Air pollution alters brain and pituitary endothelin-1 and inducible nitric oxide synthase gene expression.
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, 50mg/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)-alpha mRNA in the cerebral hemisphere, and both particles and ozone decreased TNF-alpha 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.
Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ont., Canada K1A 0K9.
Errol M
EM
Thomson
Prem
P
Kumarathasan
Lilian
L
Calderón-Garcidueñas
Renaud
R
Vincent
D000280:Administration, Inhalation; D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D010126:Ozone / Q000633:toxicity*; D052638:Particulate Matter / Q000633:toxicity*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D019332:Endothelin-1; D052638:Particulate Matter; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat