Renal Sodium Hydrogen Exchanger Isoform 3 (NHE3) is an apical membrane protein which mediates the reabsorption of Na⁺ from, and the extrusion of H⁺ into, the lumen of the proximal tubule. Previous studies have demonstrated that inhibitory agents such as PTH cause a retraction of NHE3 from the top of the microvilli to inter-microvillar cleft regions (Yang et al. 2004). Activation of the renal sympathetic nerves directly increases proximal tubular fluid reabsorption and one mechanism may be a stimulation of NHE3. The aim of this study was to evaluate whether changes in renal nerve activity could also modulate movement of NHE3 into the inter-microvillar clefts. In vivo studies were performed on chloralose/ urethane (1 ml, 16.5:250 mg/ml I.P.) anaesthetised Wistar rats. Cannulae were placed in a femoral artery to measure blood pressure and in the femoral vein to infuse saline and inulin. Using flank incisions, the right ureter was cannulated; the left kidney was exposed, it’s ureter cannulated and it was subjected to surgical denervation. After 2h stabilisation, two 15 min clearances were undertaken, the kidneys were excised and placed on ice. The cortices were dissected free and brush border membranes were obtained using Mg²⁺ precipitation and differential centrifugation (Weinman et al. 1987). The membranes were subjected to SDS-PAGE and after Western blotting, NHE3 was quantified and identified. Data (means±SEM) were subjected to Student’s t-test and significance taken when P<0.05. Western blot analysis showed that NHE3 protein abundance was reduced 3-fold after denervation in relation to the innervated kidney (n=6). There was a significantly higher (P<0.01) urinary Na⁺ excretion in the denervated kidney (4.1±1.2μmol/min/kg) as opposed to the innervated kidney (1.0±0.2μmol/min/kg). Fractional sodium excretion was also significantly elevated (p<.01) in the denervated kidney (0.7±.02% vs 0.2±.05%). GFR was similar in both the innervated and denervated kidneys at 3.3±0.3 and 3.2±0.3ml/min/kg, respectively. The data show that renal denervation increased sodium excretion and decreased apical membrane NHE3 abundance, independently of renal haemodynamics. This suggests that changes in RSNA may affect trafficking of NHE3 between microvilli and other subcellular domain.