Science Inventory

Ventricular transcriptional data provide mechanistic insights into diesel exhaust induced attenuation of cardiac contractile response and blood pressure

Citation:

Kodavanti, U., V. Bass, J. Crooks, B. Vallanat, H. Ren, M. Schladweiler, R. Thomas, Todd Krantz, C. King, C. Gordon, AND A. Ledbetter. Ventricular transcriptional data provide mechanistic insights into diesel exhaust induced attenuation of cardiac contractile response and blood pressure. Presented at SOT, March 10 - 14, 2013.

Impact/Purpose:

This abstract on the diesel exhaust effect on the heart will be presented at the National Society of Toxicology meeting in March 10-14, 2013.

Description:

Human exposures to near road ambient particulate matter and its major component, diesel exhaust (DE), have been associated with cardiovascular impairments however the mechanisms and the role of hypertension are not well understood. We have shown that DE exposure reduces blood pressure (BP) and cardiac contractility in healthy normotensive Wistar Kyoto (WKY) rats. We hypothesized that DE would induce differential myocardial gene expression changes that modulate myocardial contractility in WKY and spontaneously hypertensive (SH) rats, and that lowering BP in WKY and SH with hydralazine (HYD) would increase this effect of DE. Male WKY and SH rats were treated with HYD (150 mg/L) in drinking water for 10 days prior to exposure and until necropsy. All rats were exposed to clean air or freshly-generated whole DE (1500 g/m3), 5-hours/day for 2-days. Systolic BP was monitored using the tail-cuff method on days -10, 0, and 2. Left ventricular genome-wide expression was analyzed one day after final exposure using Illumina RatRef-12 BeadChips. As expected, WKY and SH rat’s ventricular gene expression patterns differed markedly. Surprisingly, DE exposure resulted in differential expression of 256 genes in WKY but none in SH rats. In WKY rats, the effect of HYD on expression patterns were nearly identical to changes induced by DE (same genes with same directional change); while HYD was without effect on expression changes in SH rats despite lowering BP. Genes inhibited by DE or HYD in WKY were induced at baseline in SH and vice versa. Genes downregulated by DE and HYD were related to sequestration of oxidants, inhibition of proteases, and membrane stability. The genes upregulated by DE and HYD in WKY included those involved in decreasing BP and muscle contraction as well as calcium homeostasis and apoptosis. In conclusion, acute DE exposure caused gene expression changes only in normotensive WKY rats; these changes mimicked those induced by HYD and are associa

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Product Published Date: 03/14/2013
Record Last Revised: 01/10/2017
OMB Category: Other
Record ID: 252067