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Inhalation of Whole Diesel Exhaust but not Gas-Phase Components Affects In Vitro Platelet Aggregation in Hypertensive Rats
Citation:
THOMAS, R., M. SCHLADWEILER, A. D. Ledbetter, T. Krantz, D. W. DAVIES, J. H. Shannahan, AND U. P. KODAVANTI. Inhalation of Whole Diesel Exhaust but not Gas-Phase Components Affects In Vitro Platelet Aggregation in Hypertensive Rats. Presented at American Thoracic Society Conference, New Orleans, LA, May 09 - 14, 2010.
Impact/Purpose:
This Abstract examined the effect of exhaust and gas-phase components on platelet aggregation in healthy and hypertensive rats. Whole diesel exhaust caused increased aggregation only in hypertensive rats.
Description:
Rationale: Intravascular thrombosis and platelet aggregation are enhanced following exposure to diesel exhaust (DE) and other respirable particulate matter; however, the roles of endothelial and circulating mediators on platelet aggregation remain unclear. We hypothesized that adenosine diphosphate (ADP)-induced platelet aggregation will be enhanced in healthy and hypertensive rats following acute and 4 week inhalation of whole DE or gas-phase components. Methods: Male 1214 week old Wistar Kyoto (WKY) rats were treated with either hydralazine (to reduce blood pressure) or N-nitro-L-arginine methyl-ester hydrochloride (L-NAME) (to increase blood pressure), at 150 mg/L in drinking water, while spontaneously hypertensive (SH) rats were treated with hydralazine. Treatment began 10-days pre-exposure, and continued during exposure until necropsy. At exposure day-I, all rats were exposed to filtered air, DE gas-phase components or freshly-generated whole DE (1820 ug/rrr'), for 5 hours/day x 5 days/week x 4 weeks or for two days only. Hematological parameters were assessed in blood and adenosine-5'-diphosphate (ADP)-induced platelet aggregation was determined in vitro with a Platelet Aggregation Profiler (PAP-8E). Results: Although increased baseline levels ofplatelets, red blood cells, and hemoglobin were observed in SH relative to WKY, no major drug effects were noted. There were rat strain-related differences in ADP-induced platelet aggregation such that primary aggregation (PA) was reduced while disaggregation was increased in control SH relative to control WKY. Treatment with hydralazine or L-NAME alone did not significantly affect the aggregation parameters in the either strain at any time. There were no effects of DE or gas-phase components on platelet aggregation in WKY at any time point; however, there were small effects in SH following 2-day exposure. Two-day exposure to DE but not gas-phase components caused a 14% increase in PA, associated with a 19% increase in the rate of aggregation, 25% increase in overall aggregation and a 30% increase in the final aggregation, while there was a 23% reduction in disaggregation. Hydralazine-treated SH did not present any platelet aggregation effects following DE exposure. This increase in DE-induced platelet aggregation following 2-day exposure in SH was not apparent following 4-week exposure. Rather there was a trend of a decrease in aggregation in SH exposed to DE for 4-weeks. Conclusion: DE but not gas-phase components increased platelet aggregation in only hypertensive rats. These small DE effects on platelets might be exacerbated in humans with underlying cardiovascular disease. (Abstract does not represent USEPA policy).