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Ultrafine particulate matter exposure in vitro impairs vasorelaxant response in superoxide dismutase 2 deficient and aged murine aortic rings
Citation:
CARTER, J. D., H. TONG, A. E. Vendrov, K. C. Moinar, N. R. Madamanchi, D. DIAZ SANCHEZ, W. CASCIO, AND M. S. Runge. Ultrafine particulate matter exposure in vitro impairs vasorelaxant response in superoxide dismutase 2 deficient and aged murine aortic rings. Presented at American Thoracic Society Conference, San Francisco, CA, May 18 - 23, 2012.
Impact/Purpose:
This study indicates that the greater vascular effect , in aortic rings in aged mice in vitro after UFPM exposure is likely due to UFPM induced oxidative stress and loss ofanti-oxidant defense in aged vascular tissue.
Description:
Epidemiological studies positively associate exposure to inhaled ultrafine particulate matter (UFPM) and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism contributing to the adverse short-term vascular effects of air pollution exposure. Advanced age is one factor known to decrease anti-oxidant defense and confer susceptibility to the detrimental vascular health effects of PM exposure. The present study was designed to test the hypothesis that vasomotor effects induced by UFPM exposure are increased in aged mice and enhanced in superoxide dismutase 2 deficient (SOD2+/-) mice having decreased anti-oxidant defense. Thoracic aorta rings isolated from young (4 m old, n=13) and aged (16 m old, n=12) wild type (WT) (n=14) and SOD2+/- mice (n=ll) were exposed to 50 ug/ml Chapel Hill UFPM for 15 min in a tissue bath system. All aortic rings were then constricted with 1 uM phenylephrine, followed by relaxation with increasing concentrations of nitroglycerin (NTG). The degree of relaxation was expressed as a percentage of the maximum constriction induced by phenylephrine. Three-way analysis of variance (ANOVA) was utilized for statistical analysis. We demonstrated that UFPM significantly reduced the NTG-induced relaxation response in aged compared to young mouse aortas (p=0.012). While UFPM decreased the relaxation response in both young WT (p<0.001) and young SOD2+/- (p<0.001) mouse aortas, the relaxation was significantly less in young SOD2+/- mice compared to WT mice (p<0.01). After UFPM treatment the relaxation response did not differ between aged WT and aged SOD2+/- mice. This study indicates that the greater vascular effect , in aortic rings in aged mice in vitro after UFPM exposure is likely due to UFPM induced oxidative stress and loss of anti-oxidant defense in aged vascular tissue. Consistent with this conclusion is the attenuation of the NTG-induced relaxation response in young SOD2+/- mice. This abstract of a proposed presentation does not necessarily reflect EPA policy