Kidney Week

Abstract: TH-PO0294

Dysregulation of the Renal Autonomous Innervation with Elevated Blood Pressure Due to Lack of Sodium Nav1.8 Channels

Session Information

• Hypertension and CVD: Mechanisms
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1601 Hypertension and CVD: Basic

Authors

• Hutter, Eva, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Eva Hutter, MSc

• Ditting, Tilmann, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Tilmann Ditting, MD

• Hilgers, Karl F., Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Karl F. Hilgers, MD, FASN

• Morath, Christian, Paracelsus Medizinische Privatuniversitat - Nurnberg, Nuremberg, BY, Germany

Christian Morath, MD

• Schmieder, Roland E., Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Roland E. Schmieder, MD, FASN

• Schiffer, Mario, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Mario Schiffer, MD, DrMed, MBA

• Amann, Kerstin U., Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Kerstin U. Amann, MD

• Veelken, Roland, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Roland Veelken, MD, DrMed

• Rodionova, Kristina, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, BY, Germany

Kristina Rodionova, MD

Background

Reduced activity of cultivated neurons with renal axons is associated with absent voltage-gated sodium Nav1.8 channels. Now we tested the hypothesis that this monogenetic deletion is accompanied by directly recorded increased renal sympathetic nerve activity (RSNA) and decreased sympathoinhibitory afferent renal nerve activity (ARNA) in Nav 1.8 KO mice in vivo.

Methods

In Nav1.8 KO mice and C57BL6 (28^th week of age; n=4), we analyzed directly recorded renal sympathetic nerve activity (RSNA assessing burst amplitude & burst duration) and afferent renal nerve activity (ARNA; after ganglionic blockade). Furthermore, we measured blood pressure (BP), heart rate (HR), eventually assessed transdermally the glomerular filtration rate (GFR) and signs of renal fibrosis.

Results

As a sign of activity, burst frequency of RSNA was higher in Nav 1.8 KO mice as compared to controls: during a period of 400 sec, we counted a median burst activity in Nav 1.8 mice of 6870 bursts (25%: 5532.5; 75%:7665.0) versus in controls 4879.5 (25%: 4628.000;75%; 5967.000). The Mann-Whitney Rank Sum Test suggested a statistically significant difference between Nav1.8 and controls (P=0.002). The test for normality was passed (P = 0.198). Burst were significantly broader in Nav 1.8 mice as in controls. Median spike production of ARNA was significantly altered in Nav 1.8 KO mice (170 spikes/min) as compared to controls (1384 spikes/min). Blood pressure of Nav1.8 KO mice was significantly elevated compared to controls. Nav1.8 KO mice showed signs of renal fibrosis (increased Collagen Type 1 and 4, CD 68 and CD 3 cells). However, GFR was yet not decreased in Nav1.8 KO mice at 28^th week of age as assessed transdermally.

Conclusion

The hypertensive Nav1.8 KO mouse model suggests for the first time one conclusive mechanism to explain neurogenically induced elevated blood pressure by the renal autonomous innervation. These findings will help to better understand renal nerve ablation and probably open the path to new antihypertensive strategies.

Funding

• Other NIH Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20251t1zrbbm