Urinary Angiotensinogen is Essential for Renal Potassium Handling

Abstract

Apart from the well‐known systemic renin‐angiotensin system (RAS), the urinary RAS acts as a local autocrine/paracrine system along the nephron. The regulation of renal K+ handling by systemic vs urinary RAS remains unclear. Liver‐specific (Alb‐Cre) angiotensinogen knockout (LKO) and liver + proximal tubule (Alb‐Cre + KAP‐Cre) angiotensinogen knockout (DKO) were utilized in this study. WT, LKO, and DKO mice were kept on either a regular diet (RD) or a high K diet (HK; 5% K+) for 10 days. Mice were acclimated to metabolic cages twice before collecting urine for 24 hours. Mice were then euthanized to collect blood and kidneys. Plasma and urinary [Na+] and [K+] were measured by flame photometry. Plasma and urinary angiotensin II (Ang II) concentrations were measured by ELISA (Enzo Life Sciences). Plasma and urinary aldosterone (Aldo) concentrations were measured by ELISA (DRG Diagnostics). Urinary creatinine (Cr) concentrations were measured by colorimetric assays (Cayman Chemical). Plasma [Ang II] was significantly lower in LKO, compared to WT, and the value in DKO was not significantly different from zero. Urinary [Ang II] was significantly lower in DKO compared to WT and LKO. Plasma [K+] was significantly higher in DKO but not LKO compared to WT on HK. Urinary K:Cr ratio was significantly lower in DKO compared to WT on HK. However, plasma and urinary [Aldo] were not different between DKO and WT on HK. Overall, our results showed that urinary RAS but not systemic RAS plays an essential role in renal K handling.Support or Funding InformationThis project was funded by F30 DK108456.