One-month diesel exhaust inhalation produces hypertensive gene expression pattern in healthy rats.
BACKGROUND
Exposure to diesel exhaust (DE) is linked to vasoconstriction, endothelial dysfunction, and myocardial ischemia in compromised individuals.


OBJECTIVE
We hypothesized that DE inhalation would cause greater inflammation, hematologic alterations, and cardiac molecular impairment in spontaneously hypertensive (SH) rats than in healthy Wistar Kyoto (WKY) rats.


RESULTS
Male rats (12-14 weeks of age) were exposed to air or DE from a 30-kW Deutz engine at 500 or 2,000 microg/m3, 4 hr/day, 5 days/week for 4 weeks. Neutrophilic influx was noted in the lung lavage fluid of both strains, but injury markers were minimally changed. Particle-laden macrophages were apparent histologically in DE-exposed rats. Lower baseline cardiac anti-oxidant enzyme activities were present in SH than in WKY rats; however, no DE effects were noted. Cardiac mitochondrial aconitase activity decreased after DE exposure in both strains. Electron microscopy indicated abnormalities in cardiac mitochondria of control SH but no DE effects. Gene expression profiling demonstrated alterations in 377 genes by DE in WKY but none in SH rats. The direction of DE-induced changes in WKY mimicked expression pattern of control SH rats without DE. Most genes affected by DE were down-regulated in WKY. The same genes were down-regulated in SH without DE producing a hypertensive-like expression pattern. The down-regulated genes included those that regulate compensatory response, matrix metabolism, mitochondrial function, and oxidative stress response. No up-regulation of inflammatory genes was noted.


CONCLUSIONS
We provide the evidence that DE inhalation produces a hypertensive-like cardiac gene expression pattern associated with mitochondrial oxidative stress in healthy rats.
Gottipolu
Reddy R
RR
Experimental Toxicology Division, National Health & Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
Wallenborn
J Grace
JG
Karoly
Edward D
ED
Schladweiler
Mette C
MC
Ledbetter
Allen D
AD
Krantz
Todd
T
Linak
William P
WP
Nyska
Abraham
A
Johnson
Jo Anne
JA
Thomas
Ronald
R
Richards
Judy E
JE
Jaskot
Richard H
RH
Kodavanti
Urmila P
UP
D000818:Animals; D005786:Gene Expression Regulation; D006973:Hypertension / Q000235:genetics*; D008297:Male; D046529:Microscopy, Electron, Transmission; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D001335:Vehicle Emissions / Q000633:toxicity*
D001335:Vehicle Emissions