Abstract 044: High Sodium Intake Impairs Afferent Sympathodepressory Pathways in Rats

Abstract

Afferent renal nerve pathways are likely involved the development of salt sensitive hypertension. We recently reported that intrarenal NaCl elicited a long-lasting sympatho-depression via a neuro-humoral TRPV1 dependent and tachykinin mediated renal afferent nerve pathway. We now wanted to test the hypothesis that high sodium intake impairs this afferent sympatho-depressory mechanism. Respective groups were put on tap water, 0.9 % saline for drinking or chow containing 8% NaCl. Cultured dorsal root ganglion neurons (DRG Th11-L2) of rats with renal afferents were investigated in current clamp mode to assess action potential generation during current injection. Rats were equipped with femoral catheters for blood pressure (BP) & heart rate (HR) assessment, drug application, a renal arterial catheter for intrarenal administration (IRA) of NaCl boli (10 % NaCl, 10 μl) or Capsaicin (CAP 3.3, 6.6, 10, 33*10-7 M, 10 μl) and a bipolar electrode for renal sympathetic nerve activity (RSNA) recordings; eventually an intravenous (iv) bolus of the NK1-receptor blocker RP67580 (10*10-3M, 15 μl) was administered. Results are mean±SEM. In neurons from rats on high salt diet, but not on 0.9 % saline or controls the relation of tonic highly active neurons to less active neurons shifted towards less active units (tap water -tonic/phasic: 22/15; saline - tonic/phasic: 28/18; 8% high salt - tonic/phasic: 14/21* P<0.05). However, cultured tonic renal neurons from rats on 0.9% saline or on high salt diet exhibited increased action potential (AP) production upon stimulation (control 13,3+/4 APs/600ms vs. saline 19,8+/-2,33* APs/600ms vs. high salt diet 22,2*+/-4,54 APs/600ms, control vs. experimental *p<0.05, mean+/-SEM). ). 10% NaCl boli IRA induced decreases of RSNA from baseline 4.1±0.6 μV*sec to 2.2±0.8 μV*sec impaired in rats on 8% NaCl. (Suppressed RSNA unmasked in all groups by an i.v. NK1-inhibitor) In rats on high salt diet highly active tonic neurons with renal afferents in vitro decreased at the expense of less active phasic neurons in spite of tonic neurons producing more action potentials upon stimulation. The sodium inducible long-lasting sympatho-depression via a neuro-humoral tachykinin mediated afferent renal nerve pathway was eventually impaired.