Numerous animal and epidemiological studies support a causal relationship between lead exposure and hypertension. Cardiovascular effects other than elevated blood pressure have been observed in individuals occupationally exposed to lead and in children with histories of pica. Mechanisms proposed for lead's effect on the cardiovascular system include alterations in adrenergic receptor density, membrane cation transport, calcium binding proteins, and enzymes ranging from phosphodiesterase to protein kinase C. Despite reported adverse effects, the cardiovascular toxicity of lead remains controversial due a significant number of negative studies. The purpose of the present study was to determine if low-level exposure of rabbits to lead would produce concentration-dependent changes in myocardial proteins. Male Dutch Belted rabbits (n = 60) were randomized into four dose groups. Lead was administered as a lead acetate solution in sterile 5% dextrose via subcutaneous injection 3 times per week for 20 weeks. Dosing was adjusted weekly to achieve and maintain the target blood lead levels of 0, 20, 40, and 80 ug/dl for 15 weeks. Rabbits were killed by lethal injection. Hearts were removed into iced Hanks' buffer without perfusion, blotted and weighed. Lead exposures did not affect heart or body weights. Left ventricals were dissected away, quartered and frozen in liquid nitrogen. Blood and myocardial lead analyses were by graphite furnace atomic absorption spectroscopy. Myocardial concentrations of lead at sacrifice were 58 +/- 25, 69 +/- 23, 102 +/- 62, and 105 +/- 37 ng/g. Ventricular homogenates were prepared for 2D electrophoresis, the resulting gel patterns stained, and image analyzed. 808 individual proteins were resolved, 162 of which had coefficients of variation <20%. A number of proteins were tentatively identified based on coordinate positions homologous to other established 2D patterns. Despite variable expression of some protein spots, none of the protein abundances analyzed were consistently altered (P< .00 1) by the lead exposures studied. Results support the conclusion that a low-body burden of lead does not affect the myocardium of the rabbit.
The Toxicologist. Society of Toxicology 36th Annual Meeting, March 9-13, 2006, Cincinnati, Ohio