Prolonged exposure to noise pollution causes an increase in inflammatory signaling in the setting of hypertension

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Hypertension is the most important risk factor in the development of cardiovascular disease. The development of hypertension is multifactorial and determined by dietary, environmental, and genetic factors, complicating the characterization and treatment of the disease. We have previously established development of hypertension and an increase in inflammatory parameters following acute noise exposure [Münzel et al. Eur Heart J 2017; Kröller‐Schön et al. Eur Heart J 2018], a feature that were also observed in angiotensin II induced hypertension [Wenzel et al. Circulation 2011]. For the first time, we here aimed to characterize the effects of noise exposure and subsequent chronic stress in mice with pre‐established hypertension in order to determine the degree of overlap in the mechanistic pathways. In order to accomplish this, we treated C57Bl/6J mice for 7 days with angiotensin II, aircraft noise, or both. A cumulative worsening was evident in the hypertension plus noise group over hypertensive‐only and noise‐only controls. Expression of CD68, MCP‐1, VCAM‐1 and IL‐6 mRNA in the aorta showed an increase in chemoattraction as a consequence of noise exposure in hypertensive animals. A similar trend was seen in cortical tissue of the animals, where hypertensive noise‐exposed mice had the highest expression of IL‐1β and IL‐6 mRNA as well as heightened levels of astrocyte activation. Heightened levels of MCP‐1 and IL‐6 were confirmed on the protein level in aortic tissue via western blot analysis and dot blot analysis, respectively, indicating that noise exacerbates the inflammatory phenotype seen in hypertension systemically. FACS of aortic tissue of hypertensive noise‐exposed animals revealed an additional invasion of neutrophils, inflammatory monocytes, and T cells into the aorta upon noise exposure when compared to noise‐only and hypertension‐only controls. To identify the role of these inflammatory monocytes, LysMCre iDTR mice were injected for 10 days with diphtheria toxin, resulting in a specific ablation of LysM+ cells. These mice were mostly protected from the detrimental inflammatory effects induced by noise exposure, including VCAM‐1 expression in the aorta and also from the hypertension resulting thereupon, indicating monocytes have a critical role in the onset of noise‐induced hypertension.Support or Funding InformationThis work was supported by a vascular biology research grant from the Else‐Kröner‐Fresenius Foundation for “Noise and arterial hypertension” (2017_A106 to S.S.) and from the Boehringer Ingelheim Foundation for the collaborative research group ‘Novel and neglected cardiovascular risk factors: molecular mechanisms and therapeutic implications’ to study the effects of aircraft noise exposure on vascular function and oxidative stress (A.D., S.S., and T.M.). K.Fra. is recipient of a career development award of the Stavros Niarchos Foundation. T.M. is PI of the DZHK (German Center for Cardiovascular Research), Partner Site Rhine‐Main, Mainz, Germany