Cardiovascular and Systemic Responses to Inhaled Pollutants in Rodents: Effects of Ozone and Particulate Matter

Abstract

539Over the past decade our laboratory has been investigating the nature and extent of specific extrapulmonary responses observed in rodents following exposure to ambient pollutants and other xenobiotic agents. These responses are characterized by primary decreases in important indices of cardiac and thermoregulatory functions, along with secondary decreases in associated parameters. The summation of these effects, termed the hypothermic response (1), has both physiological and behavioral components, appears to be most pronounced in (and possibly unique to) the rodent, and may significantly impact the interpretation of experimental data and its subsequent extrapolation to the human situation. Typically, healthy adult rats may exhibit decreases in heart rate (HR) of 50-100 beats per minute (bpm) and decreases in core temperature (T co ) of 1.5-2.5°C following routine exposures to moderate levels of ambient pollutants, such as ozone (O 3 ) or particulate matter (PM). In addition, there appear to be similar, albeit related, decreases in other functional parameters, including metabolism, minute ventilation, blood pressure, and cardiac output. Furthermore, it has been demonstrated that the magnitudes of these observed decreases may be significantly modulated by changes in experimental conditions. For example, experimental stresses related to exercise, restraint, and handling, as well as the imposition of changes in ambient temperature (T a ), have all been shown to have profound effects on these responses. Finally, it has been proposed that a moderate hypothermic response may afford protection and improve survivability following toxic exposures, whereas a more severe response may actually potentiate the toxicity. Although the underlying mechanisms of the hypothermic response are still largely unexplored and unknown, preliminary experimental evidence suggests that these effects may be mediated, at least partly, via components of the parasympathetic nervous system. O 3 is a ubiquitous ambient pollutant and a known pulmonary irritant (2). In a series of earlier studies from our laboratory (3-6), we investigated both the pulmonary and systemic consequences of O 3 exposures (0.25-2.0 ppm) in rodents. With respect to nonpulmonary end points, these studies used radiotelemetry procedures to examine HR, T co , and electrocardiographic changes in rats and mice over a variety of experimental conditions. These studies were among the first to report consistent, robust concentration-related decreases in the abovementioned parameters in rodents following exposure to routine experimental levels of O 3 .More recently, the putative toxicity of PM has attracted considerable attention, and numerous epidemiological studies published over the last few years have reported a slight but consistent association between the concentration of ambient PM and the incidence of adverse health effects in man (7-12). Despite limited supporting experimental evidence, there is a growing consensus that higher levels of PM in the air are associated with in...

Stress and Hypothermia in Mice in A Nose-Only Cigarette Smoke Exposure System

“…This has previously been observed in rats (Altland et al, 1978) and is in accordance with observations on the hypothermic effects of inhalation of carbon monoxide and/or nicotine (Altland & Rattner, 1979;Lopez et al, 2003). In fact, inhalation of a wide range of xenobiotic substances such as ozone, acrylates, and formaldehyde (Watkinson et al, 2001;Jaeger & Gearhart, 1982;Silver et al, 1981) elicits a hypothermic response in rodents. The magnitude of this response is determined by the concentration of the xenobiotic, the mass of the animal, and environmental stress associated with, for example, restraint (Watkinson et al, 2003).…”

Health Effects of Fine Particulate Air Pollution: Lines that Connect

“…Several animal studies have also observed PM exposure-related changes in cardiac rhythm or function. 326,[397][398][399] There is evidence that PM-related changes in cardiac autonomic function are not independent of pathways that involve pulmonary and systemic oxidative stress. Schwartz et al 308 provide evidence that the PM 2.5 associations with HRV (the high-frequency component) are at least partially mediated by reactive oxygen species.…”

Effects of concentrated ambient particles on heart rate and blood pressure in pulmonary hypertensive rats.

“…Preliminary studies revealed increased heart rates and arrhythmia in pulmonary hypertensive rats after exposure to concentrated ambient particles (8,10,11). However, a recent study revealed a decreased heart rate when residual oil fly ash was instilled into the rats (12). To investigate further the mechanisms of particleinduced cardiotoxicity, we used heart rate and blood pressure as outcome indicators to assess their association with concentrated ambient particles in pulmonary hypertensive rats.…”