Renal impairment is a common and independent risk factor of morbidity and mortality in patients with chronic heart failure (CHF). We hypothesized that impaired renal function is mediated, in part, by the cardiac sympathetic afferent reflex (CSAR), a cardiogenic sympatho-excitatory reflex that is activated during an acute myocardial infarction (MI) or in CHF. We previously demonstrated that chronic and selective CSAR denervation at the time of MI by epicardial application of resiniferatoxin (RTX) markedly reduced renal sympathetic nerve activity (RSNA) in rats ~10 weeks post MI (1). We evaluated renal function by simultaneously measuring blood K+, creatinine and blood urea nitrogen (BUN) in sham-operated or MI rats treated with epicardial application of RTX (50ug/ml) or vehicle at ~6 weeks, ~12 weeks and ~18 weeks post MI. Compared to sham-operated rats, MI+vehicle and MI+RTX rats had normal blood K+, creatinine and BUN at ~6 weeks and ~12 weeks post MI, indicating that renal dysfunction may less likely occur at the early and middle stages of CHF. However, compared to the 12 week post MI time point, plasma K+, creatinine and BUN were significantly increased at the 18 weeks post MI (K+: 4.10±0.08 to 4.70±0.07 mmol/L; Creatinine: 0.47±0.02 to 0.70±0.05 mg/dL; BUN: 22.9±0.7 to 30.8±1.7 mg/dL; P<0.05, n=13), suggesting that renal dysfunction occurs in the late stage of CHF. Compared to MI+vehicle at ~18 weeks post MI, MI+RTX rats at the same time point exhibited almost normal blood K+ (4.19±0.09 mmol/L), creatinine (0.55±0.04 mg/dL) and BUN (25.8±1.1 mg/dL), suggesting improved renal function in RTX-treated MI rats. Infarct size between MI+RTX and MI+vehicle groups were similar, excluding the possibility that differences in infarct size caused the difference in renal function between these two groups. In order to evaluate the potential molecular changes in the kidneys of the post-MI rats treated with epicardial RTX, we harvested the kidney tissues from the above sham, MI+Vehicle and MI+RTX rats (n=4-5/per group) at ~18 weeks post MI to run the mRNA sequence analysis. Our data demonstrated that compared to the age-matched sham rats, several renal injury and inflammatory gene markers (Havcr1 also named KIM-1, ATF3, CXCL10, IGFBP1, SOCS3, HMOX1, LCN2 also named NGAL, BTG2, LAMC2, RND1) were significantly upregulated by 20-66 fold in MI+vehicle rats ~18 weeks post MI. Compared to MI+vehicle, CSAR ablation by RTX selectively reduced the gene expression of Havcr1 (a specific proximal tubular damage marker) by 4 fold, indicating a potential protective effect by RTX on proximal tubular dysfunction in MI rats at ~18 weeks post MI. These data suggest that pathological activation of the CSAR in the post-MI state plays a critical role in mediating the potential renal damage occurring in the late stages of CHF.