SYMPATHOINHIBITORY AFFERENT NERVE PATHWAYS FROM THE KIDNEY IN RATS – PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL EFFECTS OF SODIUM

Objective: High salt diet might impair afferent renal nerve pathways which increase renal sympathetic nerve activity (RSNA) in hypertension. We reported on a specific long lasting (>90 min) sympatho-inhibitiory reflex depending on TRPV1 receptors elicited by intrarenal afferent nerve stimulation. We wanted to test the hypothesis that sodium influences (presumably via NaX channels) this renal afferent sympatho-depressory mechanism which is impaired during high salt diet. Design and method: Three groups of rats were put on tap water, 0.9% saline for drinking or a high salt chow containing 8% NaCl. Animals were equipped with femoral catheters (blood pressure (BP) & heart rate (HR)), renal arterial catheters for intrarenal administration (IRA) of high salt boli (10% NaCl, 10 μl) or the TRPV 1 receptor agonist capsaicin (CAP 3.3, 6.6, 10, 33∗10-7 M, 10 μl) and bipolar electrode for RSNA recordings. 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. Results: mean±SEM. Results: IRA with high salt or IRA CAP boli 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). Interestingly, suppressed RSNA in groups renally injected with high salt boli or CAP could be unmasked by the systemic administration of the tachykinin NK1-blocker RP67580 (10∗10-3 M, 15 μl). Decreases of RSNA due to 10% NaCl boli were impaired after high salt chow. Renal neurons produced action potentials (3.5±0.8, ∗p<0.05) during exposure to NaCl. In neurons from rats on a high salt diet, the relation of tonic highly active neurons to less active neurons shifted towards the latter. (tap water -tonic/phasic: 22/15; saline - tonic/phasic: 28/18; 8% high salt - tonic/phasic: 14/21∗ P<0.05). Conclusions: Increased intrarenal sodium concentrations likely induce long-lasting sympatho-depression via neuro-humoral TRPV1 dependent, and tachykinin mediated afferent renal nerve pathways, impaired during increased ingestion of sodium chloride: control of RSNA is weakened while the afferent pathways exhibit a reduced number of highly active neurons.