Stokes G S, Monaghan J C, Pillai D N
Department of Clinical Pharmacology, Royal North Shore Hospital, St. Leonards, NSW, Australia.
J Hypertens. 1997 Jul;15(7):761-8. doi: 10.1097/00004872-199715070-00008.
To investigate the possible role played by endogenous dopamine as a modulator of renal sodium (Na+) reabsorption after a combined Na+ and volume load.
A randomized placebo-controlled study.
Ten healthy volunteers and four hypertensive patients were subjected to intravenous infusions of 21 0.9% saline (308 mmol Na+) administered from 1000 to 1300 h after oral administration of placebo or of carbidopa, a dopamine decarboxylase inhibitor.
Studies on control subjects after placebo showed that natriuresis occurred during the 6 h after commencement of the saline infusion, with falls in plasma albumin concentration, plasma renin activity and plasma aldosterone concentration; in comparison with results of mock infusion (6 mmol Na+) there was no change in the urinary excretion of dopamine and noradrenaline (In their free or conjugated forms). There was, however, a marked surge in excretion of urinary conjugated dopamine and in the dopamine: noradrenaline ratio from 1300 to 1600 h, after either type of infusion. Administration of carbidopa before the saline infusion resulted in a marked decrease in excretion of urinary free dopamine, but had no effect on the surge in excretion of urinary conjugated dopamine. Saline infusion decreased proximal fractional Na+ reabsorption. Administration of carbidopa delayed but did not prevent this decrease. The effects of saline infusion and of carbidopa on the urinary excretion of dopamine and noradrenaline from hypertensive patients were similar to those observed with the healthy volunteers.
These findings indicate that volume expansion by intravenous saline infusion has no appreciable effect on the urinary free dopamine excretion from normal or hypertensive humans; with any apparent increase, it is important to exclude the possibility of conversion of conjugates to free dopamine in vitro. Furthermore, that carbidopa administration did not inhibit the afternoon surge of conjugated dopamine suggests that administration of carbidopa is deficient as a tool to investigate the functional role of the renal dopamine system.
研究内源性多巴胺在钠和容量负荷联合作用后作为肾钠重吸收调节剂可能发挥的作用。
一项随机安慰剂对照研究。
10名健康志愿者和4名高血压患者在口服安慰剂或多巴胺脱羧酶抑制剂卡比多巴后,于1000至1300时接受静脉输注21次0.9%盐水(308 mmol钠)。
安慰剂治疗后对对照受试者的研究表明,在盐水输注开始后的6小时内出现利钠作用,同时血浆白蛋白浓度、血浆肾素活性和血浆醛固酮浓度下降;与模拟输注(6 mmol钠)的结果相比,多巴胺和去甲肾上腺素(游离或结合形式)的尿排泄量没有变化。然而,在任何一种输注后,从1300至1600时,尿结合多巴胺排泄量和多巴胺:去甲肾上腺素比值均显著升高。在盐水输注前给予卡比多巴导致尿游离多巴胺排泄量显著降低,但对尿结合多巴胺排泄量的升高没有影响。盐水输注降低了近端钠分数重吸收。给予卡比多巴延迟但未阻止这种降低。盐水输注和卡比多巴对高血压患者多巴胺和去甲肾上腺素尿排泄的影响与健康志愿者观察到的相似。
这些发现表明,静脉输注盐水导致的容量扩张对正常或高血压人群的尿游离多巴胺排泄没有明显影响;如果有任何明显增加,重要的是排除体外结合物转化为游离多巴胺的可能性。此外,给予卡比多巴并未抑制下午结合多巴胺的激增,这表明卡比多巴作为研究肾多巴胺系统功能作用的工具存在不足。