Gonick H C, Ding Y, Bondy S C, Ni Z, Vaziri N D
University of California at Los Angeles, Cedars-Sinai Medical Center, The Burns and Allen Research Institute, 90048, USA.
Hypertension. 1997 Dec;30(6):1487-92. doi: 10.1161/01.hyp.30.6.1487.
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.
与配对的斯普拉格-道利对照大鼠相比，用低剂量铅（0.01%醋酸铅）处理3个月的大鼠出现平均血压升高。在这些大鼠中，血浆和尿液中内皮素-1和-3的测量显示，3个月后内皮素-3的血浆浓度和尿排泄量显著增加（血浆：铅处理组，31.8±2.2，对照组为23.0+1.7 pg/mL，P<0.001；尿排泄量：铅处理组，46.6+11.7，对照组为35.6+6.7 pg/24 h，P<0.05），而内皮素-1未受影响。血浆和尿液中的一氧化氮（NO）以及环磷酸鸟苷浓度没有显著变化。然而，通过高压液相色谱法测定血浆和肾皮质丙二醛作为活性氧的指标，与对照大鼠相比，铅处理大鼠的该指标升高（血浆：铅处理组，4.74+1.27，对照组为2.14+.49 μmol/L，P<0.001；肾皮质：铅处理组，28.75+3.46，对照组为16.38+2.37 nmol/g湿重，P<0.001）。铅处理大鼠的脑皮质和小脑中一氧化氮合酶活性增加。在铅处理大鼠的肾皮质中，内皮型组成型一氧化氮合酶蛋白量未受影响，而诱导型一氧化氮合酶蛋白量增加。这些数据表明，铅处理大鼠中一氧化氮合成增加与（由活性氧）降解之间存在平衡，这导致一氧化氮水平正常。因此，高血压可能与升压物质内皮素-3和活性氧的增加有关，而不是与一氧化氮的绝对减少有关。
