Glomerular Injury Induced by Daily Exposure to the Low-Frequency Component of Environmental Noise via Endothelin Signaling in Mice

Epidemiological studies suggest that environmental noise is associated with kidney dysfunction in humans; however, the underlying characteristics, such as frequency, intensity, and duration, remain unclear. Effects of exposure to whole environmental noise generated by electric devices (all frequencies), low-frequency noise (LFN; ≤100 Hz), and non-LFN (>100 Hz) for 12-h/day for 5 consecutive days on kidney function were investigated in mice. Exposure to whole environmental noise at ≤ 88 dBA elevated serum creatinine and blood urea nitrogen (BUN). This effect was reproduced by LFN exposure alone (≤70 dBA) but not by non-LFN exposure (≤87 dBA). Biochemically, LFN increased renal expression of endothelin-1 and endothelial nitric oxide synthase, biomarkers of vascular injury. Histologically, LFN increased glomerular and mesangial areas and thickened glomerular basement membranes. Pharmacological inhibition of endothelin signaling reduced serum creatinine and BUN levels and mitigated the LFN-induced glomerular damage. Our findings provide the first direct evidence that the low-frequency component of environmental noise, well below the murine audible range, induces glomerular injury via endothelin signaling and results in kidney dysfunction in mice. Considering prior human cross-sectional studies, these murine findings warrant further investigation to determine their translational relevance in humans.