Pathogenesis of lead-induced hypertension: role of oxidative stress.
Chronic exposure to low levels of lead causes hypertension in humans and experimental animals. Several mechanisms have been shown to contribute to the pathogenesis of lead-induced hypertension: (1) avid oxidation and inactivation of endogenous nitric oxide (NO) by reactive oxygen species leading to functional NO deficiency; (2) increased sympathetic activity and circulating noradrenaline coupled with decreased vascular and elevated renal beta-adrenergic receptor density; (3) increased angiotensin-converting enzyme (ACE) activity and elevated plasma renin, angiotensin II and aldosterone levels; (4) heightened kininase I and kininase II activities; (5) possible increase in endothelin and thromboxane production; and (6) lead-mediated inhibition of vascular smooth muscle Na(+)-K+ ATPase leading to a rise in cellular Na+ and hence Ca2+ stores. This paper provides an overview of the epidemiology of lead-induced hypertension followed by a review of the available data on the above-mentioned topics.
Vaziri
Nosratola D
ND
Division of Nephrology and Hypertension, Departments of Medicine, Physiology and Biophysics, University of California, Irvine, USA. ndvaziri@uci.edu
D000818:Animals; D016232:Endothelins / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D007705:Kinins / Q000502:physiology; D007854:Lead / Q000633:toxicity*; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology; D011941:Receptors, Adrenergic / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology
D016232:Endothelins; D007705:Kinins; D011453:Prostaglandins; D011941:Receptors, Adrenergic; D007854:Lead; D009569:Nitric Oxide