Abstract: SA-PO1104

Intrarenal High Salt Administration Causes Tonic Inhibition of Renal Sympathetic Nerve Activity (RSNA)

Session Information

  • Salt and Hypertension
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Hypertension

  • 1101 Hypertension: Basic and Experimental - Neural and Inflammatory Mechanisms

Authors

  • Hindermann, Martin, Dept. of Nephrology, Friedrich-Alexander-University Erlangen, Erlangen, Germany
  • Rodionova, Kristina, Dept. of Nephrology, Friedrich-Alexander-University Erlangen, Erlangen, Germany
  • Dietz, Amelie, Dept. of Nephrology, Friedrich-Alexander-University Erlangen, Erlangen, Germany
  • Ditting, Tilmann, Dept. of Nephrology, Friedrich-Alexander-University Erlangen, Erlangen, Germany
  • Ott, Chrstian, Dept. of Nephrology, Friedrich-Alexander-University Erlangen, Erlangen, Germany
  • Schmieder, Roland E., Dept. of Nephrology, Friedrich-Alexander-University Erlangen, Erlangen, Germany
  • Amann, Kerstin U., Dept. of Nephropathology, Friedrich-Alexander-University Erlangen, Erlangen, Germany
  • Veelken, Roland, Dept. of Nephrology, Friedrich-Alexander-University Erlangen, Erlangen, Germany
Background

Afferent renal nerve fibers from the kidney likely counterregulate salt sensitive blood pressure increases by decreasing renal sympathetic nerve activity. We recently reported on a long-lasting tonic sympatho-inhibition due to intrarenal afferent renal nerve stimulation eliciting a TRPV1 dependent neuro-humoral pathway. We wanted to test the hypothesis that sodium influences this afferent sympatho-depressory mechanism.

Methods

Groups of anesthetized SD rats (n=8) were equipped with femoral catheters (blood pressure (BP) & heart rate (HR) recording, drug application), a renal arterial catheter for intrarenal administration (IRA) of high salt (10 % NaCl, 10 µl) or Capsaicin (CAP 3.3, 6.6, 10, 33*10-7 M, 10 µl) and a bipolar electrode for RSNA recordings; eventually an intravenous (iv) bolus of the NK1-receptor blocker RP67580 (10*10-3M, 15 µl) was given. Cultured dorsal root ganglion neurons (Th11-L2) of rats with renal afferents were investigated in current clamp mode to assess action potential generation or in voltage clamp mode to investigate inward currents during 10 sec exposure to 4.5 % NaCl or equi-osmotic 20% mannitol. Results are given in mean±SEM.

Results

IRA high salt and IRA CAP decreased RSNA from baseline 4.1±0.6 µV*sec to 2.2±0.8 µV*sec (10% NaCl, p<0.05) and 3.9±0.5 µV*sec to 0.9±0.2 µV*sec (CAP, p<0.01). Suppressed RSNA in high salt groups and CAP could be unmasked by systemic (i.v.) administration of the NK1-blocker (2.7±1.8 µV*sec to 5.8±2.2 µV*sec; p<0.05 (10% NaCl); 1.0±0.2 µV*sec to 6.1±1.5 µV*sec; p<0.01 (CAP)). Cultured renal neurons exhibited production of action potentials (3.5±0.8*, from baseline, p<0.05) and increased sustained inward currents from baseline during exposure to NaCl 4.5 % (-10708.8±3546.5 pA*, from baseline, p<0.05). No responses to mannitol 20%.

Conclusion

Increased intrarenal sodium concentrations might induce long-lasting sympatho-depression via a neuro-humoral TRPV1 dependent and tachykinin mediated afferent nerve pathway from the kidney. Impairment of this sympatho-depressory mechanism could be involved in salt sensitive hypertension.