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Acrolein Inhalation Alters Arterial Blood Gases and Triggers Carotid Body Mediated Cardiovascular Responses in Hypertensive Rats
Citation:
Perez, C., M. Hazari, A. Ledbetter, N. Coates, A. Carll, D. Winsett, D. Costa, AND A. Farraj. Acrolein Inhalation Alters Arterial Blood Gases and Triggers Carotid Body Mediated Cardiovascular Responses in Hypertensive Rats. INHALATION TOXICOLOGY. Informa Healthcare USA, New York, NY, 1:54-63, (2015).
Impact/Purpose:
This manuscript presents previously undescribed findings with respect to the health effects of air pollution. Prinicipal among them is the acrolein-induced increase in arterial blood pCO2 and decrease in pO2. These changes in blood gases were associated with cardiovascular responses that were prevented via inhibition of the carotid body. These findings establish biological plausibility for the epidemiological findings linking air pollution exposure to adverse health effects and provide insight on potential mechanisms of action.
Description:
Exposure to air pollution increases risk of cardiovascular morbidity and mortality, especially in individuals with underlying cardiopulmonary disease. While the mechanisms accounting for these effects are unclear, several epidemiological studies have reported decreases in oxygen saturation following exposure to air pollution. These findings suggest that systemic hypoxia may play a role in the initiation of some of the adverse cardiovascular effects associated with exposure to air pollution. We hypothesized that exposure to the air pollutant acrolein, would decrease blood oxygen levels and trigger carotid body mediated cardiovascular effects. Spontaneously Hypertensive (SH) rats were exposed once for three hours to 3 ppm acrolein gas or filtered air in whole body plethysmograph chambers. Blood pressure, heart rate, electrocardiogram and ventilatory parameters were measured. To determine the role of the carotid body, rats were pretreated with an inhibitor of cystathionine γ-lyase (CSE), an H2S-generating enzyme essential for carotid body signal transduction. A second identical cohort underwent arterial blood gas analysis before, during, and after acrolein exposure. In a third cohort, left ventricular pressure, cardiac contractility, and lusitropy were assessed before and after vagotomy one day after acrolein exposure. Acrolein significantly decreased pO2, breathing frequency, expiratory time, and cardiac contractility and significantly increased pCO2, body temperature and means arterial, systolic, and diastolic blood pressures. These effects were associated with increases in sympathetic tone (reduced heart rate variability) during exposure followed by parasympathetic dominance after exposure. Pretreatment with the CSE inhibitor prevented the cardiovascular effects of acrolein. These results suggest that acrolein-induced cardiac events may be mediated by the carotid body (This abstract does not reflect EPA policy).
