Lead-induced hypertension: interplay of nitric oxide and reactive oxygen species.
An elevation of mean blood pressure was found in rats treated with low lead (0.01% lead acetate) for 3 months, as contrasted to paired Sprague-Dawley control rats. In these rats, measurement of plasma and urine endothelins-1 and -3 revealed that plasma concentration and urinary excretion of endothelin-3 increased significantly after 3 months (plasma: lead group, 31.8+/-2.2, versus controls, 23.0+1.7 pg/mL, P<.001; urinary excretion: lead group, 46.6+11.7, versus controls, 35.6+6.7 pg/24 h, P<.05), whereas endothelin-1 was unaffected. Plasma and urinary nitric oxide (NO) and cyclic GMP concentrations were not significantly changed. However, assay of plasma and kidney cortex malondialdehyde by high-pressure liquid chromatography, as a measure of reactive oxygen species, was elevated in lead-treated rats compared with that in control rats (plasma: lead group, 4.74+1.27, versus controls, 2.14+.49 micromol/L, P<.001; kidney cortex: lead group, 28.75+3.46, versus controls, 16.38+2.37 nmol/g wet weight, P<.001). There was increased NO synthase activity in lead-treated rat brain cortex and cerebellum. In lead-treated rat kidney cortex, the endothelial constitutive NO synthase protein mass was unaffected, whereas the inducible NO synthase protein mass was increased. These data suggest a balance between increased NO synthesis and degradation (by reactive oxygen species) in lead-treated rats, which results in normal levels of NO. Thus, the hypertension may be related to an increase in the pressure substances, endothelin-3 and reactive oxygen species, rather than to an absolute decrease in nitric NO.
Gonick
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HC
University of California at Los Angeles, Cedars-Sinai Medical Center, The Burns and Allen Research Institute, 90048, USA. hgonick@ucla.edu
Ding
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Bondy
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SC
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Vaziri
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002531:Cerebellum / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D019332:Endothelin-1 / Q000097:blood / Q000652:urine; D019334:Endothelin-3 / Q000097:blood / Q000652:urine; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007672:Kidney Cortex / Q000201:enzymology; D007854:Lead / Q000633:toxicity*; D008297:Male; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000097:blood / Q000652:urine; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000502:physiology*
D019332:Endothelin-1; D019334:Endothelin-3; D009566:Nitrates; D009573:Nitrites; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D007854:Lead; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; C008261:lead acetate