title: Cardiopulmonary responses of Wistar Kyoto, spontaneously hypertensive, and stroke-prone spontaneously hypertensive rats to particulate matter (PM) exposure.
abstract: Humans with underlying cardiovascular disease, including stroke, are more susceptible to ambient particulate matter (PM)-induced morbidity and mortality. We hypothesized that stroke-prone spontaneously hypertensive rats (SHRSP) would be more susceptible than healthy Wistar Kyoto (WKY) rats to PM-induced cardiac oxidative stress and pulmonary injury. We further postulated that PM-induced injury would be greater in SHRSP than in spontaneously hypertensive rats (SHR) based on the greater disease severity in SHRSP than SHR. First, male WKY and SHRSP were intratracheally (IT) instilled with saline or 1.11, 3.33, or 8.33 mg/kg of oil combustion PM and responses were analyzed 4 or 24 h later. Second, SHR and SHRSP were IT instilled with saline or 3.33 or 8.33 mg/kg of the same PM and responses were analyzed 24 h later. Pulmonary injury and inflammation were assessed in bronchoalveolar lavage fluid (BALF) and cardiac markers in cytosolic and mitochondrial fractions. BALF neutrophilic inflammatory response was induced similarly in all strains following PM exposure. BALF protein leakage, gamma-glutamyl transferase, and N-acetylglucosaminidase activities, but not lactate dehydrogenase activity, were exacerbated in SHRSP compared to WKY or SHR. Pulmonary cytosolic and cardiac mitochondrial ferritin levels decreased, and cardiac cytosolic superoxide dismutase (SOD) activity increased in SHRSP only. Pulmonary SOD activity decreased in WKY and SHRSP. Cardiac mitochondrial isocitrate dehydrogenase (ICDH) activity decreased in PM-exposed WKY and SHR; control levels were lower in SHRSP than SHR or WKY. In summary, strain-related differences exist in pulmonary protein leakage and oxidative stress markers. PM-induced changes in cardiac oxidative stress sensitive enzymes are small, and appear only slightly exacerbated in SHRSP compared to WKY or SHR. Multiple biological markers may be differentially affected by PM in genetic models of cardiovascular diseases. Preexisting cardiovascular disease may influence susceptibility to PM pulmonary and cardiac health effects in a disease-specific manner.
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina School of Public Health, Chapel Hill, North Carolina, USA.
authors.forename: J Grace
authors.initials: JG
authors.lastname: Wallenborn
authors.forename: Mette C
authors.initials: MC
authors.lastname: Schladweiler
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
authors.forename: Jo Anne
authors.initials: JA
authors.lastname: Johnson
authors.forename: Ronald
authors.initials: R
authors.lastname: Thomas
authors.forename: Richard H
authors.initials: RH
authors.lastname: Jaskot
authors.forename: Judy H
authors.initials: JH
authors.lastname: Richards
authors.forename: Allen D
authors.initials: AD
authors.lastname: Ledbetter
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000393:Air Pollutants / Q000633:toxicity*; D000418:Albumins / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005293:Ferritins / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D052638:Particulate Matter / Q000633:toxicity*; D011210:Power Plants; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke; D013482:Superoxide Dismutase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D000418:Albumins; D052638:Particulate Matter; D005293:Ferritins; D007770:L-Lactate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D013482:Superoxide Dismutase; D005969:Glutamate Dehydrogenase; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase