Kidney Week

Abstract: TH-PO0786

Loss of Bradykinin B1-B2 Signaling Disrupts Renal Afferent Feedback and Drives Sympathoexcitation

Session Information

• CKM Axis: Vascular Dysfunction, Atherosclerosis, and Heart Failure in Kidney Diseases
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Cardiovascular-Kidney-Metabolic Health

• 601 Cardiovascular-Kidney-Metabolic Health: Basic

Authors

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

Eva Hutter, MSc

• Klose, Lars Peter, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, BY, Germany

Lars Peter Klose

• Bader, Michael, Max-Delbruck-Centrum fur Molekulare Medizin in der Helmholtz-Gemeinschaft Experimental and Clinical Research Center, Berlin, BE, Germany

Michael Bader

• Ditting, Tilmann, Klinikum Nurnberg Sud, Nuremberg, BY, Germany

Tilmann Ditting, MD

• Hilgers, Karl F., Universitatsklinikum Erlangen, Erlangen, BY, Germany

Karl F. Hilgers, MD, FASN

• Linz, Peter, Universitatsklinikum Erlangen, Erlangen, BY, Germany

Peter Linz, PhD

• Schmieder, Roland E., Universitatsklinikum Erlangen, Erlangen, BY, Germany

Roland E. Schmieder, MD, FASN

• Morath, Christian, Klinikum Nurnberg Sud, Nuremberg, BY, Germany

Christian Morath, MD

• Schiffer, Mario, Universitatsklinikum Erlangen, Erlangen, BY, Germany

Mario Schiffer, MD, MBA

• Amann, Kerstin U., Universitatsklinikum Erlangen, Erlangen, BY, Germany

Kerstin U. Amann, MD

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

Roland Veelken, MD, DrMed

• Rodionova, Kristina, Universitatsklinikum Erlangen, Erlangen, BY, Germany

Kristina Rodionova, MD

Background

Renal afferent nerves restrain renal sympathetic nerve activity (RSNA) via a negative feedback loop. Bradykinin signaling modulates neuronal excitability in sensory pathways. We tested the hypothesis that combined absence of bradykinin B1 and B2 receptors in respective KO mice alters renal afferent signaling and autonomic balance.

Methods

RSNA was significantly increased in B1/B2 double knockout mice, with a median burst activity of 1764+322 bursts/min versus 732+110 bursts/min in controls. In contrast, ARNA was significantly reduced to approximately 109+22 spikes/min versus 1384+263 spikes/min in controls (n=4; p<0.05). Electrophysiologically, only 2,2 % of renal-projecting DRG neurons exhibited tonic firing behavior in B1/B2 receptor KO mice versus 18,1% in controls (total of 177 neurons, p<0.05, z-test), indicating a profound loss of the high-activity sensory phenotype.

Results

RSNA was significantly increased in B1/B2 double knockout mice, with a median burst activity of 1031 bursts/min versus 732 bursts/min in controls. In contrast, ARNA was significantly reduced to approximately 119 spikes/min versus 1384 spikes/min in controls (p<0.05). Electrophysiologically, only 2,2 % of renal-projecting DRG neurons exhibited tonic firing behavior in B1/B2 receptor KO mice versus 18,1% in controls (total of 177 neurons, p<0.05, z-test), indicating a profound loss of the high-activity sensory phenotype.

Conclusion

Combined absence of bradykinin B1 and B2 receptors led to collapse of renal afferent signaling and poorly controlled sympathetic activation. Loss of tonic firing together with reduced ARNA identifies bradykinin signaling as essential for maintaining the renal afferent feedback loop. The similarity to findings in Nav1.8-deficient mice, in which repetitive action potential firing is impaired, suggests convergence of receptor signaling and Nav1.8-dependent excitability on a common mechanism sustaining high tonic afferent activity.