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Toxicology ; 243(3): 271-83, 2008 Jan 20.
Article in English | MEDLINE | ID: mdl-18077076

ABSTRACT

Epidemiological studies have suggested that fine particulate matter (f-PM) is associated with adverse effects on cardiovascular health. However, these effects on the cardiovascular system have not yet been fully elucidated. Using mRNA expression and correlation analyses, we designed the present study to elucidate (1) translocation of chemicals in inhaled f-PM to the heart, (2) induction of oxidative stress, one of the causes of cardiovascular diseases (CVDs), (3) mRNA expression related to CVDs, and (4) correlations among mRNA expression of various molecules and cardiovascular function. Wistar Kyoto male rats were exposed to concentrated ambient particles (CAPs, 0.6-1.5mg/m3) in Yokohama for 4 days (4.5h/day) or to filtered air for 3 days and CAPs for 1 day or to filtered air for 4 days. Messenger RNA expression and cardiovascular function were measured after the 4-day exposure. In samples of heart tissue, the mRNAs of cytochrome P450 (CYP) 1B1, a biomarker of exposure to chemicals; heme oxygenase-1 (HO-1), a marker of oxidative stress; and endothelin A (ET A) receptor, a receptor of vasoconstrictors, were up-regulated by CAPs; their levels were significantly correlated with the cumulative weight of CAPs in the exposure chamber. The up-regulation of ET A receptor mRNA was significantly correlated with the increase in HO-1 mRNA and weakly with the increase in mean blood pressure (Delta MBP). These results suggest the possibility that chemicals in CAPs might be translocated to the heart, where they induce oxidative stress and activate endothelin signaling, resulting in an increase in the blood pressure. The exposure to f-PM might thus affect cardiovascular function through activation of endothelin signaling.


Subject(s)
Heart/drug effects , Lung/drug effects , Myocardium/metabolism , Particulate Matter/toxicity , RNA, Messenger/metabolism , Animals , Aryl Hydrocarbon Hydroxylases/genetics , Blood Pressure/drug effects , Cytochrome P-450 CYP1B1 , Dose-Response Relationship, Drug , Heart/physiopathology , Heme Oxygenase-1/genetics , Interleukin-1beta/genetics , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Lung/metabolism , Lung/pathology , Male , Myocardium/pathology , Oxidative Stress/drug effects , Particle Size , Particulate Matter/administration & dosage , Particulate Matter/chemistry , RNA, Messenger/genetics , Rats , Rats, Inbred WKY , Receptor, Endothelin A/genetics , Receptor, Endothelin B/genetics , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Up-Regulation/drug effects , Up-Regulation/genetics
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