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DIFFERENCES IN CARDIOVASCULAR RESPONSE TO PM EXPOSURE BETWEEN SPONTANEOUSLY HYPERTENSIVE STROKE-PRONE (SHSP) AND WISTAR-KYOTO (WKY) RATS.
Citation:
CARLL, A. P., W. ROWAN, G. WALLENBORN, D. W. WINSETT, M. SCHLADWEILER, L. WICHERS, D. L. COSTA, U. P. KODAVANTI, AND W. P. WATKINSON. DIFFERENCES IN CARDIOVASCULAR RESPONSE TO PM EXPOSURE BETWEEN SPONTANEOUSLY HYPERTENSIVE STROKE-PRONE (SHSP) AND WISTAR-KYOTO (WKY) RATS. Presented at 45th Annual Society of Toxicology Meeting 2006, San Diego, CA, March 05 - 09, 2006.
Description:
ABSTRACT BODY: Epidemiological studies have shown that cardiovascular morbidity and mortality are associated with exposure to elevated levels of ambient particulate matter (PM), notably in people with pre-existing cardiopulmonary disease. To better understand the mechanisms of PM-induced cardiac toxicity, we used radiotelemetry methodology to compare the cardiac and thermoregulatory responses of SHSP to those of WKY rats following exposure to a model emission particle with a metal profile resembling ambient PM. Three groups (n=4/group; male; 110d) SHSP and WKY were exposed to saline, 3.33 mg/kg, or 8.33 mg/kg of an oil combustion-derived PM (HP12) via intratracheal instillation (IT). Heart rate (HR) and core temperature (Tco) data were acquired at 10-minute intervals over the course of the three-week study. Using a novel statistical approach (Fishing License Method; Nadziejko et al., 2004), we examined these time series data for the 120 hours following the challenge. Restricting our analysis to effects with a minimum duration of 3 hours, we found a significant decrease in HR for the high dose groups for both strains when compared to control, with a more robust response in the WKY strain (WKY:-60 bpm, SHSP:-35 bpm). There was no significant response in the low dose group for either strain. The effects for the SHSP appeared 30 minutes after IT, whereas the effects for the WKY appeared ~15 hours post-IT. Immediate drops in Tco were seen following challenge for both strains with the larger effect present in the WKY (WKY=1.65 C; SHSP=0.74 C). Assuming that the 'hypothermic response' (Watkinson et al., 1993) in rodents is protective, this finding suggests there may be a heightened vulnerability in the SHSP rat. (Abstract does not represent EPA policy. This research was supported by EPA CT829471 and EPO5D000528.)