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 VSports手机版. 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. .