Wang Bangchen, Sansom Steven C
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center , Omaha, Nebraska.
Am J Physiol Renal Physiol. 2019 May 1;316(5):F970-F973. doi: 10.1152/ajprenal.00614.2018. Epub 2019 Mar 6.
In individuals on a regular "Western" diet, furosemide induces a kaliuresis and reduction in plasma K concentration by inhibiting Na reabsorption in the thick ascending limb of Henle's loop, enhancing delivery of Na to the aldosterone-sensitive distal nephron. In the aldosterone-sensitive distal nephron, the increased Na delivery stimulates K wasting due to an exaggerated exchange of epithelial Na channel-mediated Na reabsorption of secreted K. The effects of furosemide are different in mice fed a high-K, alkaline (HK) diet: the large-conductance Ca-activated K (BK) channel, in conjunction with the BK β-subunit (BK-α/β), mediates K secretion from intercalated cells (IC) of the connecting tubule and collecting ducts. The urinary alkaline load is necessary for BK-α/β-mediated K secretion in HK diet-fed mice. However, furosemide acidifies the urine by increasing vacuolar ATPase expression and acid secretion from IC, thereby inhibiting BK-α/β-mediated K secretion and sparing K. In mice fed a low-Na, high-K (LNaHK) diet, furosemide causes a greater increase in plasma K concentration and reduction in K excretion than in HK diet-fed mice. Micropuncture of the early distal tubule of mice fed a LNaHK diet, but not a regular or a HK diet, reveals K secretion in the thick ascending limb of Henle's loop. The sites of action of K secretion in individuals consuming a high-K diet should be taken into account when diuretic agents known to waste K with low or moderate K intakes are prescribed.
在日常遵循“西方”饮食的个体中，呋塞米通过抑制亨氏袢升支粗段对钠的重吸收，促使钾随尿排出并降低血浆钾浓度，增加到达醛固酮敏感远端肾单位的钠量。在醛固酮敏感远端肾单位，由于上皮钠通道介导的钠重吸收与分泌钾的交换过度，增加的钠输送会刺激钾的流失。呋塞米对喂食高钾、碱性（HK）饮食小鼠的影响有所不同：大电导钙激活钾（BK）通道与BKβ亚基（BK-α/β）共同介导连接小管和集合管闰细胞（IC）的钾分泌。尿碱性负荷对于喂食HK饮食小鼠中BK-α/β介导的钾分泌是必需的。然而，呋塞米通过增加空泡型ATP酶表达和IC的酸分泌使尿液酸化，从而抑制BK-α/β介导的钾分泌并保留钾。在喂食低钠、高钾（LNaHK）饮食的小鼠中，呋塞米导致血浆钾浓度升高幅度更大，钾排泄减少幅度比喂食HK饮食的小鼠更大。对喂食LNaHK饮食而非常规或HK饮食小鼠的早期远端小管进行微穿刺，发现亨氏袢升支粗段有钾分泌。当开具有已知在低钾或中等钾摄入量时会导致钾流失的利尿剂处方时，应考虑食用高钾饮食个体中钾分泌的作用位点。
