Kidney Week

Abstract: TH-PO510

Interleukin 6 plus High Salt Increases Functional Epithelial Sodium Channel Activity

Session Information

• Fluid and Electrolytes: Basic - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Wynne, Brandi M., Emory University School of Medicine, Atlanta, Georgia, United States

Brandi M. Wynne,

• Buncha, Vadym, Medical College of Georgia, Augusta University, Augusta, Georgia, United States

Vadym Buncha,

• Cherezova, Alena, Medical College of Georgia, Augusta University, Augusta, Georgia, United States

Alena Cherezova,

• McCarthy, Cameron G., Augusta University, Augusta, Georgia, United States

Cameron G. McCarthy,

• Hecht, Gillian Grace, Emory University, Atlanta, Georgia, United States

Gillian Grace Hecht,

• Wenceslau, Camilla F., The University of Toledo, Toledo, Ohio, United States

Camilla F. Wenceslau,

• Hoover, Robert S., Emory University, Atlanta, Georgia, United States

Robert S. Hoover,

• Mamenko, Mykola, Augusta University, Augusta, Georgia, United States

Mykola Mamenko,

Background

Hypertension (HTN) is characterized by increased sodium (Na⁺) reabsorption, and increased cytokines such as interleukin 6 (IL6). Our data suggests that IL6 infusion increases blood pressure (BP) and distal nephron Na⁺ transporter expression/activity, with an early reduction in urinary Na⁺ excretion (U_Na). However, whether this reduction in U_Na is mediated by epithelial sodium channel (ENaC) activity is unknown. We hypothesize that IL6 increases ENaC activity.

Methods

Mice were treated with IL-6 (16ng/hr, 0.1%BSA) or vehicle via osmotic minipump, and fed high salt (HS, 4%) diet for 1 or 3 days (1D, 3D). ENaC open probability (P_o), functional expression (fN) and functional activity (fNP_o) were assessed in split open tubules (cortical collecting duct, CCD) from IL6-treated (IL6+HS) and vehicle (HS) mice. Data are expressed as mean±SEM, where SEM is patch number in at least 3 mice per group.

Results

We observed a trending increase in ENaC fN in CCD from IL6+HS after only 1D, reaching significance by 3D (0.94±0.14, n=44 vs.0.63±0.08, n=63, p<0.05), compared to HS only. Although open probability (P_o) was not increased, fNP_o was almost doubled in IL6+HS treated mice after 1D (0.24±0.08, n=51 vs. 0.12±0.04, n=62), and significantly increased after 3D (0.28±0.07, n=44 vs. 0.13±0.04, n=63, p<0.05).

Conclusion

Here, we show that increased IL6 causes trending increases in ENaC fN and fNP_o, after only 1D. These data correlate with our data showing U_Na is reduced in the first 24 hours. Continued IL6+HS treatment significantly increased both fN and fNP_o by day 3, also correlating with increases in ENaCα/γ expression and BP (by D3). We later see increased U_Na, indicating pressure natriuresis. These data suggest that, remarkably, IL6 may activate distal nephron Na⁺reabsorption, even with increased dietary salt. These data reveal a novel role for IL6-mediated changes in U_Na excretion, leading to salt-sensitive HTN.

Figure 1. Representative continuous current traces from cell-attached patches in CCD.

Funding

• NIDDK Support