Acrolein inhalation alters arterial blood gases and triggers carotid body-mediated cardiovascular responses in hypertensive rats

• Published in: Inhalation toxicology 2015-01, Vol.27 (1), p.54-63
• Main Authors: Perez, Christina M., Hazari, Mehdi S., Ledbetter, Allen D., Haykal-Coates, Najwa, Carll, Alex P., Cascio, Wayne E., Winsett, Darrell W., Costa, Daniel L., Farraj, Aimen K.
• Format: Article
• Language: English
• Subjects: Acrolein; Acrolein - toxicity; Alkynes - pharmacology; Animals; Blood Gas Analysis; blood pressure; carotid body; Carotid Body - physiology; Cystathionine gamma-Lyase - antagonists & inhibitors; Glycine - analogs & derivatives; Glycine - pharmacology; Heart Rate - drug effects; Hypertension - physiopathology; Male; Rats, Inbred SHR; Rats, Inbred WKY; spontaneously hypertensive rat; Ventricular Pressure - drug effects
• ISSN: 0895-8378; 1091-7691
• DOI: 10.3109/08958378.2014.984881

Abstract Context: Air pollution exposure affects autonomic function, heart rate, blood pressure and left ventricular function. While the mechanism for these effects is uncertain, several studies have reported that air pollution exposure modifies activity of the carotid body, the major organ that senses changes in arterial oxygen and carbon dioxide levels, and elicits downstream changes in autonomic control and cardiac function. Objective: We hypothesized that exposure to acrolein, an unsaturated aldehyde and mucosal irritant found in cigarette smoke and diesel exhaust, would activate the carotid body chemoreceptor response and lead to secondary cardiovascular responses in rats. Materials and methods: Spontaneously hypertensive (SH) rats were exposed once for 3 h to 3 ppm acrolein gas or filtered air in whole body plethysmograph chambers. To determine if the carotid body mediated acrolein-induced cardiovascular responses, rats were pretreated with an inhibitor of cystathionine γ-lyase (CSE), an enzyme essential for carotid body signal transduction. Results: Acrolein exposure induced several cardiovascular effects. Systolic, diastolic and mean arterial blood pressure increased during exposure, while cardiac contractility decreased 1 day after exposure. The cardiovascular effects were associated with decreases in pO2, breathing frequency and expiratory time, and increases in sympathetic tone during exposure followed by parasympathetic dominance after exposure. The CSE inhibitor prevented the cardiovascular effects of acrolein exposure. Discussion and conclusion: Pretreatment with the CSE inhibitor prevented the cardiovascular effects of acrolein, suggesting that the cardiovascular responses with acrolein may be mediated by carotid body-triggered changes in autonomic tone. (This abstract does not reflect EPA policy.)