Clinical evidence for lead-induced inhibition of nitric oxide formation
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Lead exposure has been associated with increased cardiovascular risk, which may result, at least in part, from lead-induced increases in oxidative stress and depressed nitric oxide (NO) availability. However, no previous clinical study has examined whether lead exposure is associated with significant effects on biomarkers of NO activity (plasma nitrites, nitrates, and cyclic guanosine 3′,5′-monophosphate; cGMP). We investigated whether there is an association between the circulating concentrations of nitrites, nitrates, and cGMP and the concentrations of lead in whole blood (B-Pb) or plasma (P-Pb) from 62 lead-exposed subjects (30 men and 32 women). P-Pb was determined by inductively coupled plasma mass spectrometry and B-Pb by graphite furnace atomic absorption spectrometry. Plasma nitrite and nitrate concentrations were measured using an ozone-based chemiluminescence assay. Plasma cGMP concentrations were measured using a commercial enzyme immunoassay. We found a negative correlation between plasma nitrite and B-Pb concentrations (r = −0.358; P = 0.004), and between plasma nitrite and P-Pb concentrations (r = −0.264; P = 0.038), thus suggesting increased inhibition of NO formation with increasing B-Pb or P-Pb concentrations. However, no significant correlations were found between plasma nitrate or cGMP and B-Pb or P-Pb concentrations (all P > 0.05). These findings suggest a significant inhibitory effect of lead exposure on NO formation and provide clinical evidence for a biological mechanism possibly involved the association between lead exposure and increased cardiovascular risk.
KeywordsCyclic GMP Lead toxicology Nitric oxide Nitrates Nitrites Plasma lead Whole blood lead
- ATSDR (1999) Toxicological Profile for Lead. US Department of Health and Human Services, Public Health Services, AtlantaGoogle Scholar
- Hibbs JB Jr, Westenfelder C, Taintor R, Vavrin Z, Kablitz C, Baranowski RL, Ward JH, Menlove RL, McMurry MP, Kushner JP et al (1992) Evidence for cytokine-inducible nitric oxide synthesis from l-arginine in patients receiving interleukin-2 therapy. J Clin Invest 89:867–877PubMedCrossRefGoogle Scholar
- Kleinbongard P, Dejam A, Lauer T, Rassaf T, Schindler A, Picker O, Scheeren T, Godecke A, Schrader J, Schulz R, Heusch G, Schaub GA, Bryan NS, Feelisch M, Kelm M (2003) Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals. Free Radic Biol Med 35:790–796PubMedCrossRefGoogle Scholar
- Montenegro MF, Barbosa F Jr, Sandrim VC, Gerlach RF, Tanus-Santos JE (2006) A polymorphism in the delta-aminolevulinic acid dehydratase gene modifies plasma/whole blood lead ratio. Arch Toxicol (in press). DOI 10.1007/s00204-005-0056-yGoogle Scholar