Shirley D G, Skinner J, Walter S J
Br J Pharmacol. 1987 Jul;91(3):693-9. doi: 10.1111/j.1476-5381.1987.tb11264.x.
The influence of dietary potassium on the natriuretic effect of hydrochlorothiazide was investigated in conscious rats which had access to 0.46 M NaCl solution; the intake of saline was used as an index of the natriuresis. Control rats drank very little saline (less than 1 mmol 24 h-1), whereas animals given hydrochlorothiazide in the food (35 mg kg-1 dry weight) increased their saline intake to approximately 10 mmol 24 h-1. In a third group of rats, on a high-potassium diet (360 mmol kg-1 dry weight vs 60 mmol kg-1 dry weight), the same dose of hydrochlorothiazide increased the saline intake to only 2 mmol 24 h-1. In order to investigate the renal mechanisms involved in these effects, animals were anaesthetized and prepared for micropuncture. Collections were made from late surface convolutions of proximal tubules and from early and late regions of distal tubules. Total glomerular filtration rate, single-nephron filtration rate, and the delivery of sodium to the end of the proximal tubule and to the beginning of the distal tubule were similar in the three groups of rats. In rats on a normal diet, hydrochlorothiazide treatment was associated with an increased delivery of sodium to the end of the distal tubule. No such increase was seen in thiazide-treated rats on a high potassium intake. It is concluded that a high potassium intake reduces the natriuretic effect of hydrochlorothiazide as a result of interference with thiazide-induced inhibition of sodium reabsorption in the distal tubule. The effect of potassium does not depend on changes in sodium handling in other nephron segments. The possible roles of aldosterone and distal tubular potassium secretion in mediating this effect are discussed.
在可自由饮用0.46 M NaCl溶液的清醒大鼠中，研究了饮食中钾对氢氯噻嗪利钠作用的影响；盐摄入量用作利钠作用的指标。对照大鼠饮用的盐水很少（少于1 mmol 24 h-1），而在食物中给予氢氯噻嗪（35 mg kg-1干重）的动物，其盐摄入量增加到约10 mmol 24 h-1。在第三组大鼠中，给予高钾饮食（360 mmol kg-1干重对比60 mmol kg-1干重），相同剂量的氢氯噻嗪使盐摄入量仅增加到2 mmol 24 h-1。为了研究这些作用所涉及的肾脏机制，将动物麻醉并准备进行微穿刺。从近端小管的晚期表面卷曲以及远端小管的早期和晚期区域进行收集。三组大鼠的总肾小球滤过率、单肾单位滤过率以及钠输送到近端小管末端和远端小管起始处的情况相似。在正常饮食的大鼠中，氢氯噻嗪治疗与钠输送到远端小管末端增加有关。在高钾摄入的噻嗪类治疗大鼠中未观察到这种增加。得出的结论是，高钾摄入会降低氢氯噻嗪的利钠作用，这是由于干扰了噻嗪类诱导的远端小管钠重吸收抑制作用。钾的作用不依赖于其他肾单位节段钠处理的变化。讨论了醛固酮和远端小管钾分泌在介导这种作用中的可能作用。
