title: Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure.
abstract: Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. However, cross-model organ pathologies and clinical manifestations are often not compared. We hypothesized that genetic CVD rat models will exhibit baseline pathologies and will thus express varied lung response to acute ozone exposure. Male 12-14-week-old healthy Wistar Kyoto (WKY), Wistar (WIS), and Sprague-Dawley (SD) rats and CVD-compromised spontaneously hypertensive (SH), fawn-hooded hypertensive (FHH), stroke-prone SH (SHSP), obese SH heart-failure (SHHF), obese diabetic JCR (JCR) rats were exposed to 0.0, 0.25, 0.5, or 1.0 ppm ozone for 4 h and clinical biomarkers, and lung, heart and kidney pathologies were compared immediately following (0-h) or 20-h later. Strain differences were observed between air-exposed CVD-prone and WKY rats in clinical biomarkers and in kidney and heart pathology. Serum cholesterol was higher in air-exposed obese SHHF and JCR compared to other air-exposed strains. Ozone did not produce lesions in the heart or kidney. CVD-prone and SD rats demonstrated glomerulopathy and kidney inflammation (WKY = WIS = SH < SD = SHSP < SHHF < JCR = FHH) regardless of ozone. Cardiac myofiber degeneration was evident in SH, SHHF, and JCR, while only JCR tends to have inflammation in coronaries. Lung pathology in air-exposed rats was minimal in all strains except JCR. Ozone induced variable alveolar histiocytosis and bronchiolar inflammation; JCR and SHHF were less affected. This study provides a comparative account of the clinical manifestations of disease and early-life organ pathologies in several rat models of CVD and their differential susceptibility to lung injury from air pollutant exposure.
authors.affiliation: a Hadassah - Hebrew University Medical Center , Jerusalem , Israel .
authors.forename: Yuval
authors.initials: Y
authors.lastname: Ramot
authors.affiliation: b Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park , NC , USA .
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
authors.affiliation: c NIEHS/NIH , Research Triangle Park , NC , USA , and.
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
authors.affiliation: b Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park , NC , USA .
authors.forename: Allen D
authors.initials: AD
authors.lastname: Ledbetter
authors.affiliation: d Department of Pathology , Tel Aviv University , Tel Aviv , Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
mesh_terms: D000393:Air Pollutants / Q000633:toxicity; D000818:Animals; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006331:Heart Diseases / Q000139:chemically induced; D015614:Histiocytosis / Q000139:chemically induced*; D007249:Inflammation / Q000139:chemically induced*; D019570:Inhalation Exposure; D007674:Kidney Diseases / Q000139:chemically induced; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000393:Air Pollutants; D010126:Ozone
keywords: Cardiovascular disease models; clinical biomarkers; kidney; ozone; pathology; rat models