You are here:
PULMONARY AND CARDIAC GENE EXPRESSION FOLLOWING ACUTE ULTRAFINE CARBON PARTICLE INHALATION IN HYPERTENSIVE RATS
THOMAS, R., V. HARDER, M. SCHLADWEILER, H. SCHULZ, M. SEMMLER, E. KARG, T. STOGER, S. TAKENAKA, AND U. P. KODAVANTI. PULMONARY AND CARDIAC GENE EXPRESSION FOLLOWING ACUTE ULTRAFINE CARBON PARTICLE INHALATION IN HYPERTENSIVE RATS. Presented at American Thoracic Society Annual Meeting, San Francisco, CA, May 18 - 23, 2007.
Inhalation of ultrafine carbon particles (ufCP) causes cardiac physiological changes without marked pulmonary injury or inflammation. We hypothesized that acute ufCP exposure of 13 months old Spontaneously Hypertensive (SH) rats will cause differential effects on the lung and heart expression of genes involved in blood coagulation, oxidative stress, and vasoconstriction. Male SH rats were exposed to air or ufCP (23 nm; 5x106 /cm3) for 24 hrs. Gene expression changes were assessed in lung and heart using real-time PCR. Inflammation and injury markers were analyzed in BAL fluid. In PCR using co-amplification of HPRT-1 and target genes, inter-animal variation of the housekeeping gene was observed that appeared to be target sequence-specific. In such cases, we used parallel amplification of housekeeping and target genes to eliminate co amplification-related interference. No significant increases in BAL fluid neutrophils or protein and other markers occurred which reflected a lack of increase in MIP-2 mRNA following ufCP exposure. However, lung HO-1 expression increased 94% over control in ufCP-exposed rats. Marked increase in endothelin receptor A (160% over control) occurred but no increase in receptor B. This was associated with a small increase in endothelin-1 expression in the lung. ufCP exposure also caused lung tissue factor gene expression to increase 72% over control whereas no increase in PAI-1 was noted. Among all genes examined in the heart, endothelin-1 and PAI-1 expression appeared to be decreased by ufCP. These data demonstrate that ufCP exposure may cause local pulmonary oxidative stress and activation of endothelin system associated with induction of blood coagulation but without affecting fibrinolysis.
Funded By: This abstract does not reflect US EPA policy. Supported in part by a Cooperative Agreement between NCBA and US EPA.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
EXPERIMENTAL TOXICOLOGY DIVISION
PULMONARY TOXICOLOGY BRANCH