Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic illnesses.

Population studies have demonstrated a link between lead exposure and subsequent development of hypertension (HTN) and cardiovascular disease.

In vivo and in vitro studies have shown that chronic lead exposure causes HTN and cardiovascular disease by promoting oxidative stress, limiting nitric oxide availability, impairing nitric oxide signaling, augmenting adrenergic activity, increasing endothelin production, altering the renin-angiotensin system, raising vasoconstrictor prostaglandins, lowering vasodilator prostaglandins, promoting inflammation, disturbing vascular smooth muscle Ca²⁺ signaling, diminishing endothelium-dependent vasorelaxation, and modifying the vascular response to vasoactive agonists.

Moreover, lead has been shown to cause endothelial injury, impede endothelial repair, inhibit angiogenesis, reduce endothelial cell growth, suppress proteoglycan production, stimulate vascular smooth muscle cell proliferation and phenotypic transformation, reduce tissue plasminogen activator, and raise plasminogen activator inhibitor-1 production.

Via these and other actions, lead exposure causes HTN and promotes arteriosclerosis, atherosclerosis, thrombosis, and cardiovascular disease.

In conclusion, studies performed in experimental animals, isolated tissues, and cultured cells have provided compelling evidence that chronic exposure to low levels of lead can cause HTN, endothelial injury/dysfunction, arteriosclerosis, and cardiovascular disease.

More importantly, these studies have elucidated the cellular and molecular mechanisms of lead's action on cardiovascular/renal systems, a task that is impossible to accomplish using clinical and epidemiological investigations alone.

^{oxidative stress; renin-angiotensin-aldosterone system; endothelin; catecholamines; adrenergic system; nitric oxide; endothelial dysfunction; endothelial cell; vascular smooth muscle; heart; atherosclerosis; heparan sulfate proteoglycans; thrombosis; angiogenesis; calcium signaling; antioxidant system; cGMP}

Historically, the main sources of lead exposure in the United States and many other countries were lead-based paint, leaded gasoline, lead-soldered plumbing fixtures, pipes, and canned foods, contaminated alcoholic beverages, lead-glazed kitchen/dining utensils, and mining and industrial contaminations, as well as occupational exposure.

 Since the banning of lead-based gasoline, paint, and solder, as well as passage and enforcement of industrial and environmental regulations, exposure to lead has declined significantly in the United States (53).

However, heavy ground contamination is a persistent source of lead exposure in the industrial societies. In addition, heavy exposure continues in countries where effective environmental and industrial regulations are nonexistent or not strictly enforced.

Recently, reclamation-recycling of discarded computers has emerged as a source of heavy lead exposure among workers involved in this process.

Lead is absorbed via the respiratory and gastrointestinal tracts and, occasionally, through the skin. Lead absorption via the respiratory tract is highly efficient, resulting in an average uptake of 40% of the inhaled lead (22).

The dominant route of exposure through the lung in adults is associated with smelting and burning processes, as well as inhalation of lead-containing dust from scraping, burning, or sanding lead paint from surfaces, a well as exhaust from vehicles and planes powered by lead-containing gasoline.

The gastrointestinal tract is less efficient, with 10–15% of the ingested lead being absorbed. In addition, tetraethyl lead, a previously common gasoline additive, is absorbed via the cutaneous route.

After absorption, lead is distributed in the blood, bone, and soft tissues. Approximately 99% of blood lead content is bound to red blood cells; only 1% is present in the plasma and is available for exchange with lead contained in the other tissues.

The half-life of lead in the blood is 30 days in individuals with normal renal function and longer in those with renal insufficiency (35, 62).

Am J Physiol Heart Circ Physiol 295: H454-H465

Nosratola D. Vaziri

Division of Nephrology and Hypertension, University of California, Irvine, Irvine, California

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