eNOS genotype-dependent correlation between whole blood lead and plasma nitric oxide products concentrations

Experimental data indicate that lead exposure decreases nitric oxide (NO) availability. However, no previous study has examined whether lead exposure affects plasma nitrite/nitrate (NOx) concentrations in humans. In addition, the T−786C polymorphism affects endothelial NO synthase (eNOS) expression and endogenous NO release. Here, we investigated whether there is an association between the circulating concentrations of NOx and the concentrations of lead in whole blood (B-Pb) and in plasma (P-Pb) from lead-exposed subjects. In addition, we also evaluated whether eNOS genotype for the T−786C polymorphism affects NOx concentrations in lead-exposed subjects. We studied 104 subjects exposed to lead who were non-smokers, 18–60 years of age, and not alcohol consumers. Genomic DNA was isolated from blood samples and genotypes for the T−786C polymorphism were determined by PCR and restriction fragment length digestion. Circulating NOx was determined by chemiluminescence. B-Pb and P-Pb were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. No significant correlations were found between NOx and B-Pb and P-Pb measured in the 104 subjects (all P > 0.05). However, while no significant correlation was found in subjects with TT genotype, a negative correlation was found between plasma NOx and B-Pb (r = 0.230, P = 0.048) and P-Pb (r = 0.194, P = 0.110) in subjects from TC+CC genotypes group. Our study shows a negative correlation between plasma NOx concentrations and B-Pb in carriers of the “C” allele, thus suggesting a possible mechanism possibly involved in lead exposure-induced increase in the susceptibility to cardiovascular diseases.