Lead acetate exposure inhibits nitric oxide synthase activity in capillary and synaptosomal fractions of mouse brain.
The toxicity of lead (Pb) is of concern to public health due to its persistence in the environment. Brain is one of the major target organs where severe neurologic alterations may be triggered after exposure. The primary effects of lead on brain functions are thought to be a damage to the nervous system microvasculature. However, the mechanism of this toxicity is poorly understood. Nitric oxide synthase (NOS) may be a target for lead and changes in its function can result in a cascade of pathophysiological effects that may be observed in isolated capillaries and synaptosomes. We have determined the concentration of lead in blood, capillaries and synaptosomes in brain from mice receiving 0, 250, 500, and 1000 ppm of lead for 14 days, through the drinking water. NOS activity was determined in the capillaries and synaptosomes by following the conversion of 3H-L-arginine to 3H-L-citrulline. The results show that blood lead levels were dose-dependent. Brain capillaries showed a preferential accumulation of lead as compared to synaptosomes. With all Pb treatments, synaptosomal constitutive NOS was inhibited (about 50% of control) while the inducible NOS activity in capillaries was enhanced. These data suggest that inhibition of cNOS activity and increase in iNOS may contribute to the Pb effects on the CNS.
Garcia-Arenas
G
G
Area de Toxicología, Centro Nacional de Salud Ambiental, SSA, Mexico.
Claudio
L
L
Perez-Severiano
F
F
Rios
C
C
D000818:Animals; D001120:Arginine / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002956:Citrulline / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007854:Lead / Q000032:analysis / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009942:Organometallic Compounds / Q000633:toxicity*; D011897:Random Allocation; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D009942:Organometallic Compounds; D002956:Citrulline; D007854:Lead; D001120:Arginine; D019001:Nitric Oxide Synthase; C008261:lead acetate