Abstract P188: (Pro)renin Receptor (PRR) Mediates High Fat Diet-induced Hypertension via Upregulation of Epithelial Sodium Channel & Aquaporin-2

Abstract

We hypothesized that the renal prorenin receptor (PRR) mediates high fat diet (HFD)-induced hypertension via enhancing expression of epithelial sodium channel (α-ENaC) and aquaporin-2 (AQP-2). C57BL/6 mice underwent right nephrectomy (n=12) and allocated to receive regular diet (RD, 12 kcal% fat, n=6) or a high-fat diet (HFD, 45 kcal% fat, n=6) for 10 weeks. HFD group received left renal subcapsular interstitial administration of PRR shRNA (n=3) or vehicle (n=3). BW, food and water intake, BP, UV and UNaV, renal interstitial fluid (RIF) angiotensin II (Ang II), and renal expressions of PRR, α-ENaC, AQP-2 were monitored. At baseline, there were no significant differences in BW, food and water intake, BP, UV or UNaV between different animal groups. At the end of the study, HFD mice had significant increase in food intake, systolic blood pressure (HFD 154.6 ± 2.181 mmHg, vs. RD 112.21 ± 4.684 mmHg, P<0.0.05), BW (HFD 43.2 ± 1.125 gm, vs. RD 31.9 ± 0.89654 gm, P<0.0.05), and significant reduction in UV (HFD 0.16 ± 0.042 ml, vs. RD 0.41 ± 0.061 ml, P<0.0.05) and UNaV (HFD 26.02 ± 3.652 μmol/day vs. RD 46.32 ± 5.236 μmol/day, P<0.0.05). Compared to RD, there were significant increases in mRNA and protein expressions of PRR (64% and 40%, P<0.01), α-ENaC (85% and 75%, P<0.05), AQP-2 (105% and 80%, P<0.05) in HFD alone mice respectively. Compared to HFD alone, HFD+ PRR shRNA treatment caused significant reductions in BP (108 ± 13.88 mmHg vs HFD 154.6 ± 2.181 mmHg), mRNA and protein expressions of PRR (33% and 50%, P<0.01), α-ENaC (49% and 56%, P<0.05), AQP-2 (30% and 29%, P<0.05) respectively. There were no changes in RIF Ang II between different animal groups. We conclude that PRR mediates HFD-induced hypertension via enhancing renal α-ENaC and AQP-2 expression independent of Angiotensin II.