Episodic ozone exposure in adult and senescent Brown Norway rats: acute and delayed effect on heart rate, core temperature and motor activity

Abstract

Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O₃) is more reflective of potential exposures occurring in human populations and could be more harmful to the aged. This study used radiotelemetry to monitor heart rate (HR), core temperature (T(c)) and motor activity (MA) in adult (9-12 months) and senescent (20-24 months) male, Brown Norway rats exposed to episodic O₃ (6 h/day of 1 ppm O₃ for 2 consecutive days/week for 13 weeks). Acute O₃ initially led to marked drops in HR and T(c). As exposures progressed each week, there was diminution in the hypothermic and bradycardic effects of O₃. Senescent rats were less affected than adults. Acute responses were exacerbated on the second day of O₃ exposure with adults exhibiting greater sensitivity. During recovery following 2 d of O₃, adult and senescent rats exhibited an elevated T(c) and HR during the day but not at night, an effect that persisted for at least 48 h after O₃ exposure. MA was elevated in adults but not senescent rats during recovery from O₃. Overall, acute effects of O₃, including reductions in HR and T(c), were attenuated in senescent rats. Autonomic responses during recovery, included an elevation in T(c) with a pattern akin to that of a fever and rise in HR that were independent of age. An attenuated inflammatory response to O₃ in senescent rats may explain the relatively heightened physiological response to O₃ in younger rats.

Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

“…In nonexercising rats, acute ozone exposure induces glucose intolerance and increases circulating leptin and epinephrine (19,20). Both leptin and epinephrine changes are associated with a reversible decrease in body temperature (23), suggesting involvement of the sympathetic axis and changes in hypothalamic thermoregulation. Increased corticotropin and cortisol levels after ozone exposure have also been noted in other rodent studies (21,32).…”

“…Acute ozone exposure can increase levels of circulating stress hormones, such as epinephrine and corticosterone, in rats (19)(20)(21). Ozone exposure also induces cardiac autonomic effects in humans (22); hypothermia and bradycardia in rats (23); and leptinemia, hyperglycemia, glucose intolerance, and global changes in circulating metabolites involved in peripheral glucose, lipid, and amino acid metabolism in rats (20). These changes are reflective of classical stress response-mediated homeostatic alterations involving activation of sympathetic neurons and hypothalamus-pituitary-adrenal (HPA) axis (20).…”

Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats

“…Exposure to O 3 has also been shown to induce cardiovascular functional changes through modulation of the autonomic nervous system, which regulates sympathetic and parasympathetic balance (Farraj et al, 2012; Gordon et al, 2014). More specifically, acute O 3 exposure has been shown to stimulate lung vagal C-fibers through transient receptor potential member A1 (TRPA-1) receptors that lead to activation of neural stress-responsive regions in the central nervous system where lung afferents of vagus nerves terminate (Taylor-Clark and Undem, 2010; Gackiere et al, 2011).…”

Air Pollution and Insulin Resistance: Do All Roads Lead to Rome?

“…Rats have a reversible decrease in body temperature when exposed to ozone (6,7). This is associated with impaired glucose homeostasis (8) and mobilization of energy sources during stress responses, an observation that might coincide with the adaptive insulin resistance in peripheral tissues (9) that was observed in the new work by Vella et al (5).…”

“…However, highconcentration ozone exposure, especially during the night and in experiments of exceedingly long duration (16 h), which has been shown to cause remarkable lung injury in rats, is not likely to occur in a real-world scenario for humans. Moreover, we are still far from understanding if transient insulin resistance can be exacerbated or if adaptation is likely over extended periods, as noted with other biological end points on repeated chronic episodic ozone exposure (7,8). Considering the magnitude of the health burden of air pollution on chronic neurological and cardiovascular disease, lipidemia, ectopic lipid accumulation, nonalcoholic steatohepatitis, and diabetes in healthy and genetically compromised individuals, more studies like that by Vella et al (5) are needed to fully understand the impact of this exposure on chronic disease.…”