title: Variability in ozone-induced pulmonary injury and inflammation in healthy and cardiovascular-compromised rat models.
abstract: The molecular bases for variability in air pollutant-induced pulmonary injury due to underlying cardiovascular (CVD) and/or metabolic diseases are unknown. We hypothesized that healthy and genetic CVD-prone rat models will exhibit exacerbated response to acute ozone exposure dependent on the type and severity of disease. Healthy male 12-14-week-old Wistar Kyoto (WKY), Wistar (WS) and Sprague Dawley (SD); and CVD-compromised spontaneously hypertensive (SH), Fawn-Hooded hypertensive (FHH), stroke-prone spontaneously hypertensive (SHSP), obese spontaneously hypertensive heart failure (SHHF) and obese JCR (JCR) rats were exposed to 0.0, 0.25, 0.5, or 1.0 ppm ozone for 4 h; pulmonary injury and inflammation were analyzed immediately following (0-h) or 20-h later. Baseline bronchoalveolar lavage fluid (BALF) protein was higher in CVD strains except for FHH when compared to healthy. Ozone-induced increases in protein and inflammation were concentration-dependent within each strain but the degree of response varied from strain to strain and with time. Among healthy rats, SD were least affected. Among CVD strains, lean rats were more susceptible to protein leakage from ozone than obese rats. Ozone caused least neutrophilic inflammation in SH and SHHF while SHSP and FHH were most affected. BALF neutrophils and protein were poorly correlated when considering the entire dataset (r = 0.55). The baseline and ozone-induced increases in cytokine mRNA varied markedly between strains and did not correlate with inflammation. These data illustrate that the degree of ozone-induced lung injury/inflammation response is likely influenced by both genetic and physiological factors that govern the nature of cardiovascular compromise in CVD models.
authors.affiliation: a Environmental Public Health Division .
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
authors.affiliation: a Environmental Public Health Division .
authors.forename: Allen D
authors.initials: AD
authors.lastname: Ledbetter
authors.affiliation: a Environmental Public Health Division .
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Thomas
authors.affiliation: a Environmental Public Health Division .
authors.forename: Judy E
authors.initials: JE
authors.lastname: Richards
authors.affiliation: b Research Cores Unit, National Health and Environmental Effects Research Laboratory , and.
authors.forename: William O
authors.initials: WO
authors.lastname: Ward
authors.affiliation: a Environmental Public Health Division .
authors.forename: Mette C
authors.initials: MC
authors.lastname: Schladweiler
authors.affiliation: c National Program for Air Climate and Energy Research, U.S. Environmental Protection Agency , Research Triangle Park , NC , USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Costa
mesh_terms: D000393:Air Pollutants / Q000633:toxicity; D000818:Animals; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002318:Cardiovascular Diseases / Q000473:pathology*; D007249:Inflammation / Q000139:chemically induced*; D019570:Inhalation Exposure; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009504:Neutrophils; D010126:Ozone / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D010126:Ozone
keywords: Cardiovascular disease models; cytokine expression; inflammation; ozone; pulmonary injury; rat models