Smooth Muscle βENaC Deletion Induces Moderate Hypertension and Renal Injury

Pressure-induced constriction (PIC) of renal arterial vasculature has been proposed to protect delicate glomerular capillaries from barotrauma. Previous studies from our laboratory have shown that degenerin proteins, including the beta subunit of the Epithelial Na+ Channel (βENaC), are important mediators of the PIC response.

We generated a smooth muscle βENaC knockout mouse model (SMC-βENaC-/-) to determine the importance of smooth muscle βENaC to the phenotype seen in βENaC hypomorph mice. We assessed renal interlobar vascular reactivity using myography, renal inflammation and injury using histology, blotting, ELISA and flow cytometry, and blood pressure using plethysmography.

We found that vasoconstrictor agonist (KCl, phenylephrine)-induced responses were similar in SMC-βENaC-/- and control mice. However, PIC responses in the renal interlobar artery were abolished in SMC-βENaC-/- mice. SBP was measured by tail-cuff plethysmography from 6 - 26 weeks of age, SBP was greater in SMC-βENaC-/- male (139±2 vs 120.3±1 mm Hg) and female (134±0.8 vs 117.3±3) mice compared to control littermates. We also found mild glomerular injury in SMC-βENaC-/- mice at 26 weeks. By 16 weeks of age, we found elevated levels of leukocytes, including M1/M2 macrophages, neutrophils, T-cells, and B-cells in renal arterial tissue in SMC-βENaC-/- mice.

Our findings provide additional evidence that vascular smooth muscle cell (VSMC) βENaC contributes to the transduction of the PIC response in renal vessels. Moreover, our findings provide evidence of the protective nature of PIC against vascular renal injury.