Abstract: PO1831
Bradykinin Reduces Long-Lasting TRPV1-Mediated Inward Currents in Afferent Nonfiring Renal Neurons
Session Information
- Hypertension and CVD: Mechanisms
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Rodionova, Kristina, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
- Forray-Strauss, Christina, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
- Ditting, Tilmann, 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
- Cordasic, Nada, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
- Linz, Peter, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
- Ott, Christian, 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
- Schiffer, Mario, 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, Bayern, Germany
Background
Bradykinin had been reported to be sympathoexcitatory via renal afferent nerves. Hence we tested the hypothesis that bradykinin directly stimulates cultivated renal neurons with afferent axons.
Methods
Dorsal root ganglion neurons (Th11-L2) of rats were investigated in voltage clamp mode to assess inward currents and current clamp mode to assess action potential (AP) generation [neurons classified as tonic (high AP generation upon stimulation), phasic (AP < 5 upon stimulation) or no firing]. Stimulation of TRPV1 receptors by protons (pH 6) with and without the addition of bradykinin (1, 10,100 µM). 111 DRG renal neurons retrogradely stained with DiI for investigation.
Results
Bradykinin (BK) alone did not induce inward currents nor APs. Proton stimulation (pH 6) of TRPV1 significantly augmented long-term inward currents (baseline -0.360±0.09nA vs. -1.39±0.34nA, p<0.05, mean±SEM) and increased action potential production in tonic neurons (0 APs/10s vs. 9.57±1.89 APs/10s*, p<0.05, mean±SEM). However, the co-stimulation of renal neurons with protons and BK had any effect only in one specific subgroup of renal neurons: it significantly decreased long-lasting currents in non firing neurons (ΔI upon stimulation with 100µM BK&pH6: -0.129±0.02nA, 10µM BK&pH6: -0.119±0.03nA, 1µM BK&pH6: -0.063±0.02 nA versus pH 6: -0.312±0.06nA*, *p<0.05, mean±SEM).
Conclusion
Bradykinin was only able to reduce long-lasting, TRPV1 dependent inward currents in non-firing renal neurons. Alterations of inward currents are likely involved in the release of neurogenic proinflammatory peptides (SP, CGRP). Hence, bradykinin might impair the release of neuropetides from intrarenal axons of a specific subgroup of renal afferent neurons.