We have demonstrated a critical role of CNS Gαi2 proteins in sodium homeostasis and blood pressure regulation. These studies tested the hypothesis that increased total body sodium activates the afferent renal afferent nerves to evoke sympathoinhibition to facilitate sodium homeostasis and normotension, via a PVN signal transduction pathway involving Gαi2 proteins, in the Sprague-Dawley (SD) rat.Design and Method:
Conscious SD rats, having undergone sham or renal afferent nerve denervation (Renal-CAP) underwent an IV volume expansion (VE; 5% BW), HR, MAP, natriuresis and PVN neuronal activation were assessed (N = 5/group). Radiotelemetred naïve, Groups of sham or Renal-CAP treated Sprague-Dawley rats were fed a 0.6% (NS) or 8% NaCl (HS) diet for 21 days and MAP was continuously monitored. On day-21 plasma and renal NE content, PVN Gαi2 protein expression and NCC activity (peak natriuresis to IV hydrochlorothiazide (HCTZ; 2 mg/kg infusion) was assessed (N = 5/group).Results:
Afferent renal nerve ablation attenuated the natriuretic and PVN parvocellular activation responses to IV VE (peak UNaV [μeq/min]; Sham 43 ± 4 vs Renal-CAP 26 ± 6, P < 0.05, PVN neuronal activation [c-fos positive cells]; Medial parvocellular Sham 54 ± 8 vs Renal-CAP, 22 ± 5 P < 0.05) and evoked increased blood pressure (MAP 90 min post-VE [mmHg] Sham 118 ± 3 vs Renal-CAP 132 ± 4, P < 0.05). In Renal-CAP versus sham or naïve animals we observed significantly attenuated HS-evoked sympathoinhibition (P < 0.05), abolishment of PVN Gαi2 protein up regulation and down regulation of NCC activity (peak UNaV to HCTZ [μeq/min] naïve NS 9.2 ± 0.5, naïve HS 7.0 ± 0.4, Renal-CAP HS 10.3 ± 0.8).Conclusions:
The renal afferent nerves mediate natriuresis and blood pressure regulation during an acute challenge to fluid and electrolyte homeostasis in conscious Sprague-Dawley rats. During HS intake the renal afferent nerves prevent the development of salt-sensitive hypertension via a mechanism involving increased activity of the renal afferent nerves to potentiate sympathoinhibitory pathways, which involves up regulation of PVN Gαi2 proteins, to facilitate natriuresis.