Effect of lead acetate on nitrite production by murine brain endothelial cell cultures

• Published in: Toxicology and applied pharmacology Vol. 126; no. 1; p. 191
• Main Authors: Blazka, M E, Harry, G J, Luster, M I
• Format: Journal Article
• Language: English
• Published: United States 01-05-1994
• Subjects: Amino Acid Oxidoreductases - drug effects; Animals; Brain - blood supply; Calcium Chloride - metabolism; Cells, Cultured; Dose-Response Relationship, Drug; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Interferon-gamma - pharmacology; L-Lactate Dehydrogenase - drug effects; Lipopolysaccharides - pharmacology; Mice; Mice, Inbred BALB C; Nitric Oxide Synthase; Nitrites - metabolism; Organometallic Compounds - toxicity; Protein Biosynthesis; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0041-008X
• DOI: 10.1006/taap.1994.1107

One of the mechanisms by which lead may cause a perturbation in the nervous system is the alteration of endothelial cell function. This study investigated the effect of lead acetate on constitutive and cytokine-induced production of nitrite, a marker of nitric oxide, in brain microvascular endothelial cells. Nitric oxide synthase may be a target for lead and changes in its function can result in a cascade of physiological effects seen in vivo. Concentrations of 10, 100, and 1000 nM lead acetate, in the presence or absence of 100 ng lipopolysaccharide/ml, 400 U interferon-gamma/ml and 100 U tumor necrosis factor-alpha/ml, were added to confluent cultures of brain microvascular endothelial cells. Concentrations of lead acetate as low as 10 nM decreased constitutive levels of nitrite by 50% without inhibiting the inducible levels. Addition of 1 microM lead acetate had no effect on [3H]L-leucine incorporation, lactate dehydrogenase release, or cellular morphology, indicating that the effect was selective. Increasing the concentration of extracellular calcium to 2 mM abolished the inhibitory effect of lead acetate on the constitutive production of nitrite. These studies suggest that low concentrations of lead are capable of inhibiting nitrite produced by the calcium-dependent constitutive form of nitric oxide synthase while the calcium-independent, inducible form of nitric oxide synthase is not affected. These data provide another testable hypothesis for the as yet undetermined mechanisms of lead neurotoxicity.