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Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H454-65. doi: 10.1152/ajpheart.00158.2008. Epub 2008 Jun 20.

Mechanisms of lead-induced hypertension and cardiovascular disease.

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Division of Nephrology and Hypertension, UCI Medical Center, 101 The City Dr., Bldg. 53, Rm. 125, Rt. 81, Orange, CA 92868, USA.


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 Ca(2+) 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.

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