Skoczyńska Anna, Stojek Ewa, Górecka Helena, Wojakowska Anna
Department of Internal Medicine, Occupational Diseases and Hypertension, Wrocław Medical University, Poland.
Int J Occup Med Environ Health. 2003;16(2):169-77.
It is still unknown whether mechanisms of the hypertensinogenic effect of lead include changes in synthesis or release of vasoactive agents. This question is essential with regard to lead dissemination in the human environment as well as to frequent occurrence of arterial hypertension.
The aim of the study was to evaluate the effect of chronic exposure to lead on the vasoactive agents in blood in relation to redox system activity in vessel walls and to disturbances in homeostasis of essential metals. Using lead in double small, hypertensive doses we tried to estimate whether this effect dependents on the degree of lead exposure.
The study was performed on the male Buffalo rats which were given lead in drinking water, 50 or 100 ppm (lead acetate dissolved in distillate water) for 12 weeks. Control rats were given distillate water. Rats were fasted starting the night before the experiment, and the next day were anesthetized intramuscularly with ketaminum at a dose of 300 mg/kg body weight. The abdomen was opened and the aorta was isolated. Blood samples were drawn from heart, abdominal and thoracic aorta and then kidneys were excised. Serum nitric oxide and prostaglandin PGF(2alpha) concentrations were measured using R&D systems, and the plasma endothelin-1 level with enzymoimmunoassay; 5% homogenates of aorta were prepared from thoracic fragment in saccharose buffer. Lipid peroxides in homogenates were determined colorimetrically and glutathione was measured using colorimetric assay BIOXYTECH GSH-400. The concentration of metals (lead, copper and zinc) in blood and aorta were determined with a plasma spectrometer.
The study shows different changes in toxicological and biochemical status, depending on the dose of metal. Mean serum nitric oxide concentration was higher in rats treated with lead in a dose of 50 ppm (p < 0.01) or 100 ppm (p < 0.001) than in the control group. The plasma endothelin-1 level was lower in rats given lead in a dose of 50 ppm (p < 0.05) than in controls, whereas serum prostaglandin PGF(2alpha) concentration was similar in all animals. Glutathione concentration in aorta was higher in both groups of rats treated with lead (p < 0.001) in comparison to controls. There were positive linear dependencies between: (a) blood lead and serum nitric oxide; (b) aorta glutathione and serum nitric oxide; (c) copper in aorta and glutathione in aorta; (d) serum zinc and plasma endothelin-1 concentrations.
It was concluded, that lead in small doses increases synthesis and/or releases nitric oxide and its concentration in serum. This effect of lead is probably connected with the augmented production of glutathione in vessel walls. Additionally, lead in a dose of 50 ppm provokes the decrease in the level of plasma endothelin-1, probably through the decreased level of serum zinc. We suppose that the mechanisms responsible for the vascular effect of lead differ even within the range of hypertensive doses.
铅的致高血压作用机制是否包括血管活性物质合成或释放的变化尚不清楚。这个问题对于铅在人类环境中的传播以及动脉高血压的频繁发生至关重要。
本研究的目的是评估长期接触铅对血液中血管活性物质的影响，以及与血管壁氧化还原系统活性和必需金属稳态紊乱的关系。使用双倍小剂量的高血压剂量铅，我们试图估计这种影响是否取决于铅暴露程度。
本研究对雄性布法罗大鼠进行，给它们饮用含50或100 ppm（醋酸铅溶解于蒸馏水中）的水，持续12周。对照大鼠饮用蒸馏水。从实验前一天晚上开始大鼠禁食，第二天用剂量为300 mg/kg体重的氯胺酮进行肌肉麻醉。打开腹部，分离主动脉。从心脏、腹主动脉和胸主动脉采集血样，然后切除肾脏。使用R&D系统测量血清一氧化氮和前列腺素PGF(2α)浓度，用酶免疫测定法测量血浆内皮素-1水平；从胸段主动脉片段在蔗糖缓冲液中制备5%的匀浆。用比色法测定匀浆中的脂质过氧化物，用比色测定法BIOXYTECH GSH-400测量谷胱甘肽。用等离子光谱仪测定血液和主动脉中金属（铅、铜和锌）的浓度。
研究表明，根据金属剂量不同，毒理学和生化状态会有不同变化。用50 ppm（p < 0.01）或100 ppm（p < 0.001）剂量铅处理的大鼠，其平均血清一氧化氮浓度高于对照组。用50 ppm剂量铅处理的大鼠血浆内皮素-1水平低于对照组（p < 0.05），而所有动物的血清前列腺素PGF(2α)浓度相似。与对照组相比，两组用铅处理的大鼠主动脉中的谷胱甘肽浓度更高（p < 0.001）。以下之间存在正线性相关性：（a）血铅与血清一氧化氮；（b）主动脉谷胱甘肽与血清一氧化氮；（c）主动脉中的铜与主动脉中的谷胱甘肽；（d）血清锌与血浆内皮素-1浓度。
得出的结论是，小剂量铅会增加一氧化氮的合成和/或释放及其在血清中的浓度。铅的这种作用可能与血管壁中谷胱甘肽产量增加有关。此外，50 ppm剂量的铅可能通过降低血清锌水平导致血浆内皮素-1水平下降。我们推测，即使在高血压剂量范围内，铅对血管作用的机制也有所不同。
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