Review Mechanisms of lead-induced hypertension and cardiovascular disease

2008; doi:10.1152/ajpheart.00158.2008.—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, alter-ing 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 vas-cular smooth muscle cell proliferation and phenotypic transformation, reduce tissue plasminogen activator, and raise plasminogen activator inhibitor-1 production. Vi