Jaton T, Thonney M, Gouyon J B, Guignard J P
Service de Pédiatrie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Life Sci. 1992;50(3):195-202. doi: 10.1016/0024-3205(92)90272-q.
The renal effects of dopexamine, a new dopaminergic agonist with marked beta 2-adrenergic agonist properties, but no alpha-adrenergic effect, has been studied in 8 newborn New Zealand rabbits, whose renal functional characteristics show close similarities with those of premature infants. Six animals were used as controls. After a control period, dopexamine was infused intravenously at a rate of 4 micrograms/kg per min and after a wash-out period, at 10 micrograms/kg per min. The renal effects of dopamine were studied in similar conditions. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined by inulin and para-aminohippuric acid clearances, respectively. Dopexamine, 4 micrograms/kg per min, did not induce changes in cardiovascular and renal hemodynamics or in renal functions. At 10 micrograms/kg per min, a significant increase in urine flow rate (25 +/- 5%; p less than 0.01), urine sodium excretion (77 +/- 17%; p less than 0.01) and fractional sodium excretion (69 +/- 25%; p less than 0.05) was observed. The GFR, RPF and renal vascular resistance (RVR) were not affected. Heart rate increased slightly but significantly (8 +/- 3%; p less than 0.05), without change in mean blood pressure (MBP). Dopamine, 4 micrograms/kg per min, decreased slightly albeit significantly MBP (3 +/- 1%; p less than 0.05). At 10 micrograms/kg per min the only renal effect was a significant increase in RVR (19 +/- 6%; p less than 0.02). The different actions of these two dopaminergic agonists in this immature model could be explained by their respective ability to activate electively the adrenergic and dopaminergic peripheral receptors. The natriuretic and diuretic effect of dopexamine in normal immature rabbits, in the absence of changes in RPF or GFR is probably mediated by a direct action of this agent on dopaminergic tubular receptors. Failure of these two drugs to increase RPF may be related to an immaturity of the dopaminergic vascular receptors.
多培沙明是一种新型多巴胺能激动剂，具有显著的β2 -肾上腺素能激动剂特性，但无α -肾上腺素能效应。本研究观察了其对8只新西兰新生兔的肾脏影响，这些新生兔的肾功能特征与早产儿极为相似。6只动物作为对照。在对照期后，以每分钟4微克/千克的速率静脉输注多培沙明，经过洗脱期后，以每分钟10微克/千克的速率输注。在相似条件下研究了多巴胺的肾脏效应。分别通过菊粉清除率和对氨基马尿酸清除率测定肾小球滤过率（GFR）和肾血浆流量（RPF）。每分钟4微克/千克的多培沙明未引起心血管和肾脏血流动力学或肾功能的变化。在每分钟10微克/千克时，观察到尿流率显著增加（25±5%；P＜0.01）、尿钠排泄增加（77±17%；P＜0.01）和钠排泄分数增加（69±25%；P＜0.05）。GFR、RPF和肾血管阻力（RVR）未受影响。心率略有但显著增加（8±3%；P＜0.05），平均血压（MBP）无变化。每分钟4微克/千克的多巴胺使MBP略有但显著降低（3±1%；P＜0.05）。在每分钟10微克/千克时，唯一的肾脏效应是RVR显著增加（19±6%；P＜0.02）。在这个未成熟模型中，这两种多巴胺能激动剂的不同作用可能是由于它们各自选择性激活肾上腺素能和多巴胺能外周受体的能力不同。多培沙明在正常未成熟兔中产生的利钠和利尿作用，在RPF或GFR无变化的情况下，可能是该药物对肾小管多巴胺能受体的直接作用介导的。这两种药物未能增加RPF可能与多巴胺能血管受体不成熟有关。
