Christensen S, Petersen J S, Steiness E, Andreasen F
J Pharmacol Exp Ther. 1987 Jun;241(3):987-93.
The dose-response relationship for the diuretic effect of furosemide, given as i.v. bolus injections (0.1-480 mg/kg) was investigated by clearance technique in conscious rats. By measuring the renal Li clearance, the effects on proximal and distal nephron segments were separated, and peak responses were correlated to the maximal excretion rate of furosemide in the urine. At the highest dose of furosemide, fractional Na excretion was increased from 1 to 19%, due to inhibition of fractional proximal Na reabsorption from 65 to 40% and fractional distal Na reabsorption from 97 to 57%. Furosemide inhibition of fractional proximal Na reabsorption showed a maximum at intermediate doses (7.5 mg/kg), whereas there was no maximum for the inhibition of distal fractional Na reabsorption. The natriuretic response was shorter than expected from the decline in furosemide excretion due to an abrupt fall in glomerular filtration rate and a rapid normalization of proximal fractional Na reabsorption. It is suggested that the maintenance of a normal delivery of tubular fluid to the distal nephron during furosemide-induced volume contraction may be due to inhibition of proximal tubular reabsorption.
通过清除技术，在清醒大鼠中研究了静脉推注速尿（0.1 - 480 mg/kg）利尿作用的剂量 - 反应关系。通过测量肾脏锂清除率，分离了对近端和远端肾单位节段的影响，并将峰值反应与速尿在尿液中的最大排泄率相关联。在速尿的最高剂量下，由于近端钠重吸收分数从65%抑制到40%，远端钠重吸收分数从97%抑制到57%，钠排泄分数从1%增加到19%。速尿对近端钠重吸收分数的抑制在中等剂量（7.5 mg/kg）时达到最大值，而对远端钠重吸收分数的抑制没有最大值。由于肾小球滤过率突然下降和近端钠重吸收分数迅速恢复正常，利钠反应比根据速尿排泄下降预期的要短。有人认为，速尿诱导容量收缩期间维持向远端肾单位正常输送肾小管液可能是由于抑制近端肾小管重吸收。
