Abstract Body: Renal afferent nerves are reported to mediate the progression of hypertension in preclinical models, putatively via an aberrant increase in activation. The underlying source of this nerve activation is unknown but we hypothesized renal inflammatory cytokines are a primary driver. We previously reported interleukin 6 (IL-6) is increased in the kidneys of hypertensive rats, and intrarenal administration of IL-6 can activate renal afferent nerves. Though these data are promising, the direct effects of IL-6 on afferent renal nerves remain unclear. We hypothesized that isolated renal afferent neurons from hypertensive rats will have increased activity and responsiveness to inflammatory cytokine IL-6 compared to normotensive controls. To test our hypothesis, we tested the direct effects of interleukin-6 (IL-6) on renal afferent nerve action potentials (AP) generated in freshly isolated dorsal root ganglion (DRG) neurons. To model salt-sensitive hypertension, uninephrectomized rats (n=6) were administered deoxycorticosterone acetate (DOCA; 100mg, sc) and 0.9% saline for drinking water for 21 days. Control rats (n=6) were uninephrectomized. To label renal afferent nerves, neuronal tracer DiI was introduced by intrarenal injection 6 days prior to DRG collection. DRGs from T10-L1 were isolated, enzymatically digested and dissociated, and cultured overnight for whole-cell patch-clamp the following day. DiI-positive neurons from both control and DOCA rats generated AP during the delivery of 100, 200, and 300 pA current steps. Data were analyzed by two-way, repeat-measures ANOVA (α=.05). At baseline, DOCA neurons had a higher (p<0.05) mean AP frequency compared to controls (no difference in AP mean peak amplitude or AP duration). In both groups, increasing concentrations of IL-6 (0. 4, 4, and 40 ng/ml) elicited a dose-dependent increase in AP peak amplitude compared to baseline. No difference was detected in IL-6 responses between DOCA and controls. Overall, these data supported our original hypothesis that pro-inflammatory cytokine IL-6 would increase renal afferent nerve activity, and that said activity is increased in hypertensive DOCA-salt rats. IL-6 accumulation triggered by end organ damage due to hypertension might lead to increased afferent renal nerve activity, which exacerbates the hypertensive phenotype through a sympatho-excitatory response. Additional measurements of isolated DRG responses to pro-inflammatory mediators are underway for direct comparison.