Ultrafine particulate matter exposure impairs vasorelaxant response in superoxide dismutase 2-deficient murine aortic rings

ABSTRACT

Studies have linked exposure to ultrafine particulate matter (PM) and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism underlying observed adverse vascular effects. Advanced age is one factor known to decrease antioxidant defenses and confer susceptibility to the detrimental vascular effects seen following PM exposure. The present study was designed to investigate the vasomotor responses following ultrafine PM exposure in wild type (WT) and superoxide dismutase 2-deficient (SOD2^+/–) mice that possess decreased antioxidant defense. Thoracic aortic rings isolated from young and aged WT and SOD2^+/– mice were exposed to ultrafine PM in a tissue bath system. Aortic rings were then constricted with increasing concentrations of phenylephrine, followed by relaxation with rising amounts of nitroglycerin (NTG). Data demonstrated that ultrafine PM decreased the relaxation response in both young WT and young SOD2^+/– mouse aortas, and relaxation was significantly reduced in young SOD2^+/– compared to WT mice. Ultrafine PM significantly diminished the NTG-induced relaxation response in aged compared to young mouse aortas. After ultrafine PM exposure, the relaxation response did not differ markedly between aged WT and aged SOD2^+/– mice. Data demonstrated that the greater vascular effect in aortic rings in aged mice ex vivo after ultrafine PM exposure may be attributed to ultrafine PM-induced oxidative stress and loss of antioxidant defenses in aged vascular tissue. Consistent with this conclusion is the attenuation of NTG-induced relaxation response in young SOD2^+/– mice.

Abbreviations: H₂O₂: hydrogen peroxide; NTG: nitroglycerin; PAH: polycyclic aromatic hydrocarbons; PE: l-phenylephrine; PM: particulate matter; ROS: reactive oxygen species; SOD2: superoxide dismutase 2 deficient; WT: wild type

KEYWORDS:

• Aorta
• superoxide dismutase (SOD)
• ultrafine PM
• vasoreactivity

Acknowledgement

We kindly thank Dr. Aleksandr E. Vendrov for mouse aorta isolation.

Conflict of interest

The authors declare that they have no conflict of interest.

Disclaimer

The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. EPA, and approved for publication. The contents of this article should not be construed to represent agency policy nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

Additional information

Funding

This work was supported by the U.S. Environmental Protection Agency Intramural Research Program; the National Institutes of Health [Grant Numbers AG024282 and HL111664].