Exposure to inhaled particulate matter impairs cardiac function in senescent mice

Clarke G. Tankersley, Hunter C. Champion, Eiki Takimoto, Kathleen Gabrielson, Djahida Bedja, Vikas Misra, Hazim El-Haddad, Richard Rabold, Wayne Mitzner

Research output: Contribution to journalArticle

31 Citations (Scopus)

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; ∼400 μg/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.

Original languageEnglish
Pages (from-to)R252-R263
Number of pages12
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume295
Issue number1
DOIs
Publication statusPublished - Jul 2008
Externally publishedYes

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