Airway Exposure to Environmental Allergens Increases Blood Pressure and Alters Responsiveness to Ozone and Arrhythmogenic Challenge in Rats
Citation:
Farraj, A., B. Martin, J. Dye, Mette C. Schladweiler, W. Williams, C. Miller, Abdul Malek Khan, J. Richards, W. Martin, A. Henriquez, R. Grindstaff, S. Gavett, Ian Gilmour, U. Kodavanti, AND M. Hazari. Airway Exposure to Environmental Allergens Increases Blood Pressure and Alters Responsiveness to Ozone and Arrhythmogenic Challenge in Rats. Annual Meeting of the Society of Toxicology, Virtual, March 14 - 18, 2021.
Impact/Purpose:
This study examined the cardiovascular impacts of exposure to an environmental allergen mixture. The findings presented in this abstract show for the first time that in the setting of experimental allergic airways disease elicited by common human environmental allergens, cardiovascular function is altered. These findings reveal evidence in an experimental model that 1) is consistent with and supports epidemiological findings that associate asthma with increased cardiovascular risk and 2) point to functional changes and perhaps changes in cardiac electrical function that may allude to mechanistic underpinnings responsible for increased risk. Furthermore, allergic airways disease modifies responses to ozone. Such findings may increase our understanding of the cardiovascular vulnerability of asthmatics overall and effect modification by exposure to air pollution.
Description:
Asthma and allergic rhinitis result from the interplay of genetic determinants and exposure to inhaled environmental triggers. While the respiratory impacts of allergic airways disease have been well-studied, the burden on the cardiovascular system has received comparatively little attention. Importantly, epidemiological studies have demonstrated that asthma increases risk for stroke and coronary heart disease. The precise cardiovascular risks associated with allergic airways disease and the biological mechanisms responsible, however, remain unknown. The purpose of this study was to determine the impacts of allergic airways disease on cardiovascular function in an experimental model. Female rats were intranasally instilled for 6 weeks with saline or a mixture of environmental allergens (i.e. house dust mite, aspergillus fumigatus, and ragweed) previously shown to elicit allergic airways disease. Rats were then exposed once to 0.5 ppm ozone to assess cardiovascular sensitivity to a prototypical air pollutant. Cardiovascular function, including blood pressure (BP) and the electrocardiogram, was constantly monitored using implantable telemetry. Sensitivity to the cardiac arrhythmogenic agent aconitine was also assessed. The allergen mixture caused an increase in bronchioalveolar lavage fluid (BALF) eosinophils and lymphocytes and the cytokines interleukin (IL)-4 and IL-5, among others, characteristic of allergic airways disease. Moreover, allergen treatment also increased diastolic BP and sensitivity to aconitine-induced cardiac arrhythmia. Finally, ozone decreased heart rate in both saline and allergen-instilled groups and increased BALF IL-13, interferon-gamma and keratinocyte chemoattractant/growth-regulated oncogene exposure only in allergen-instilled rats. These findings demonstrate that allergic airways disease may increase cardiovascular risk in part by altering blood pressure and by causing cardiac electrical instability (This abstract does not reflect U.S. E.P.A policy).