| Diesel exhaust (DE) is a major contributor to traffic-related urban air pollution and has been associated with cardiovascular dysfunction in humans, especially susceptible individuals. DE is a complex pollutant consisting of particles and toxic gases such as acrolein. Although the mechanisms that mediate adverse cardiovascular health effects are unclear, epidemiological evidence has linked exposure to air pollution to drops in blood oxygen saturation, suggesting that hypoxia may play a role. Acute and repeated hypoxia is associated with carotid body-mediated cardiovascular effects which overtime lead to hypertension and predisposition to cardiac arrhythmia. Thus, my overarching hypothesis for this dissertation project is that air pollutant-induced hypoxia mediates the adverse cardiovascular effects of air pollution exposure. To test this hypothesis, we 1) characterized the impacts of short-term exposure to DE on cardiovascular physiology in rats, 2) characterized the cardiovascular response to exposure to the DE component acrolein, and determined if acrolein exposure increases the risk of adverse cardiovascular responses to a cardiac stressor (i.e, hypoxic atmosphere) in hypertensive rats, and 3) determined if inhibition of the sensory response to hypoxia attenuated air-pollutant-induced cardiovascular dysfunction. Exposure to DE caused PR prolongation and ST depression, a marker of myocardial ischemia, only in hypertensive rats exposed to the gaseous components of DE. Because the gaseous components appeared to be driving the responses, studies were conducted to assess the effects of acrolein. Exposure to acrolein caused increases in heart rate and blood pressure. These responses were confined to the hypertensive rat, and subsequent stress testing with hypoxic atmosphere (10% FiO2) confirmed enhanced sensitivity with increased diastolic blood pressure in the hypertensive rat. We also found that acrolein exposure significantly decreased arterial pO2, and carotid body inhibition prevented acrolein-induced blood pressure increases and impaired contractility responses in hypertensive rats. This suggests that air pollutants may cause hypoxia and that the cardiac responses following pollutant exposure may be mediated by the carotid body. This research describes a novel mechanism that mediates the adverse cardiovascular effects of air pollutant exposure and fills important data gaps in our understanding of air pollution-induced cardiovascular dysfunction. |
