Keiser J A, Vander A J, Germain C L
Toxicol Appl Pharmacol. 1983 Jun 15;69(1):117-26. doi: 10.1016/0041-008x(83)90127-8.
The disappearance rate of renin from plasma was evaluated in both acutely and chronically lead-exposed rabbits. In addition, the effects of lead (Pb) on in vitro renin secretion were determined with rabbit renal cortical slices. Rabbits acutely exposed to Pb (0.3 to 2.0 mg/kg, iv) demonstrated no increase in plasma renin activity (PRA), but a markedly prolonged disappearance of renin following nephrectomy. Together, these observations suggest that renin secretion must have been inhibited; consistent with this hypothesis was the finding that rabbit renal cortical slices exposed to Pb (10(-5) or 10(-6) M) in vitro secreted significantly less renin than did controls. Thus, the effects of large acute doses of Pb in the rabbit are simultaneous inhibition of both renin secretion and clearance. Chronically Pb-exposed rabbits (500 or 1000 ppm in drinking water) had renin half-lives that were not different from controls (6 to 8 min). PRA was also not significantly different in the three groups. Renal slices from both groups of Pb-exposed rabbits secreted significantly more renin in vitro compared to controls, despite the fact that renal renin concentrations were similar in the three groups. However, the responsiveness to a beta adrenergic stimulus was significantly lower in the slices from rabbits treated with 1000 ppm Pb. Taken together these data suggest that PRA in the chronically Pb-exposed rabbit reflects a tendency for increased basal renin secretion, but a counteracting suppression of renin release secondary to adrenergically mediated stimuli; thus, PRA might be reduced, unchanged, or elevated depending upon experimental conditions. Clearance of renin does not seem to be altered in the chronically Pb-exposed rabbit.
在急性和慢性铅暴露的家兔中评估了肾素从血浆中的消失率。此外,用家兔肾皮质切片测定了铅(Pb)对体外肾素分泌的影响。急性暴露于Pb(0.3至2.0mg/kg,静脉注射)的家兔血浆肾素活性(PRA)没有增加,但肾切除术后肾素的消失明显延长。这些观察结果共同表明肾素分泌一定受到了抑制;与此假设一致的是,体外暴露于Pb(10^(-5)或10^(-6)M)的家兔肾皮质切片分泌的肾素明显少于对照组。因此,家兔中大量急性剂量的Pb的作用是同时抑制肾素分泌和清除。慢性铅暴露的家兔(饮用水中含500或1000ppm)的肾素半衰期与对照组无差异(6至8分钟)。三组的PRA也无显著差异。尽管三组的肾肾素浓度相似,但两组铅暴露家兔的肾切片在体外分泌的肾素明显多于对照组。然而,用1000ppm Pb处理的家兔的切片对β肾上腺素能刺激的反应性明显较低。综合这些数据表明,慢性铅暴露家兔的PRA反映了基础肾素分泌增加的趋势,但继发于肾上腺素能介导的刺激的肾素释放有抵消性抑制;因此,根据实验条件,PRA可能降低、不变或升高。慢性铅暴露家兔中肾素的清除似乎没有改变。