Skip to main content
SpringerLink
Log in

Lead-induced hypertension: Role of oxidative stress

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Chronic, low-level lead exposure causes hypertension in both animals and humans. The pathogenesis of leadinduced 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 β-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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Sharp DS, Osterloh J, Becker CE, et al.: Blood pressure and blood lead concentration in bus drivers. Environ Health Perspect 1988, 78:131–137.

    Article  PubMed  CAS  Google Scholar 

  2. Harlan WR: The relationship of blood lead levels to blood pressure in the U.S. population. Environ Health Perspect 1988, 78:9–13.

    Article  PubMed  CAS  Google Scholar 

  3. Khalil-Manesh F, Gonick HC, Weiler EW, et al.: Lead induced hypertension: possible role of endothelial factors. Am J Hypertens 1993, 6:723–729.

    PubMed  CAS  Google Scholar 

  4. Vaziri ND, Ding Y, Ni Z, Gonick HC: Altered nitric oxide metabolism and increased oxygen free radical activity in lead-induced hypertension: effect of lazaroid therapy. Kidney Int 1997, 52:1042–1046.

    Article  PubMed  CAS  Google Scholar 

  5. Gonick HC, Ding Y, Bondy SC, et al.: Lead-induced hypertension: interplay of nitric oxide and reactive oxygen species. Hypertension 1997, 30:1487–1492.

    PubMed  CAS  Google Scholar 

  6. Pirkle JL, Kaufmann RB, Brody DJ, et al.: Exposure of the U.S. population to lead, 1991–1994. Environ Health Perspect 1998, 106:745–750.

    Article  PubMed  CAS  Google Scholar 

  7. Lustberg M, Silbergold E: Blood lead levels and mortality. Arch Intern Med 2002, 162:2443–2449.

    Article  PubMed  CAS  Google Scholar 

  8. Vupputuri S, Muntner P, Bazzano LA, et al.: Blood lead level is associated with elevated blood pressure in blacks. Hypertension 2003, 41:463–468.

    Article  PubMed  CAS  Google Scholar 

  9. Hond DE, Nawrot T, Staessen JA: The relationship between blood pressure and blood lead in NHANES III. J Hum Hypertens 2002, 16:563–568. Relevant broad-based evaluation of the relationship between blood lead levels and blood pressure.

    Article  CAS  Google Scholar 

  10. Webb RC, Winquist RJ, Victery W, Vander AJ: In vivo and in vitro effects of lead on vascular reactivity in rats. Am J Physiol 1981, 241:H211-H216.

    PubMed  CAS  Google Scholar 

  11. Chang HR, Chen SS, Chen TJ, et al.: Lymphocyte beta-2 adrenergic receptors and plasma catecholamine levels in lead-exposed workers. Toxicol Appl Pharmacol 1996, 139:1–5.

    Article  PubMed  CAS  Google Scholar 

  12. Castellino N, Castellino P, Sannolo N: Inorganic Lead Exposure: Metabolism and Intoxication. Boca Raton: Lewis Publisher, 1995.

    Google Scholar 

  13. Sokas RK, Simmens S, Sophar K, et al.: Lead levels in Maryland construction workers. Am J Ind Med 1997, 31:188–194.

    Article  PubMed  CAS  Google Scholar 

  14. Menditto A, Morisi G, Spagnolo A, Mencotti A: Association of blood lead to blood pressure in men aged 55 to 75 years: effects of selected social and biochemical cofounders. Environ Health Perspect 1994, 102:107–111.

    PubMed  Google Scholar 

  15. Hu H, Aro A, Payton M, et al.: The relationship of bone and blood lead to hypertension: the normative aging study. JAMA 1996, 275:1171–1176.

    Article  PubMed  CAS  Google Scholar 

  16. Shen X, Rosen JF, Guo D, Wu S: Childhood lead poisoning in China. Sci Total Environ 1996, 181:101–109.

    Article  PubMed  CAS  Google Scholar 

  17. Postoli P, Maranelli G, Micciolo R: Is hypertension a confounding factor in the assessment of blood lead reference values? Sci Total Environ 1992, 120:127–134.

    Article  Google Scholar 

  18. Moller L, Kristensen TS: Blood lead as a cardiovascular risk factor. Am J Epidemiol 1992, 136:1091–1100.

    PubMed  CAS  Google Scholar 

  19. Pirkle JL, Schwartz J, Landis JR, Harlan WR: The relationship between blood lead levels and blood pressure and its cardiovascular risk implications. Am J Epidemiol 1985, 121:246–258.

    PubMed  CAS  Google Scholar 

  20. Rothenberg SJ, Kondrashov V, Manalo M, et al.: Increases in hypertension and blood pressure during pregnancy with increased bone lead levels. Am J Epidemiol 2002, 156:1079–1087.

    Article  PubMed  Google Scholar 

  21. Glenn BS, Stewart WF, Links JM, et al.: The longitudinal association of lead with blood pressure. Epidemiology 2003, 14:30–36.

    Article  PubMed  Google Scholar 

  22. Nash D, Magder L, Lustberg L, et al.: Blood lead, blood pressure, and hypertension in perimenopausal and postmenopausal women. J Am Med Assoc 2003, 289:1523–1532. Careful delineation of blood lead and blood pressure associations in relation to menopausal status.

    Article  CAS  Google Scholar 

  23. Staessen JA, Roels H, Lauwerys RR, Amery A: Low-level lead exposure and blood pressure. J Hum Hypertens 1995, 9:303–328.

    PubMed  CAS  Google Scholar 

  24. Hu H: Poorly controlled hypertension in a painter with chronic lead toxicity. Environ Health Perspect 2001, 109:95–99.

    Article  PubMed  CAS  Google Scholar 

  25. Nilsson U, Attewell R, Christoffersson JO, et al.: Kinetics of lead in the bone and blood after the end of occupational exposure. Pharmacol Toxicol 1991, 68:477–484.

    PubMed  CAS  Google Scholar 

  26. Rothenberg SJ, Kondrashov V, Manalo M, et al.: Increases in hypertension and blood pressure during pregnancy with increased bone lead levels. Am J Epidemiol 2002, 156:1079–1087.

    Article  PubMed  Google Scholar 

  27. Webber CE, Chettle DR, Bowins RJ, et al.: Hormone replacement therapy may reduce the return of endogenous lead from bone to the circulation. Environ Health Perspect 1995, 103:1150–1153.

    Article  PubMed  CAS  Google Scholar 

  28. Garrido Latorre F, Hernandez-Avila M, Tamayo Orozco J, et al.: Relationship of blood and bone lead to menopause and bone mineral density among middle-age women in Mexico City. Environ Health Perspect 2003, 111:631–636.

    Google Scholar 

  29. Fleet JC: Bone lead as a risk factor for hypertension in men. Nutr Rev 1996, 54:180–182.

    Article  PubMed  CAS  Google Scholar 

  30. Batuman V: Lead nephropathy, gout and hypertension. Am J Med Sci 1993, 305:241–247.

    Article  PubMed  CAS  Google Scholar 

  31. Houston DK, Johnson MA: Lead as a risk factor for hypertension in women. Nutr Rev 1999, 57:227–279.

    Google Scholar 

  32. Cheng Y, Schwartz J, Sparrow D, et al.: Bone lead and blood lead levels in relation to baseline blood pressure and the prospective development of hypertension: the normotensive aging study. Am J Epidemiol 2001, 153:164–171.

    Article  PubMed  CAS  Google Scholar 

  33. Muntner P, He J, Vupputuri S, et al.: Blood lead and chronic kidney disease in the general United States population: results from NHANES III. Kidney Int 2003, 63:1044–1050.

    Article  PubMed  Google Scholar 

  34. Vaziri ND, Ding Y, Ni Z: Nitric oxide synthase expression in the course of lead-induced hypertension. Hypertension 1999, 34:558–562.

    PubMed  CAS  Google Scholar 

  35. Vaziri ND, Liang K, Ding Y: Increased nitric oxide inactivation by reactive oxygen species in lead-induced hypertension. Kidney Int 1999, 56:1492–1498.

    Article  PubMed  CAS  Google Scholar 

  36. Dijkhorst-Oei LT, Koomans HA: Effects of a nitric oxide synthesis inhibitor on renal sodium handling and diluting capacity in humans. Nephrol Dial Transplant 1998, 13:587–593.

    Article  PubMed  CAS  Google Scholar 

  37. Harada S, Tokunaga S, Momohara M, et al.: Inhibition of nitric oxide formation in the nucleus tractus solitarius increases renal sympathetic nerve activity in rabbits. Circ Res 1993, 72:511–516.

    PubMed  CAS  Google Scholar 

  38. Qiu C, Muchant D, Beierwaltes WH, et al.: Evolution of chronic nitric oxide inhibition hypertension: relationship to renal function. Hypertension 1998, 31:21–26.

    PubMed  CAS  Google Scholar 

  39. Halliwell B: What nitrates tyrosine?: Is nitrotyrosine specific as a biomarker of peroxynitrite formation in vivo? FEBS Lett 1997, 411:157–160.

    Article  PubMed  CAS  Google Scholar 

  40. Ding Y, Gonick HC, Vaziri ND, et al.: Lead-induced hypertension: Increased hydroxyl radical production. Am J Hypertens 2001, 14:169–173.

    Article  PubMed  CAS  Google Scholar 

  41. Vaziri ND, Oveisi F, Ding Y: Role of increased oxygen free radical activity in the pathogenesis of uremic hypertension. Kidney Int 1998, 53:1748–1754.

    Article  PubMed  CAS  Google Scholar 

  42. Vaziri ND, Ni Z, Oveisi F, et al.: Enhanced nitric oxide inactivation and protein nitration by reactive oxygen species in renal insufficiency. Hypertension 2001, 39:135–141.

    Article  Google Scholar 

  43. Schnackenberg CG, Welch WJ, Wilcox CS: Normalization of blood pressure and renal vascular resistance in SHR with a membrane-permeable superoxide dismutase mimetic: role of nitric oxide. Hypertension 1998, 32:59–64.

    PubMed  CAS  Google Scholar 

  44. Schnackenberg CG, Wilcox CS: Two-week administration of tempol attenuates both hypertension and renal excretion of 8-Iso prostaglandin f2alpha. Hypertension 1999, 33:424–428.

    PubMed  CAS  Google Scholar 

  45. Vaziri ND, Ni Z, Oveisi F, Tarnavsky-Hobbs DL: Effect of antioxidant therapy on blood pressure and nitric oxide synthase expression in hypertensive rats. Hypertension 2000, 36:975–964.

    Google Scholar 

  46. Lopez-Ongil S, Hernandez-Perera O, Navarro-Antolin J, et al.: Role of reactive oxygen species in the signaling cascade of cyclosporine A-mediated up-regulation of eNOS in vascular endothelial cells. Br J Pharmacol 1998, 124:447–454.

    Article  PubMed  CAS  Google Scholar 

  47. Roberts CK, Vaziri ND, Wang XQ, Barnard RJ: Enhanced NO inactivation and hypertension induced by a high-fat, refined carbohydrate diet. Hypertension 2000, 36:423–429.

    PubMed  CAS  Google Scholar 

  48. Roberts CK, Vaziri ND, Liang K, Barnard RJ: Reversibility of chronic experimental syndrome X by diet modification. Hypertension 2000, 37:1323–1328.

    Google Scholar 

  49. Barton CH, Ni Z, Vaziri ND: Effect of server aortic banding above the renal arteries on nitric oxide synthase isotype expression. Kidney Int 2001, 59:654–661.

    Article  PubMed  CAS  Google Scholar 

  50. Barton CH, Ni Z, Vaziri ND: Enhanced nitric oxide inactivation in aortic coarctation-induced hypertension. Kidney Int 2001, 60:1083–1087.

    Article  PubMed  CAS  Google Scholar 

  51. Swei A, Lacy F, DeLano FA, Schmid-Schonbein GW: Oxidative stress in the Dahl hypertensive rat. Hypertension 1997, 30:1628–1633.

    PubMed  CAS  Google Scholar 

  52. Roggensack AM, Zhang Y, Davidge ST: Evidence for peroxynitrite formation in the vasculature of women with preeclampsia. Hypertension 1999, 33:83–89.

    PubMed  CAS  Google Scholar 

  53. Vaziri ND, Ding Y, Ni Z: Compensatory upregulation of NO synthase isoforms in lead-induced hypertension: reversal by an SOD-mimetic drug. J Pharmacol Exp Therap 2001, 298:679–685.

    CAS  Google Scholar 

  54. Vaziri ND, Wang XQ, Oveisi F, Rad B: Induction of oxidative stress by glutathione depletion causes hypertension in normal rats. Hypertension 2000, 36:142–146.

    PubMed  CAS  Google Scholar 

  55. Vaziri ND, Wang XQ: cGMP-mediated negative feedback regulation of endothelial nitric oxide synthase expression by nitric oxide. Hypertension 1999, 34:1237–1241.

    PubMed  CAS  Google Scholar 

  56. Ding Y, Gonick HC, Vaziri ND: Lead promotes hydroxyl radical generation and lipid peroxidation in cultured aortic endothelial cells. Am J Hypertens 2000, 13:552–555.

    Article  PubMed  CAS  Google Scholar 

  57. Ding Y, Vaziri ND, Gonick HC: Lead-induced hypertension. II. Response to sequential infusions of L-arginine, superoxide dismutase, and nitroprusside. Environ Res 1998, 76:107–113.

    Article  PubMed  CAS  Google Scholar 

  58. Vaziri ND, Ding Y: Effect of lead on NO synthase expression in coronary endothelial cells: Role of superoxide. Hypertension 2001, 37:223–226.

    PubMed  CAS  Google Scholar 

  59. Hsu PC, Guo YL: Antioxidant nutrients and lead toxicity. Toxicology 2002, 180:33–44. Comprehensive discussion of the role of antioxidants in modifying the effects of lead toxicity.

    Article  PubMed  CAS  Google Scholar 

  60. Vaziri ND, Lin CY, Farmand F, Sindhu R: Superoxide dismutase, catalase, glutathione peroxidase and NADPH oxidase in lead-induced hypertension. Kidney Int 2003, 63:186–194.

    Article  PubMed  CAS  Google Scholar 

  61. Marques M, Millas I, Jimenez A, et al.: Alteration of the soluble guanylate cyclase system in the vascular wall of lead-induced hypertension in rats. J Am Soc Nephrol 2001, 12:2594–2600.

    PubMed  CAS  Google Scholar 

  62. Courtois E, Marques M, Barrientos A, et al.: Lead-induced downregulation of soluble guanylate cyclase in isolated rat aortic segments mediated by reactive oxygen species and cycloxygenase-2. J Am Soc Nephrol 2003, 14:1464–1470. Description of the effect of lead-induced change in reactive oxygen species on soluble guanylate cyclase.

    Article  PubMed  CAS  Google Scholar 

  63. Chang HR, Chen SS, Tsao DA, et al.: Reduced vascular betaadrenergic receptors and catecholamine response in rats with lead-induced hypertension. Arch Toxicol 1977, 71:778–781.

    Article  Google Scholar 

  64. Carmignani M, Volpe AR, Boscolo P, et al.: Catecholamine and nitric oxide systems as targets of chronic lead exposure in inducing selective functional impairment. Life Sci 2000, 68:401–415.

    Article  PubMed  CAS  Google Scholar 

  65. Tsao DA, Yu HS, Cheng JT, et al.: The change of beta-adrenergic system in lead-induced hypertension. Toxicol Appl Pharmacol 2000, 164:124–133.

    Article  CAS  Google Scholar 

  66. Bertel O, Buhler FR, Ott J: Lead-induced hypertension: Blunted beta-adrenoceptor-mediated functions. Br Med J 1978, 1:551.

    PubMed  CAS  Google Scholar 

  67. Keeton TK, Campbell WB: The pharmacologic alteration of renin release. Pharmacol Rev 1980, 32:81–227.

    PubMed  CAS  Google Scholar 

  68. McAllister RG, Michelakis AM, Sandstead HH: Plasma renin activity in chronic plumbism. Arch Intern Med 1971, 127:919–923.

    Article  PubMed  Google Scholar 

  69. Boscolo P, Carmignani M: Neurohumoral blood pressure regulation in lead exposure. Environ Health Perspect 1988, 78:101–106.

    Article  PubMed  CAS  Google Scholar 

  70. Fleischer N, Mouw DR, Vander AJ: Chronic effects of lead on renin and renal sodium excretion. J Lab Clin Med 1980, 95:759–770.

    PubMed  CAS  Google Scholar 

  71. Wilke L: Early and Late Effects of Neonatal Lead Exposure or In Vitro Renin Release [bstract]. Thorofare, NJ: American Society of Nephrology; 1987.

    Google Scholar 

  72. Nowack R, Wiecek A, Ritz E: Lead and hypertension. Contrib Neprhol 1992, 100:25–34.

    CAS  Google Scholar 

  73. Carmignani M, Boscolo P, Brandi G: Plasma renin activity to occupational lead exposure. Acta Med Rom 1988, 26:277–289.

    CAS  Google Scholar 

  74. Camignani M, Boscolo P, Poma A, Volpe AR: Kininergic system and arterial hypertension following chronic exposure to inorganic lead. Immunopharmacol 1999, 44:105–110.

    Article  Google Scholar 

  75. Terada Y, Tomita K, Nonoguchi H, et al.: Expression of endothelin-3 RNA along rat nephron segments using polymerase chain reaction. Kidney Int 1993, 44:1273–1280.

    PubMed  CAS  Google Scholar 

  76. Cardenas A, Roels H, Bernard AM, et al.: Markers of early renal changes induced by industrial pollutants. II. Application to workers exposed to lead. Br J Ind Med 1993, 50:28–36.

    PubMed  CAS  Google Scholar 

  77. Hotter G, Fels LM, Closa D, et al.: Altered levels of urinary prostanoids in lead-exposed worker. Toxicol Lett 1995, 77:309–312.

    Article  PubMed  CAS  Google Scholar 

  78. Gonick HC, Ding Y, Vaziri ND: Effect of low lead exposure on eicosanoid excretion in rats. Prost Lipid Med 1998, 55:77–82.

    CAS  Google Scholar 

  79. Piccinini F, Favalli L, Chiari MC: Experimental investigations on the contraction induced by lead in arterial smooth muscle. Toxicology 1977, 8:43–51.

    Article  PubMed  CAS  Google Scholar 

  80. Kramer HJ, Gonick HC, Lu E: In vitro inhibition of Na-KATPase by trace metals: relation to renal and cardiovascular damage. Nephron 1986, 44:329–366.

    Article  PubMed  CAS  Google Scholar 

  81. Snowdon CT, Sanderson BA: Lead pica produced in rats. Science 1974, 193:92–94.

    Article  Google Scholar 

  82. Mahaffey KR, Goyer R: Dose-response to lead ingestion in rats fed low dietary calcium. J Lab Clin Med 1973, 82:92–100.

    PubMed  CAS  Google Scholar 

  83. Aungst BJ, Fung HL: The effects of dietary calcium on lead absorption, distribution and elimination kinetics in rats. J Toxicol Environ Health 1985, 16:147–159.

    Article  PubMed  CAS  Google Scholar 

  84. Hwang KY, Schwartz BS, Lee BK, et al.: Associations of lead exposure and dose measures with erythrocyte protein kinase C activity in 212 current Korean lead workers. Toxicol Sci 2001, 62:280–288.

    Article  PubMed  CAS  Google Scholar 

  85. Watts SW, Chai S, Webb RC: Lead acetate-induced contraction in rabbit mesenteric artery: interaction with calcium and protein kinase C. Toxicology 1995, 99:55–65.

    Article  PubMed  CAS  Google Scholar 

  86. Chai SS, Webb RC: Effects of lead on vascular reactivity. Environ Health Perspect 1988, 78:85–89.

    Article  PubMed  CAS  Google Scholar 

  87. Shelkovnikov SA, Gonick HC: Influence of lead on rat thoracic aorta contraction and relaxation. Am J Hypertension 2001, 14:873–878.

    Article  CAS  Google Scholar 

  88. Griffith LE, Guyatt GH, Cook RJ, et al.: The influence of dietary and non-dietary calcium supplementation on blood pressure: an updated meta-analysis of randomised controlled trials. Am J Hypertens 1999, 12:84–92.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology and Hypertension, University of California, Irvine, UCI Medical Center, 101 The City Drive, Building 53, Room 125, Route 81, 92868, Orange, CA, USA

    Nosratola D. Vaziri MD, MACP & Domenic A. Sica MD

Authors
  1. Nosratola D. Vaziri MD, MACP
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Domenic A. Sica MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vaziri, N.D., Sica, D.A. Lead-induced hypertension: Role of oxidative stress. Current Science Inc 6, 314–320 (2004). https://doi.org/10.1007/s11906-004-0027-3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-004-0027-3

Keywords

Search

Navigation