Health effects and time course of particulate matter on the cardiopulmonary system in rats with lung inflammation.
Recent epidemiological studies associate health effects and particulate matter in ambient air. Exacerbation of the particle-induced inflammation can be a mechanism responsible for increased hospitalization and death due to cardiopulmonary events in high-risk groups of the population. Systems regulating blood pressure that depend on lung integrity can be involved in progression of cardiovascular diseases. This study focused on the expression levels of various genes involved in cardiovascular and pulmonary diseases to assess their role in the onset of cardiovascular problems due to ambient particulate matter and compared these with the corresponding products. Rats with ozone-induced (1600 microg/m(3); 8 h) pulmonary inflammation were exposed to 0.5 mg, 1.5 mg, or 5 mg of particulate matter (PM) from Ottawa Canada (EHC-93) by intratracheal instillation. mRNA levels of various genes and their products were measured 2, 4, and 7 d after instillation. At 2 d after exposures to PM, tumor necrosis factor (TNF)-alpha levels in bronchoalveolar lavage fluid (BALF) were elevated approximately 4 times for the highest EHC-93 dose. MIP-2 protein levels in BALF were elevated approximately three times during the entire time period studied, whereas IL-6 levels were not affected compared to control groups. The MIP-2 mRNA levels revealed a similar pattern of induction. A twofold increase in endothelin (ET)-1 levels at d 2 and a 20% decrease in angiotensin-converting enzyme (ACE) activity at d 7 were measured in plasma. A 60% decrease of ACE and ET-1 mRNA levels suggested a possible endothelial damage in the lung blood vessels. Inducible nitric oxide synthase (iNOS) mRNA was found to be increased 3.5 times 2 d after instillation of the particles. Therefore, the endothelial damage could have been caused by large amounts of the free radical NO. Also, plasma levels of fibrinogen were elevated (20%), which could presumably increase blood viscosity, leading to decreased tissue blood flow. These changes in hematological and hemodynamic parameters observed in our study are in line with heart failure in high-risk groups of the population after high air pollution episodes.
Ulrich
Magda M W
MM
Division of Toxicology, Wageningen University, Wageningen, The Netherlands.
Alink
Gerrit M
GM
Kumarathasan
Premkumari
P
Vincent
Renaud
R
Boere
A John F
AJ
Cassee
Flemming R
FR
D000393:Air Pollutants / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002318:Cardiovascular Diseases / Q000235:genetics / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D016232:Endothelins / Q000097:blood; D007249:Inflammation; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000235:genetics / Q000473:pathology*; D008297:Male; D009573:Nitrites / Q000097:blood; D009929:Organ Size; D010126:Ozone / Q000633:toxicity; D010316:Particle Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000393:Air Pollutants; D016207:Cytokines; D016232:Endothelins; D009573:Nitrites; D012333:RNA, Messenger; D010126:Ozone