Olesen O V
J Pharmacol Exp Ther. 1982 Jan;220(1):178-82.
Hydrochlorothiazide (HCTZ)-induced Na requirement was examined in rats fed a standard diet containing 250 mg of HCTZ per kg of food and given a free choice between water and 0.46 M NaCl. HCTZ treatment led to a persistent 8-fold increase of NaCl intake. An increase of the K content of the food from 100 to 600 mmol/kg reduce the NaCl intake by 75%. Maintenance on a high K diet prevented the HCTZ-induced requirement for extra Na and diminished HCTZ-induced loss of body weight and urinary loss of Na. Determinations of lithium clearance (CLi) in unanesthetized rats by using nontoxic doses of lithium was used as a measure of Na clearance at the end of the proximal tubules (CNa prox). The urinary sodium clearance divided by the urinary lithium clearance (CNa/CLi) was used to express the fractional escape of Na from distal reabsorption. In HCTZ-treated rats, maintenance on a high K diet reduced CNa and CNa/CLi. A high potassium intake increased CNa prox, but this effect was least in HCTZ-treated rats. The results show that a high K intake reduced the natriuretic effect of HCTZ. The renal mechanism is presumably a potassium-induced compensatory increase of the reabsorption of Na delivered from the proximal tubules.
研究了氢氯噻嗪（HCTZ）诱导的钠需求，实验用大鼠喂食每千克食物含250毫克HCTZ的标准饮食，并可自由选择饮水和0.46M氯化钠溶液。HCTZ处理导致氯化钠摄入量持续增加8倍。将食物中的钾含量从100mmol/kg增加到600mmol/kg可使氯化钠摄入量减少75%。维持高钾饮食可防止HCTZ诱导的额外钠需求，并减少HCTZ诱导的体重减轻和尿钠流失。通过使用无毒剂量的锂来测定未麻醉大鼠的锂清除率（CLi），以此作为近端小管末端钠清除率（CNa prox）的指标。尿钠清除率除以尿锂清除率（CNa/CLi）用于表示钠从远端重吸收的分数逃逸率。在接受HCTZ治疗的大鼠中，维持高钾饮食可降低CNa和CNa/CLi。高钾摄入可增加CNa prox，但这种作用在接受HCTZ治疗的大鼠中最小。结果表明，高钾摄入可降低HCTZ的利钠作用。其肾脏机制可能是钾诱导近端小管输送的钠重吸收代偿性增加。
