Effect of superoxide dismutase mimetic, AEOL 10150 on the regulation of the endothelinergic system in lungs and heart of rats exposed to air pollutants

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Title: Effect of superoxide dismutase mimetic, AEOL 10150 on the regulation of the endothelinergic system in lungs and heart of rats exposed to air pollutants
Authors: Ganesh, Devi
Date: 2006
Abstract: Epidemiological studies have associated cardiopulmonary morbidity and mortality with air pollution. Inhalation of pollutants increases plasma levels of the vasoconstrictor peptide endothelin (ET)-1 and its precursor bigET-1 in experimental animals and human subjects, and induces an oxidative stress in the lungs. Changes of circulating ET-1 is attributed to increased de novo synthesis in lung endothelial cells and spillover in the systemic circulation. Clinical studies indicate that excess ET-1 can be detrimental to individuals with cardiovascular and pulmonary diseases. My hypothesis is that oxidative stress pathways in the alveoli mediate the regulation of the endothelinergic system in response to inhalation of air pollutants. I have tested this hypothesis in male Fischer-344 rats by blocking a potential superoxide surge during or after inhalation of pollutants with a superoxide dismutase (SOD) mimetic drug, AEOL 10150. Rats were injected with 2mg/kg of AEOL 10150 two hours prior to inhalation exposure for four hours to pollutants, and sacrificed immediately or 24 hours post exposure. Treatment with the SOD mimetic abrogated the increase in expression of preproET-1 mRNA and ECE-1 mRNA and plasma ET-1 levels caused by the air pollutants. This suggests that oxidative stress pathways contribute to the regulation of endothelinergic system.
URL: http://hdl.handle.net/10393/27135
http://dx.doi.org/10.20381/ruor-11932
CollectionTh├Ęses, 1910 - 2010 // Theses, 1910 - 2010
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