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

Abstract

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.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.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%.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.Support or Funding InformationDFG Deutsche Forschungsgemeinschaft VE 104/4‐1This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.