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Hypertension. 1997;30:1487-1492

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(Hypertension. 1997;30:1487-1492.)
© 1997 American Heart Association, Inc.


Articles

Lead-Induced Hypertension

Interplay of Nitric Oxide and Reactive Oxygen Species

Harvey C. Gonick; Yaoxian Ding; Steven C. Bondy; Zhenmin Ni; ; Nosratola D. Vaziri

From the University of California, at Los Angeles and Irvine and Cedars-Sinai Medical Center, The Burns and Allen Research Institute, Los Angeles (H.C.G.) and the University of California, Irvine (Y.D., S.C.B., Z.N., N.D.V.).

Abstract 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 µmol/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.


Key Words: nitric oxide • endothelins • reactive oxygen species • lead




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