title: Exposure to inhaled particulate matter impairs cardiac function in senescent mice.
abstract: Daily exposure to particulate matter (PM) is known to adversely affect cardiac function and is also known to be exaggerated with senescence. This study tests the hypothesis that cardiac function is uniquely altered by PM exposure in senescent mice. A mechanism for PM-induced cardiac effects is also postulated by examining the activity of nitric oxide synthase (NOS) and the generation of reactive oxygen species (ROS) in heart tissue. Echocardiography is performed in awake 18- and 28-mo-old mice at baseline and immediately following 3-h exposures to either filtered air or carbon black (CB; approximately 400 microg/m3) on 4 days. At 28 mo, left ventricular diameter at end-systole and end-diastole is significantly (P < 0.05) elevated, and fractional shortening is significantly reduced (49 +/- 3% vs. 56 +/- 3%) with CB exposure. In vivo hemodynamic measurements at 28 mo also demonstrate significant (P < 0.05) reductions in ejection fraction and increases in right ventricular and pulmonary vascular pressures following CB exposure. Functional changes at 28 mo are associated with increased ROS production as suggested by enhanced luminol activity. This elevated ROS production with aging and CB exposure is attributable to NOS uncoupling. Measurements of natriuretic peptide (atrial and brain) transcription and matrix metalloproteinase (MMP2 and MMP9) activity in heart tissue are significantly (P < 0.05) amplified with senescence and exposure to CB, pointing to increased cardiac stress and remodeling. These results demonstrate that acute PM exposure reduces cardiac contractility in senescent mice, and this decline in function is associated with increased ROS production linked to NOS uncoupling.
authors.affiliation: Department of Environmental Health Sciences, Bloomberg School of Public Health and School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: Clarke G
authors.initials: CG
authors.lastname: Tankersley
authors.forename: Hunter C
authors.initials: HC
authors.lastname: Champion
authors.forename: Eiki
authors.initials: E
authors.lastname: Takimoto
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gabrielson
authors.forename: Djahida
authors.initials: D
authors.lastname: Bedja
authors.forename: Vikas
authors.initials: V
authors.lastname: Misra
authors.forename: Hazim
authors.initials: H
authors.lastname: El-Haddad
authors.forename: Richard
authors.initials: R
authors.lastname: Rabold
authors.forename: Wayne
authors.initials: W
authors.lastname: Mitzner
mesh_terms: D000280:Administration, Inhalation; D000375:Aging; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004452:Echocardiography; D004781:Environmental Exposure; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052638:Particulate Matter / Q000009:adverse effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015203:Reproducibility of Results; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors
chemical_list: D052638:Particulate Matter; D017382:Reactive Oxygen Species; D001708:Biopterins; D019001:Nitric Oxide Synthase; C003402:sapropterin