Variation in echocardiographic and cardiac hemodynamic effects of PM and ozone inhalation exposure in strains related to Nppa and Npr1 gene knock-out mice

Abstract

Elevated levels of ambient co-pollutants are associated with adverse cardiovascular outcomes shown by epidemiology studies. The role of particulate matter (PM) and ozone (O₃) as co-pollutants in this association is unclear. We hypothesize that cardiac function following PM and O₃ exposure is variably affected by genetic determinants (Nppa and Npr1 genes) and age. Heart function was measured before and after 2 days each of the following exposure sequence; (1) 2-h filtered air (FA) and 3-h carbon black (CB; 0.5 µg/m³); (2) 2-h O₃ (0.6 ppm) and 3-h FA; (3) 5-h FA; and, (4) 2-h O₃ and 3-h CB. Two age groups (5 and 18 months old (mo)) were tested in C57Bl/6J (B6) and 129S1/SvImJ (129) mice using echocardiographic (echo) and in vivo hemodynamic (IVH) measurements. With echo, posterior wall thickness was significantly (P < 0.01) greater in 129 relative to B6 mice at baseline. With CB exposure, young B6 and older 129 mice show significant (P < 0.01) reductions in fractional shortening (FS) compared to FA. With O₃ exposure, FS was significantly (P < 0.01) diminished in young 129, which was attributable to significant increases in end-systolic left ventricular diameter. With O₃ and CB combined, notable (P < 0.01) declines in heart rate and end-systolic posterior wall thickness occurred in young 129 mice. The IVH measurements showed striking (P < 0.05) compromises in cardiac function after CB and O₃ exposure; however, strain differences were undetectable. These results suggest that PM and O₃ exposures, alone and combined, lead to different cardiac functional changes, and these unique changes are age-specific and dependent on Nppa and Npr1 genes.

Keywords::

• Air pollution
• atrial natriuretic peptide
• cardiac structure and function
• cardiopulmonary regulation
• myocardial contractility

Acknowledgements

The authors would like to acknowledge the technical support of Vikas Misra and Nicole Sborz.

Declaration of interest

This study was supported in part by National Institute of Health Grants (NIA AG-21057) and the NIEHS center grant (P30 ES003819) at Johns Hopkins University Bloomberg School of Public Health.