Air pollutants increase gene expression of the vasoconstrictor endothelin-1 in the lungs.
Inhalation of urban pollutants elevates the circulating levels of the vasoactive peptides endothelin (ET)-1 and ET-3 in rats. This effect could explain the association between episodic variations of urban pollutants and acute cardiopulmonary morbidity and mortality documented in epidemiological studies. Because the lungs are the primary source of circulating ET-1 and the main site of clearance from circulation, we investigated the response of endothelin system genes in the lungs of Fischer-344 rats after 4-h nose-only inhalation of 0.8 ppm ozone plus 49 mg/m(3) EHC-93 (Ottawa particles). The mRNA levels for preproET-1, preproET-3, endothelin-converting enzyme (ECE)-1, and ET receptor subtypes A and B were determined at 2 h, and 1, 2, 3, 7, and 14 days after exposure. The pollutants induced preproET-1 and ECE-1 (P<0.05) after 2 h, consistent with the notion of increased synthesis and conversion of the peptide ET-1 in lung endothelial cells. PreproET-3 mRNA was down-regulated at 2 h post-exposure (P<0.05), and returned to control levels by 24 h, indicating that induction of ET-3 in the lungs is not responsible for the sustained elevation of ET-3 in plasma reported after inhalation of pollutants. Our results indicate that lung endothelin system genes respond rapidly and transiently to inhalation of urban pollutants, consistent with the dynamics of urban pollutant health effects in the human population.
Thomson
Errol
E
Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Goegan
Patrick
P
Kumarathasan
Prem
P
Vincent
Renaud
R
D000280:Administration, Inhalation; D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D019332:Endothelin-1 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010126:Ozone / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction
D000393:Air Pollutants; D019332:Endothelin-1; D012333:RNA, Messenger; D010126:Ozone