Lead promotes hydroxyl radical generation and lipid peroxidation in cultured aortic endothelial cells

Early studies by our group have shown that lead-induced hypertension (HTN) is closely related to enhanced activity of reactive oxygen species (ROS). I n addition, we have found indirect evidence that hydroxyl radical may be th e most likely culprit in lead-exposed animals. In the present study, rat ao rtic endothelial cells were incubated in the presence of 0, 0.01, 0.1, 0.5, and 1.0 ppm lead acetate for 1, 24, and 48 h. At the conclusion of the inc ubation period cells were harvested and the media were collected. Lipid per oxidation products were measured as malondialdehyde-thiobarbituric acid (MD A-TBA) in the medium and hydroxyl radical was measured as 2,3-dihydroxybenz oic acid (2,3 DHBA) in the cells. After exposure to lead for 48 h, MDA-TBA generation and 2,3 DHBA formation were significantly increased. These data clearly demonstrate that lead exposure promotes hydroxyl radical generation and induces oxidative stress in isolated endothelial cells, mimicking the effects observed in lead-exposed animals. Enhanced inactivation of endothel ium-derived nitric oxide by locally produced oxygen free radicals could con tribute to endothelial dysfunction and HTN in lead-exposed animals. (C) 200 0 American Journal of Hypertension, Ltd.