Kidney Week

Abstract: TH-OR73

Increased Blood Pressure in Mice with Impaired Function of Afferent Renal Nerves Due to Lack of Sodium Nav1.8 Channels

Session Information

• Hypertension and CVD: Research Advances
  October 24, 2024 | Location: Room 5, Convention Center
  Abstract Time: 04:30 PM - 04:40 PM

Category: Hypertension and CVD

• 1601 Hypertension and CVD: Basic

Authors

• Rodionova, Kristina, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany

Kristina Rodionova, MD

• Hutter, Eva, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany

Eva Hutter, MSc

• Ditting, Tilmann, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany

Tilmann Ditting, MD

• Cordasic, Nada, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany

Nada Cordasic

• Hilgers, Karl F., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany

Karl F. Hilgers, MD, FASN

• Linz, Peter, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany

Peter Linz, PhD

• Schiffer, Mario, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany

Mario Schiffer, MD, DrMed, MBA

• Schmieder, Roland E., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany

Roland E. Schmieder, MD, FASN

• Amann, Kerstin U., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany

Kerstin U. Amann, MD

• Veelken, Roland, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany

Roland Veelken, MD, DrMed

Background

Recently we demonstrated that reduced activity of the afferent renal neural pathway is associated with absent voltage-gated sodium Nav1.8 channels. Now we tested the hypothesis that Nav1.8 KO mice show elevated blood pressure and end organ damage with signs of increased sympathetic activity.

Methods

In Nav1.8 KO mice and C57BL6 (28th week of age), we measured blood pressure (BP), heart rate (HR), activity of renal afferent neurons (portion of highly active tonic neurons with renal afferents harvested from dorsal root ganglion neurons DRG Th11-L2), , afferent renal nerve activity (ARNA), renal sympathetic nerve activity (RSNA) as well as infiltration and fibrosis in heart and kidney tissue (deposition of collagen 1 and 4, Counts of CD 68 and CD 3 positive cells).

Results

Blood pressure of Nav1.8 KO mice (C57BL6J-Scn10atm1Jwo) was significantly elevated compared to wild type controls (11±4.8mmHg vers 98±5.2 mmHg; Nav1.8 KO mouse vs control * p<0.05.) Nav1.8 KO mice showed increased Collagen Type 1 and 4, CD 68 and CD 3 cells in the kidney and heart (t-test, * p<0.05). In Nav1.8 KO mice, only a single cell out of 70 showed a high firing frequency in neurons with dendrites from the kidney versus C57BL6 controls 28 out of 115 (Nav1.8 KO mouse vs control, z-test, *p<0.05). Eventually, all data suggested reduced ARNA with disinhibition of RSNA.

Conclusion

We demonstrate for the first time that the absence of a single specific sodium channel impairing afferent renal neural pathways leads to disinhibition of sympathetic nerve traffic with increased blood pressure and end-organ damage