Abstract Body: Dorsal root ganglion (DRG) neurons project to peripheral tissues, including the kidney, and are the conduits for sensory information to the central nervous system. We have demonstrated that renal afferent nerve activity (ARNA) is increased in the deoxycorticosterone-salt (DOCA-salt) hypertensive rat and associated with increased renal inflammatory cytokines, such as interleukin-6 (IL-6). However, the mechanisms of increased ARNA and role of renal inflammation remain unclear. We hypothesized that baseline firing rate would be increased in DOCA-salt renal DRGs, and IL-6 activates renal sensory nerves independent of DOCA treatment. To test our hypothesis, we isolated renal-specific DRG (r-DRG) neurons from normotensive (n=38 cells) and DOCA-salt (n=52 cells) male rats for whole-cell patch clamp recordings. Hypertensive rats were generated as previously described by administering 100mg DOCA (s.c. implant) with 0.9% saline drinking water for 21 days. Normotensive controls were administered water and vehicle implant. R-DRGs were labeled with intrarenal injection of retrograde tracer DiI 6 days prior to study end. DRGs from T10-L1 were isolated at necropsy, enzymatically digested, and cultured overnight. The DiI+ rDRGs were recorded within 24 hours using the whole-cell patch-clamp technique (-100-300 pA current steps). Finally, dose-response (0.4 – 40ng/mL) was recorded with IL-6. Data were analyzed by two-way ANOVA. Data presented as mean±SEM. Mean r-DRG firing rate were increased compared to control (4.8±1.0 vs. 2.6±0.7 Hz at 300pA). IL-6 similarly elicited dose-dependent excitatory responses in 65.2.% of DOCA-salt r-DRGs, and 66.7% of control. IL-6 also produced an inhibitory response in 34.8% of DOCA-salt r-DRGs and 33.3% of control. Interestingly, the dose-dependent inhibitory response to IL-6 was lower (p<0.05) in DOCA-salt vs. control. Overall these data partially supported our hypothesis that DOCA-salt hypertension is associated with increased r-DRG neuronal firing rate. However, the response to IL-6 did not support our initial hypothesis, where IL-6 elicited both inhibitory and excitatory effects in r-DRGs. Interestingly, the r-DRGs inhibited by IL-6 are less sensitive in DOCA-salt vs. control, suggesting a disinhibitory effect on response to IL-6. Loss of inhibitory response to IL-6 and other cytokines may be a driver of sustained increase in ARNA in addition to the increased overall r-DRG baseline firing rate with DOCA-salt treatment.