Submitted on September 27, 2007
Accepted on April 24, 2008
Exposure to Inhaled Particulate Matter Impairs Cardiac Function in Senescent Mice
Clarke G Tankersley1*, Hunter C. Champion2, Eiki Takimoto2, Kathleen L Gabrielson3, Djahida Bedja3, Vikas Misra1, Hazim El-Haddad2, Richard Rabold1, and Wayne Mitzner1
1 Department of Environmental Health Sciences, Johns Hopkins University, School of Public Health, Baltimore, Maryland, United States
2 Department of Cardiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States
3 Comparative Medicine, Johns Hopkins University, Baltimore, Maryland, United States
* To whom correspondence should be addressed. E-mail: ctankers{at}jhsph.edu.
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-month (mos) old mice at baseline and immediately following 3-hr exposures to either filtered air (FA) or carbon black (CB; ~400µg/m3) on four days. At 28-mos, 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-mos also demonstrate significant (P<0.05) reductions in ejection fraction and increases in right ventricular (RV) and pulmonary vascular pressures following CB exposure. Functional changes at 28-mos are associated with increased ROS production as suggested by enhanced luminol activity. This elevated ROS production with aging and CB exposure is attributable to nitric oxide synthase (NOS) uncoupling. Measurements of natriuretic peptide (ANP and BNP) 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.
