α1AMPK as a target of preventive strategies against aircraft noise induced (vascular) stress:aircraft noise induced cardiovascular complications – pharmacological (metformin) and non-pharmacological (physical exercise and fasting) α1AMPK mediated interven

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Noise as an environmental risk factor and its effects on humans are coming more and more into the focus of scientific interest. The WHO estimates a loss of one million healthy life years due to environmental noise exposure supported by several epidemiological studies. Our group could show that nighttime noise exposure of healthy adults not only lead to a disruption of sleep rhythm but also increased blood pressure, pulse and levels of stress hormones There are almost no animal model systems to study the vascular consequences of noise although there are a lot of analyses focusing on the effects of noise on the behavior pattern, fertility and production of milk etc. in farm animals. We could only find three publications on the effects of noise exposure of animals on cardiovascular function using noise exposure protocols high sound pressure levels (≥100 dBA). Most likely this will lead to an auditory damage of the animals’ cochlea. Based on these previous studies our group developed a noise exposure model with lower peak sound levels (<85 dBA), lower mean sound pressure levels (72 dBA).The AMP-dependent protein kinase (AMPK) is a ubiquitously expressed enzyme which acts as an energy sensor since the ratio between AMP and ATP determines its activity. In the cardiovascular system AMPK in known to activate the NO generating enzyme eNOS and is promoting angiogenesis. Our group could show that the vascular isoform is able to inhibit sources of vascular oxidative stress to maintain endothelial function. The pharmacological activation of AMPK with AICAR lead to an improvement of angiotensin II induced vascular dysfunction and oxidative stress. Furthermore AMPK plays an important role mediating protective effects of exercise training on the vascular system. Although the beneficial effects of exercise training on the cardiovascular risk are known there is a social trend towards less physical activity. An alternative to physical exertion would be intermittent fasting or caloric restriction, which shows a clear correlation with less cardiovascular events supported by epidemiological studies. The here mentioned lifestyle (exercise training, fasting or caloric restriction) show beneficial effects on the cardiovascular system which are mostly AMPK dependent. Therefore, the major aims of the current proposal are to study if these strategies can be used to reduce noise-induced vascular stress.