Staudacher Torsten, Pech Bärbel, Tappe Michael, Gross Gerhard, Mühlbauer Bernd, Luippold Gerd
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Tübingen, Germany.
Hypertens Res. 2007 Jan;30(1):93-101. doi: 10.1291/hypres.30.93.
Alterations in the dopaminergic system may contribute to the development of hypertension. Recently, it has been reported that pentobarbital-anesthetized mice with deficient dopamine D(3) receptors showed renin-dependent elevation in blood pressure. In a series of experiments, we evaluated the contribution of the dopamine D(3) receptor to the renal sodium excretion and arterial blood pressure behavior in conscious as well as anesthetized dopamine D(3) receptor knockout (-/-) mice. The blood pressure measuring study was designed as a cross-over trial to investigate the influence of different sodium loads. The animals were fed a normal salt diet (0.6% NaCl, NS) for 1 week and afterwards a low (0.2% NaCl, LS) or a high salt diet (4.6% NaCl, HS) for 2 weeks. After the third week, the animals were switched to the corresponding protocol. Systolic blood pressure in conscious (-/-) mice measured by tail-cuff plethysmography was not different from that of wild-type (+/+) animals, irrespective of the time course or the salt diet. In another experiment, challenge of an acute sodium loading per gavage in conscious D(3) receptor (-/-) and (+/+) animals on HS or NS diet did not show significant differences in renal sodium excretion between the two genotypes. Additionally, animals were fed an NS diet for 1 week and an HS diet for another week. As expected, sodium excretion significantly increased after the change from the NS to the HS diet. A slightly lower urinary sodium excretion was observed when comparing D(3) receptor (-/-) mice to their corresponding (+/+) mice, both on an HS diet. Clearance experiments with anesthetized D(3) receptor (-/-) and (+/+) mice were performed to investigate the renal sodium excretion capacity, when exposed to a moderate volume expansion (VE). Urinary sodium excretion increased in response to the VE; however, no difference were observed between the two genotypes. Taking these results together, we conclude that in the present animal model renal dopamine D(3) receptors are not significantly involved in the regulation of blood pressure associated with a deficiency in renal sodium elimination.
多巴胺能系统的改变可能促成高血压的发展。最近，有报道称，多巴胺D(3)受体缺乏的戊巴比妥麻醉小鼠出现了肾素依赖性血压升高。在一系列实验中，我们评估了多巴胺D(3)受体对清醒及麻醉的多巴胺D(3)受体基因敲除(-/-)小鼠肾钠排泄和动脉血压行为的影响。血压测量研究设计为一项交叉试验，以研究不同钠负荷的影响。给动物喂食正常盐饮食（0.6% NaCl，NS）1周，之后喂食低（0.2% NaCl，LS）或高盐饮食（4.6% NaCl，HS）2周。第三周后，动物切换到相应方案。通过尾套体积描记法测量的清醒(-/-)小鼠的收缩压与野生型(+/+)动物的收缩压没有差异，无论时间进程或盐饮食如何。在另一项实验中，对清醒的D(3)受体(-/-)和(+/+)动物喂食HS或NS饮食，通过灌胃进行急性钠负荷挑战，两种基因型之间的肾钠排泄没有显著差异。此外，给动物喂食NS饮食1周，再喂食HS饮食1周。正如预期的那样，从NS饮食改为HS饮食后，钠排泄显著增加。在HS饮食中，将D(3)受体(-/-)小鼠与其相应的(+/+)小鼠进行比较时，观察到尿钠排泄略低。对麻醉的D(3)受体(-/-)和(+/+)小鼠进行清除实验，以研究在中等容量扩张（VE）时的肾钠排泄能力。尿钠排泄因VE而增加；然而，两种基因型之间没有观察到差异。综合这些结果，我们得出结论，在目前的动物模型中，肾多巴胺D(3)受体与肾钠排泄不足相关的血压调节没有显著关系。
