TY - JOUR
T1 - Air pollution alters brain and pituitary endothelin-1 and inducible nitric oxide synthase gene expression
AU - Thomson, Errol M.
AU - Kumarathasan, Prem
AU - Calderón-Garcidueñas, Lilian
AU - Vincent, Renaud
N1 - Funding Information:
Errol Thomson is the recipient of a doctoral scholarship from the Natural Sciences and Engineering Research Council of Canada. The authors are grateful to Josée Guénette, and DJ MacIntyre for conducting the inhalation exposures, and to Pat Goegan, Erica Blais, and Lorraine Casavant for the collection of biological samples. This work was supported by the Toxic Substances Research Initiative (TSRI-60) and Health Canada (SEP 4320010).
PY - 2007/10
Y1 - 2007/10
N2 - Recent work suggests that air pollution is a risk factor for cerebrovascular and neurodegenerative disease. Effects of inhaled pollutants on the production of vasoactive factors such as endothelin (ET) and nitric oxide (NO) in the brain may be relevant to disease pathogenesis. Inhaled pollutants increase circulating levels of ET-1 and ET-3, and the pituitary is a potential source of plasma ET, but the effects of pollutants on the expression of ET and NO synthase genes in the brain and pituitary are not known. In the present study, Fischer-344 rats were exposed by nose-only inhalation to particles (0, 5, 50 mg/m3 EHC-93), ozone (0, 0.4, 0.8 ppm), or combinations of particles and ozone for 4 h. Real-time reverse transcription polymerase chain reaction was used to measure mRNA levels in the cerebral hemisphere and pituitary 0 and 24 h post-exposure. Ozone inhalation significantly increased preproET-1 but decreased preproET-3 mRNAs in the cerebral hemisphere, while increasing mRNA levels of preproET-1, preproET-3, and the ET-converting enzyme (ECE)-1 in the pituitary. Inducible NO synthase (iNOS) was initially decreased in the cerebral hemisphere after ozone inhalation, but increased 24 h post-exposure. Particles decreased tumour necrosis factor (TNF)-α mRNA in the cerebral hemisphere, and both particles and ozone decreased TNF-α mRNA in the pituitary. Our results show that ozone and particulate matter rapidly modulate the expression of genes involved in key vasoregulatory pathways in the brain and pituitary, substantiating the notion that inhaled pollutants induce cerebrovascular effects. Crown
AB - Recent work suggests that air pollution is a risk factor for cerebrovascular and neurodegenerative disease. Effects of inhaled pollutants on the production of vasoactive factors such as endothelin (ET) and nitric oxide (NO) in the brain may be relevant to disease pathogenesis. Inhaled pollutants increase circulating levels of ET-1 and ET-3, and the pituitary is a potential source of plasma ET, but the effects of pollutants on the expression of ET and NO synthase genes in the brain and pituitary are not known. In the present study, Fischer-344 rats were exposed by nose-only inhalation to particles (0, 5, 50 mg/m3 EHC-93), ozone (0, 0.4, 0.8 ppm), or combinations of particles and ozone for 4 h. Real-time reverse transcription polymerase chain reaction was used to measure mRNA levels in the cerebral hemisphere and pituitary 0 and 24 h post-exposure. Ozone inhalation significantly increased preproET-1 but decreased preproET-3 mRNAs in the cerebral hemisphere, while increasing mRNA levels of preproET-1, preproET-3, and the ET-converting enzyme (ECE)-1 in the pituitary. Inducible NO synthase (iNOS) was initially decreased in the cerebral hemisphere after ozone inhalation, but increased 24 h post-exposure. Particles decreased tumour necrosis factor (TNF)-α mRNA in the cerebral hemisphere, and both particles and ozone decreased TNF-α mRNA in the pituitary. Our results show that ozone and particulate matter rapidly modulate the expression of genes involved in key vasoregulatory pathways in the brain and pituitary, substantiating the notion that inhaled pollutants induce cerebrovascular effects. Crown
KW - Air pollution
KW - Brain
KW - Endothelin
KW - Inducible nitric oxide synthase (iNOS)
KW - Ozone
KW - Particulate matter
KW - Pituitary
UR - http://www.scopus.com/inward/record.url?scp=34548414020&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2007.06.005
DO - 10.1016/j.envres.2007.06.005
M3 - Article
C2 - 17662977
AN - SCOPUS:34548414020
SN - 0013-9351
VL - 105
SP - 224
EP - 233
JO - Environmental Research
JF - Environmental Research
IS - 2
ER -