Ragsdale N V, Lynd M, Chevalier R L, Felder R A, Peach M J, Carey R M
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville.
Hypertension. 1990 Jun;15(6 Pt 2):914-21. doi: 10.1161/01.hyp.15.6.914.
Dopamine-1 (DA1) receptors in the renal tubules may be involved in the regulation of sodium homeostasis. To test this hypothesis, fenoldopam, a selective DA1 agonist, was infused at 0.05 microgram/kg/min i.v. in 16 normal male subjects in metabolic balance at 300 or 10 meq sodium. Renal function studies were performed by standard p-aminohippurate, inulin, and lithium clearances for three periods: 1) precontrol (2 hours), 2) experimental (3 hours), and 3) postcontrol (2 hours). DA1 receptor stimulation in sodium-loaded individuals increased the following parameters during the experimental period: urine flow rate, from 12.5 +/- 0.4 to 15.5 +/- 0.5 ml/min (p less than 0.05); urinary sodium excretion, from 309 +/- 12 to 489 +/- 18 mu eq/min (p less than 0.001); renal plasma flow, from 631 +/- 19 to 717 +/- 21 ml/min (p less than 0.005); fractional sodium excretion, from 2.2 +/- 0.1% to 3.4 +/- 0.1% (p less than 0.001); fractional lithium excretion, from 26.2 +/- 0.7% to 32.1 +/- 0.8% (p less than 0.005); and distal sodium load, from 10.7 +/- 0.4 to 13.8 +/- 0.5 ml/min (p less than 0.05). The increase in fractional sodium excretion was greater than that of fractional lithium excretion (p less than 0.0001). Distal sodium reabsorption decreased from 78.3 +/- 0.8% to 73.2 +/- 1.1% but the change was not statistically significant. In contrast, sodium-depleted subjects exhibited no significant changes except in renal plasma flow, which rose from 550 +/- 13 to 625 +/- 17 ml/min (p less than 0.0001). Glomerular filtration rate remained unchanged through the entire study. These results indicate that diuretic and natriuretic responses are mediated by DA1 receptors at both proximal and distal tubular sites. Attenuation of the DA1 natriuretic response during sodium depletion suggests a direct inhibition of cellular DA1 mechanisms in the renal tubule or recruitment of nondopaminergic compensatory homeostatic mechanisms within the kidney.
肾小管中的多巴胺 -1（DA1）受体可能参与钠稳态的调节。为验证这一假说，对16名处于300或10毫当量钠代谢平衡状态的正常男性受试者，以0.05微克/千克/分钟的速率静脉输注选择性DA1激动剂非诺多泮。通过标准对氨基马尿酸、菊粉和锂清除率进行三个阶段的肾功能研究：1）预对照期（2小时），2）实验期（3小时），3）后对照期（2小时）。在实验期，钠负荷个体的DA1受体刺激使以下参数增加：尿流率，从12.5±0.4增至15.5±0.5毫升/分钟（p＜0.05）；尿钠排泄，从309±12增至489±18微当量/分钟（p＜0.001）；肾血浆流量，从631±19增至717±21毫升/分钟（p＜0.005）；钠排泄分数，从2.2±0.1%增至3.4±0.1%（p＜0.001）；锂排泄分数，从26.2±0.7%增至32.1±0.8%（p＜0.005）；远端钠负荷，从10.7±0.4增至13.8±0.5毫升/分钟（p＜0.05）。钠排泄分数的增加大于锂排泄分数的增加（p＜0.0001）。远端钠重吸收从78.3±0.8%降至73.2±1.1%，但变化无统计学意义。相比之下，钠缺乏受试者除肾血浆流量从550±13增至625±17毫升/分钟（p＜＜0.0001）外，无显著变化。整个研究过程中肾小球滤过率保持不变。这些结果表明，利尿和利钠反应由近端和远端肾小管部位的DA1受体介导。钠缺乏时DA1利钠反应减弱提示肾小管细胞DA1机制受到直接抑制或肾脏内非多巴胺能代偿性稳态机制被激活。
