renal afferent neurons is prevented by the SGLT2 inhibitor empagiflozin.

Methods

Respective groups of rats were put on HS containing 8% NaCl or a normal diet. Two groups (HS, controls) received empagiflozin 20 mg/kg BW/day orally. Renal neurons were retrogradely labeled with DiI. In culture, labeled dorsal root ganglion neurons (DRG Th11-L2) with renal afferents were investigated electrophysiologically using current clamp mode to assess action potential generation during current injection (neurons were characterized as tonic highly active (> 5 action potentials, AP) and phasic less active neurons (5 AP upon stimulation).

Results

In neurons from rats on HS, the relation of tonic highly active neurons to less active phasic neurons shifted consistently towards phasic units (63,8% tonic neurons in controls vs. 42%* on HS, *p<0.05, z-test). However, continuous treatment with empagiflozin preserved the proportion of tonic neurons as in controls (67,9% on HS with concomitant administration of empagiflocin). In controls, empagiflozin did not affect the proportion of tonic to phasic neurons (63,8% tonic neurons in controls vs. 67,9% on HS & empagliflozin, p=0.7, z-test). Blood pressure and heart rate were not altered by HS and or treatment with any chosen dose of empagiflozin.

Conclusion

In rats, chronically elevated sodium intake (8% NaCl) reduced the sensitivity and stimulability of renal afferent DRG neurons. Under these circumstances, concomitant treatment with the SGLT2 inhibitor empagiflozin preserved the function of renal afferent DRG neurons. SGLT 2 inhibitors may help to treat dysfunction of renal innervation in cardiovascular disease.