PRR is expressed in renal glomeruli and tubules. We hypothesized that PRR plays a role in regulation of renal sodium reabsorption via modulation of ENaC expression. Male Sprague-Dawley (200-250g) rats were fed normal sodium diet. BP, and 24h urine collections were obtained before and one week after right uninephrectomy. Renal hemodynamic and excretory functions were assessed before and after left renal subcapsular interstitial administration of 5% D5W (V), scrambled PRR shRNA (Ssh) or PRR shRNA (Sh) (n=6 each treatment). Renal PRR and α-, β-, and γ-ENaC expressions were evaluated. There were no significant differences in blood pressure or renal hemodynamic function among treatments. Compared to V or Ssh, Sh caused significant reduction in renal PRR mRNA and protein by 77 and 76% in cortex and 82 and 75% in medulla, respectively. Sh treated rats had significant increase in 24h urinary volume (V 17 ± 1.37, Ssh 17.5 ± 1.29 vs. Sh 24.3 ± 1.19 ml/24hr, p<0.05), and sodium excretion (V 220.03 ± 16.94, Ssh 232.6 ± 17.2 vs Sh 516.9 ± 14.8 μmol/24hr, p<0.001). There were no significant differences in the fractional excretion of lithium or proximal tubular sodium reabsorption between all groups. Compared to V and Ssh, Sh caused significant reduction in distal tubular sodium reabsorption (V 4.5 ± 0.1%, Ssh 4.2 ± 0.2%, vs Sh 1.73 ± 0.19%, respectively, p<0.001) and distal tubule ENaC mRNA and protein expression (α-ENaC 51 and 58%, p<0.05; β-ENaC 74 and 57%, p<0.05 and γ-ENaC 74 and 53%, p<0.05, respectively). We conclude that PRR contributes to distal renal sodium reabsorption via enhancing distal tubule ENaC expression without any changes in renal hemodynamic function.