Girbes A R, Smit A J, Meijer S, Reitsma W D
Department of Internal Medicine, University Hospital Groningen, The Netherlands.
Nephron. 1990;56(2):179-85. doi: 10.1159/000186129.
The effects of fenoldopam (FD), a selective dopamine-1 (DA1) agonist in doses from 0.05 to 0.50 micrograms/kg/min and of the aselective dopamine antagonist metoclopramide (MCP) on blood pressure (BP), sodium excretion and renal hemodynamics were investigated in 10 healthy volunteers. During FD infusion the diastolic BP fell 9 mm Hg with a rise in heart rate. During combined infusion of FD and MCP no changes in BP occurred. Effective renal plasma flow rose for all doses of FD with a maximal increase of 36% and was not influenced by MCP infusion. Glomerular filtration rate remained unchanged. FD induced an increase in sodium and calcium excretion compared to placebo study, which was abolished by MCP. A marked rise of plasma renin activity during FD infusion was noted, blunted by MCP. MCP induced a marked increase of aldosterone, sustained, but blunted, during subsequent FD infusion, suggesting a DA1-mediated influence on aldosterone secretion. During infusion of FD alone, an increased urinary dopamine excretion was observed. We conclude that FD induces: (1) systemic and renal vasodilation and (2) natriuresis by direct stimulation of DA1 receptors in the proximal tubule, which is (partially) counteracted by a rise of plasma renin activity and subsequently of aldosterone.
在10名健康志愿者中研究了选择性多巴胺-1（DA1）激动剂非诺多泮（FD）以0.05至0.50微克/千克/分钟的剂量以及非选择性多巴胺拮抗剂甲氧氯普胺（MCP）对血压（BP）、钠排泄和肾血流动力学的影响。在输注FD期间，舒张压下降9毫米汞柱，心率上升。在联合输注FD和MCP期间，血压没有变化。所有剂量的FD均可使有效肾血浆流量增加，最大增幅为36%，且不受MCP输注的影响。肾小球滤过率保持不变。与安慰剂研究相比，FD可使钠和钙排泄增加，而MCP可消除这种增加。在输注FD期间，血浆肾素活性显著升高，MCP可使其减弱。MCP可使醛固酮显著增加，在随后输注FD期间持续存在但有所减弱，提示DA1对醛固酮分泌有介导作用。在单独输注FD期间，观察到尿多巴胺排泄增加。我们得出结论，FD可诱导：（1）全身和肾血管舒张；（2）通过直接刺激近端小管中的DA1受体导致利钠作用，而血浆肾素活性随后升高以及醛固酮升高可（部分）抵消这种作用。
