Lead-induced hypertension: role of oxidative stress.
Chronic, low-level lead exposure causes hypertension in both animals and humans. The pathogenesis of lead-induced hypertension is multifactorial, including such diverse mechanisms as: inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species (ROS), leading to a functional deficiency in nitric oxide; heightened sympathetic activity and plasma norepinephrine together with depressed vascular and elevated renal beta-adrenergic receptor density; elevated plasma angiotensin-converting enzyme (ACE) activity, plasma renin activity (PRA), angiotensin II (Ang-II), and aldosterone levels; increased kininase I and kininase II activities; lead-induced inhibition of vascular smooth muscle Na(+)-K+ ATPase, leading to a rise in cellular Na+ and, hence, Ca2+; and a possible rise in endothelin and thromboxane generation. In this article, we present an overview of the epidemiology and proposed underlying mechanisms of lead-induced hypertension.
Vaziri
Nosratola D
ND
Division of Nephrology and Hypertension, University of California, Irvine, UCI Medical Center, 101 The City Drive, Building 53, Room 125, Route 81, Orange, CA 92868, USA. ndvaziri@uci.edu
Sica
Domenic A
DA
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D015986:Confounding Factors, Epidemiologic; D004781:Environmental Exposure; D006162:Guanylate Cyclase / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D007854:Lead / Q000009:adverse effects* / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D017382:Reactive Oxygen Species; D000804:Angiotensin II; D007854:Lead; D009569:Nitric Oxide; D006162:Guanylate Cyclase