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Hypoxia Stress Test Reveals Exaggerated Cardiovascular Effects in Hypertensive Rats after Exposure to the Air Pollutant Acrolein
Citation:
Perez, C., A. Ledbetter, M. Hazari, N. Coates, A. Carll, D. Winsett, D. Costa, AND A. Farraj. Hypoxia Stress Test Reveals Exaggerated Cardiovascular Effects in Hypertensive Rats after Exposure to the Air Pollutant Acrolein. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 132(2):467-77, (2013).
Impact/Purpose:
These findings highlight the utility of a hypoxia stress test as a tool to unmask the potential for latent effects of air pollution and associated mechanisms (e.g., altered autonomic tone) that mediate cardiovascular dysfunction. The results further show that pre-existing cardiovascular disease confers exaggerated sensitivity to the effects of a model irritant, acrolein, that are consistent with epidemiological findings showing “delayed or latent” outcomes of air pollutant exposures. These findings may help reduce uncertainty in standard setting by providing more sensitive methods that reveal health effects at ambient concentrations as reported in the epidemiological literature and by establishing biological plausibility for health effects.
Description:
Exposure to air pollution increases the risk of cardiovascular morbidity and mortality, especially in susceptible populations with cardiovascular disease. Stress tests are useful in assessing cardiovascular risk and manifesting latent effects of exposure. The goal of this study was to use a hypoxia stress test to elucidate susceptibility to environmental pollutants in a rodent model of hypertension. We hypothesized that exposure to acrolein, a potent environmental pollutant and pulmonary irritant, would increase cardiopulmonary sensitivity to hypoxia, particularly in hypertensive rats. Spontaneously hypertensive (SH) and Wistar Kyoto (WKY; normotensive) rats, implanted with biopotential radiotelemetry transmitters were exposed once for 3 hours to 3 ppm acrolein gas or filtered air in whole body plethysmograph chambers and challenged with a 10% oxygen atmosphere (10 minutes) 24 hours later. Cardiovascular and ventilatory parameters were monitored during acrolein and hypoxia exposures. Acrolein exposure caused significant increases in heart rate, blood pressure, breathing frequency, and minute volume in the hypertensive rat that were coupled with significant increases in the heart rate variability parameter LF, suggesting a potential role for increased sympathetic tone. There were little to no effects in the normotensive rat during acrolein exposure. The hypoxia stress test performed after acrolein exposure revealed increased diastolic blood pressure only in the hypertensive rat and increased minute volume and expiratory time only in normotensive rats. These results suggest that hypertension confers exaggerated sensitivity to air pollution and that the hypoxia stress test may be a useful tool to reveal the potential latent effects of air pollution exposure.