Keiser J A, Vander A J, Germain C L
Toxicol Appl Pharmacol. 1983 Jun 15;69(1):127-37. doi: 10.1016/0041-008x(83)90128-x.
These experiments studied the influence of chronic lead exposure on the steady-state clearance of exogenous homologous renin in unanesthetized, unrestrained rats. Relative to time controls (TC), rats chronically exposed to 500 ppm lead in drinking water had significantly elevated basal plasma renin concentrations (PRC) (Pb = 12.0 +/- 1.6 ng/ml/hr, TC = 7.6 +/- 0.8). During the infusion of homologous renin sufficient to increase plasma renin approximately 10-fold, the clearance of renin was not different between the two groups (after 60-min infusion, Pb = 16.1 +/- 1.8 ml/kg/min, TC = 15.9 +/- 1.5). Rats exposed to 1000 ppm lead did not have higher PRCs than time controls (Pb = 10.9 +/- 2.2 TC = 9.2 +/- 1.8). The clearances of renin in these two groups were also not significantly different (Pb = 15.3 +/- 2.8 TC = 18.3 +/- 2.5). Renal renin concentrations were significantly elevated in the 500 ppm rats (Pb = 1426 +/- 110 micrograms/kidney, TC = 1065 +/- 118) consistent with an increased basal renin secretion, but were not elevated in the 1000-ppm rats. There were no significant differences in the clearances of sulfobromophthalein (BSP) between any of the groups. The renin infusion significantly reduced BSP clearance, but did not so equally in all groups. It is concluded that in unanesthetized, unrestrained rats the clearance of renin is not altered by chronic lead exposure of either 500 or 1000 ppm and that increased secretion of renin accounts for the elevated basal PRC observed in rats exposed to the lower dose of lead.
这些实验研究了慢性铅暴露对未麻醉、未束缚大鼠中外源性同源肾素稳态清除率的影响。相对于时间对照组(TC),长期饮用含500 ppm铅的水的大鼠基础血浆肾素浓度(PRC)显著升高(铅组 = 12.0±1.6 ng/ml/小时,TC组 = 7.6±0.8)。在输注同源肾素足以使血浆肾素增加约10倍的过程中,两组肾素的清除率没有差异(输注60分钟后,铅组 = 16.1±1.8 ml/kg/分钟,TC组 = 15.9±1.5)。暴露于1000 ppm铅的大鼠PRC并不高于时间对照组(铅组 = 10.9±2.2,TC组 = 9.2±1.8)。这两组肾素的清除率也没有显著差异(铅组 = 15.3±2.8,TC组 = 18.3±2.5)。500 ppm组大鼠的肾脏肾素浓度显著升高(铅组 = 1426±110微克/肾脏,TC组 = 1065±118),这与基础肾素分泌增加一致,但1000 ppm组大鼠的肾脏肾素浓度没有升高。各组间磺溴酞钠(BSP)的清除率没有显著差异。肾素输注显著降低了BSP清除率,但并非在所有组中都同等程度降低。结论是,在未麻醉、未束缚的大鼠中,500或1000 ppm的慢性铅暴露不会改变肾素的清除率,并且肾素分泌增加是低剂量铅暴露大鼠中观察到的基础PRC升高的原因。