Lead acetate exposure inhibits nitric oxide synthase activity in capillaryand synaptosomal fractions of mouse brain

The toxicity of lead (Pb) is of concern to public health due to its persist ence in the environment. Brain is one of the major target organs where seve re neurologic alterations may be triggered after exposure. The primary effe cts of lead on brain functions are thought to be a damage to the nervous sy stem microvasculature. However, the mechanism of this toxicity is poorly un derstood. 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 determine d 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 syn aptosomes by following the conversion of H-3-L-arginine to H-3-L-citrulline . The results show that blood lead levels were dose-dependent. Brain capill aries showed a preferential accumulation of lead as compared to synaptosome s. With all Pb treatments, synaptosomal constitutive NOS was inhibited (abo ut 50% of control) while the inducible NOS activity in capillaries was enha nced. These data suggest that inhibition of cNOS activity and increase in i NOS may contribute to the Pb effects on the CNS.