Pharmacological activation of AMPK prevents aircraft noise induced oxidative stress, endothelial dysfunction and vascular inflammation

Abstract

BackgroundAircraft noise exposure is responsible for the emergence of oxidative stress, endothelial dysfunction and induction of vascular inflammatory response leading to cardiovascular complications like heart attacks and strokes. The AMP‐dependent‐Kinase (AMPK) has important protective roles in the vasculature especially in situations of oxidative stress and vascular inflammation. In the present study, we investigated the activation of AMPK using daily AICAR injections as a preventive strategy against noise induced destructive effects.Methods and ResultsAICAR (5‐Aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside; =AMP analog) was used for stimulation of AMPK activity and administered daily by intraperitoneal injections (200 mg/kg/day) for 7 days. After 3 days AICAR pre‐treatment, the C57BL/6j mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A)), which does not impair hearing significantly.We could show that aircraft noise exposure lead to a significant endothelial dysfunction, which was significantly improved by AMPK activation by AICAR. In addition, we observed that AICAR administration was able to normalize the aircraft noise induced blood pressure increment. Similarly, noise exposure induced oxidative stress as well as in whole blood samples was reduced by AICAR administration. Endothelial dysfunction and oxidative stress is often correlated with vascular inflammation processes. Induction of an inflammation (MCP‐1, PAI‐1, IL‐6) by aircraft noise exposure was abrogated using AICAR injection in the vasculature and brain. Furthermore, we could show that aircraft noise exposure induces circadian rhythm dysregulation, which can be reduced by AICAR administration.ConclusionWe here present novel data of AMPK activation with AICAR as a protective strategy against negative effects of aircraft noise exposure. Our data suggest that activation of AMPK might be a future therapeutic strategy to prevent traffic noise‐induced cardiovascular complications.Support or Funding InformationGerman Research Foundation ‐ Deutsche Forschungsgemeinschaft (DFG).