Handbook of Vitamin C Research

334Antonio J. López-Farré, José J. Zamorano-León, Daniel Sacristán, et al.In the general non-smoking and adult population the main way for lead exposurepathway is food and water contaminated with lead. Average daily lead intake for adults in theUK is estimated at 1.6 μg from air, 20 μg from drinking water and 28 μg from food. Drinkingwater seems to be responsible for approximately 20 percent of the total daily exposureexperienced by the majority of the U.S population. However, in the case of children, leadpaint is the major source of lead exposure. The U.S. department of Housing and Urbandevelopment estimated that 38 millions home in the United State contained lead paint. Ofthose, 24 millions contained significant lead-based paint hazards. In 1984, as many as 3 to 4million American children were estimated to have blood lead levels greater than healthylevels [35-37].2.1. Lead Exposure Hypertension and Oxidative StressThe severity of lead toxicity depends on the duration, frequency and amount of exposure.In this regard, multiples studies developed in animals and human population have supportedthe casual relationship between low-level lead exposure and hypertension [38]. Numerousresearching groups have tried to clarify the molecular mechanisms by which exposure to lowlevels of lead induces hypertension. The results of these studies have showed variousmolecular pathways involved to lead-induced hypertension. At present, there are three mainmechanisms by which lead seem to trigger hypertension:1. increase in oxidative stress2. inhibition of nitric oxide synthesis3. reduction of the smooth muscle cells of the cyclic-GMP generating systemE. D. Willis published the earliest paper regarding lead-induced oxidative stress in 1965.It is now well recognized the ability of lead to stimulate the oxidative state. Although themechanisms by which lead induces oxidative stress are not completely understood, evidenceindicates that multiple mechanisms may be involved.Lead exposure causes oxidative stress in the kidneys and in cardiovascular tissues in vivoand in endothelial cells and vascular smooth muscle cells in vitro. Moreover, animal studieshave shown that lead-induced oxidative stress is, at least in part, responsible for lead-inducedhypertension. In this regard, reactive oxygen species inactivate endothelial-dependentvasorelaxation. Ding et al. showed that L-arginine infusion lowers arterial pressure to a muchgreater extent in lead-exposed rats than in control animals [39]. It was also found reduction ofnitric oxide availability in lead-treated rats. In this work, it was further showed that the rise inarterial pressure was accompanied by reduction of renal blood flow, related to a rise in renalvascular resistance similar to that observed in rats treated with a nitric oxide generatinginhibitor [40].Lead may also favour the oxidative stress altering the antioxidant enzyme activities suchas superoxide dismutase, catalase and gluthatione peroxidase [41-43]. Because lead as otherheavy metals such as mercury, have a high affinity for sulfhydryl groups, lead is shown toinhibit overall enzymes having functional SH groups. This inhibitory effect of lead on