Vasopressinergic neurons which project from the paraventricular nucleus to the spinal cord (Hallbeck & Blomqvist, 1999) facilitate renal (Yang & Coote, 2006) and lumbar (Antunes et al. 2006) sympathoexcitation (SNA) by the release of AVP and glutamate. Increased lumbar SNA by acute salt loading is partially mediated by spinal V1 receptor activation (Antunes et al. 2006). Our lab has shown that Wistar rats fed a high Na⁺ (HNa⁺) diet from weaning to adulthood exhibited an enhanced blood pressure (BP) and renal sympathoexcitatory (RSNA) response to lateral intracerebroventricle infusion of angiotensin III (Houghton & Johns, 2007). The pressor response was attenuated by peripheral V₁ blockade, but the RSNA response remained, which suggested a role for spinal V1 receptor activation. It was hypothesised that the RSNA response to intrathecal (IT) infusion of vasopressin or glutamate would be augmented in HNa⁺ rats. Four week old male Wistar rats were fed a normal Na⁺ (0.3%, NNa⁺) or high Na⁺ (3.0%) diet for six weeks and anaesthetised by a 1 ml chloralose/urethane (16.5/250mg/ml) I.P. injection. Cannulae were inserted into the right femoral artery (BP measurement) and vein (saline/anaesthetic infusions). An intrathecal (IT) cannula filled with artificial cerebrospinal fluid (aCSF, pH 7.4) was inserted at vertebra L3 and the tip placed at T13. The left kidney was exposed and recording electrodes were sealed onto a renal nerve. The RSNA response to IT AVP (1, 5, 10, 20μM; 10 μL/2min; NNa⁺ = 7, HNa⁺ = 5) or IT glutamate (10, 20, 50, 100mM, 10 μL/2min; NNa⁺ = 6, HNa⁺ = 5) was recorded for 15 min. RSNA was averaged over a 2-min period during baseline measurements and over 60 seconds at the peak RSNA response. Background RSNA noise recorded after the experiment was terminated was subtracted from the original values. Peak RSNA was calculated as percentage of baseline values prior to each IT infusion. Means ± S.E.M. were compared by ANOVA. Baseline RSNA (μV/s) was similar between groups (NNa⁺:13±2 vs HNa⁺: 9±2). The peak rise in RSNA after IT AVP infusion was greater in HNa⁺ at 1μM* (NNa⁺: 100±2% vs HNa⁺: 108±2.0%) and 5μM* (NNa⁺: 103 ± 1% vs HNa⁺: 110±2%). A sensitised RSNA response to IT glutamate infusion was also observed in HNa+ after 10mM** (NNa⁺: 98 ± 1% vs HNa⁺: 117±5%), 20mM* (NNa⁺: 105±4% vs HNa⁺: 130±12%), 50mM** (NNa⁺: 109±2% vs HNa⁺:147±6%) and 100mM** (NNa⁺: 126±8% vs HNa⁺: 178±26%). All comparisons reached significance of *P<0.05 or **P<0.01. These results show that HNa⁺ intake sensitises the RSNA response to IT AVP and glutamate infusion. This suggests that spinal AVP- and glutamate-mediated RSNA may be enhanced and could contribute to the development of hypertension due to long term high dietary Na⁺ intake.