Cardiovascular Depression in Rats Exposed to Inhaled Particulate Matter and Ozone: Effects of Diet-Induced Metabolic Syndrome

Abstract

Background: High ambient levels of ozone (O3) and fine particulate matter (PM2.5) are associated with cardiovascular morbidity and mortality, especially in people with preexisting cardiopulmonary diseases. Enhanced susceptibility to the toxicity of air pollutants may include individuals with metabolic syndrome (MetS).Objective: We tested the hypothesis that cardiovascular responses to O3 and PM2.5 will be enhanced in rats with diet-induced MetS.Methods: Male Sprague-Dawley rats were fed a high-fructose diet (HFrD) to induce MetS and then exposed to O3, concentrated ambient PM2.5, or the combination of O3 plus PM2.5 for 9 days. Data related to heart rate (HR), HR variability (HRV), and blood pressure (BP) were collected.Results: Consistent with MetS, HFrD rats were hypertensive and insulin resistant, and had elevated fasting levels of blood glucose and triglycerides. Decreases in HR and BP, which were found in all exposure groups, were greater and more persistent in HFrD rats compared with those fed a normal diet (ND). Coexposure to O3 plus PM2.5 induced acute drops in HR and BP in all rats, but only ND rats adapted after 2 days. HFrD rats had little exposure-related changes in HRV, whereas ND rats had increased HRV during O3 exposure, modest decreases with PM2.5, and dramatic decreases during O3 plus PM2.5 coexposures.Conclusions: Cardiovascular depression in O3- and PM2.5-exposed rats was enhanced and prolonged in rats with HFrD-induced MetS. These results in rodents suggest that people with MetS may be prone to similar exaggerated BP and HR responses to inhaled air pollutants.Citation: Wagner JG, Allen K, Yang HY, Nan B, Morishita M, Mukherjee B, Dvonch JT, Spino C, Fink GD, Rajagopalan S, Sun Q, Brook RD, Harkema JR. 2014. Cardiovascular depression in rats exposed to inhaled particulate matter and ozone: effects of diet-induced metabolic syndrome. Environ Health Perspect 122:27–33; http://dx.doi.org/10.1289/ehp.1307085

Long‐Term Exposure of Fine Particulate Matter Causes Hypertension by Impaired Renal D 1 Receptor–Mediated Sodium Excretion via Upregulation of G‐Protein–Coupled Receptor Kinase Type 4 Expression in Sprague‐Dawley Rats

“…Epidemiological studies have shown that traffic or household PM 2.5 exposure can increase blood pressure in both the short‐ and long‐term. Many animal experimental studies have validated the view of the above‐mentioned evidence‐based‐studies . In this study, PM 2.5 was confirmed to be associated with increased blood pressure, and the blood pressure was positively correlated with the exposure dose within a certain range.…”

“…Many animal experimental studies have validated the view of the above-mentioned evidence-based-studies. 8,31,[52][53][54] In this study, PM 2.5 was confirmed to be associated with increased blood pressure, and the blood pressure was positively correlated with the exposure dose within a certain range. Even a lower concentration of PM 2.5 exposure can cause an increased blood pressure.…”

Repeated ozone exposure exacerbates insulin resistance and activates innate immune response in genetically susceptible mice

“…Mice (8/group) were exposed to filtered air (FA), or O 3 (O 3 ; 0.5 ppm target) for 13 consecutive weekdays (Monday to Friday, 4 h/day). Choice of the O 3 exposure regimen was made on previously reported rodent studies in our group and others (Katre et al 2011; Last et al 2004; Sun et al 2013; Wagner et al 2014; Ying et al 2016). The magnitude of O 3 -induced airway epithelial injury and inflammation are exposure (e.g., concentration, time, and frequency) and species dependent.…”

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

“…A number of mechanistic pathways have been proposed where lung injury/inflammation initiates systemic inflammation, which is postulated to play a central role in inhaled pollutant-induced insulin resistance, but the evidence remains insufficient (Shoelson et al, 2006; O’Neill et al, 2007; Xu et al, 2011; Yan et al, 2011; Rajagopalan and Brook, 2012). Similar to PM, the ubiquitous air pollutant ozone (O 3 ) has been associated with adverse pulmonary and cardiovascular health effects, such as lung injury/inflammation, decreased lung function and heart rate variability in animals and humans (Watkinson et al, 2001; Hollingsworth et al, 2007; Ciencewicki et al, 2008; Liu et al, 2009; Farraj et al, 2012; Wagner et al, 2014). However, the likely contribution of O 3 to metabolic disorder and extra-pulmonary effects has yet to be systematically investigated.…”