Sex difference in kidney electrolyte transport III: Impact of low K intake on thiazide-sensitive cation excretion in male and female mice.
Sex difference in kidney electrolyte transport III: Impact of low K intake on thiazide-sensitive cation excretion in male and female mice.
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DOI：
10.1007/s00424-021-02611-5
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Wang T
中科院分区：
文献类型：
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作者：
Xu S;Li J;Yang L;Wang CJ;Liu T;Weinstein AM;Palmer LG;Wang T
我们比较了雄性和雌性小鼠NaCl共转运体（NCC）在适应低钾（LK）饮食中的调节。我们测量了氢氯噻嗪（HCTZ）引起的雄性和雌性小鼠尿量（UV）、肾小球滤过率（GFR）、绝对（ENa， EK）和分数（FENa， FEK）排泄在对照k （CK, 1% KCl）和LK （0.1% KCl）饮食中7天的变化。与之前观察到的一样，在CK中，ncc依赖性的ENa和FENa在雌性中比雄性大。然而，随着LK的增加，hctz诱导的ENa和FENa在雄性中增加，而在雌性中没有增加，消除了CK组NCC功能的性别差异。尽管对HCTZ有很大的利尿和利钠反应，但当动物服用LK时，EK对药物的反应仅略有增加。这表明在这些条件下，远端肾元的k分泌器受到强烈抑制。我们还通过Western blotting检测了lk诱导的Na转运蛋白表达的变化。在CK条件下，雌性表达更多的NCC蛋白。LK在雄性中使总（tNCC）和磷酸化NCC （pNCC）丰度增加了一倍，但对雌性的影响较小。在男性中更大的影响消除了NCC表达的性别依赖性，与肾清除率的功能测量一致。LK摄入没有改变NHE3， NHE2或NKCC2的表达，但减少了裂解（可能是活性）形式的γENaC的数量。LK使女性血浆钾降至比男性低的水平。这些结果表明，雄性比雌性具有更强的ncc介导的对LK摄入的适应。
We compared the regulation of the NaCl cotransporter (NCC) in adaptation to a low-K (LK) diet in male and female mice. We measured hydrochlorothiazide (HCTZ)-induced changes in urine volume (UV), glomerular filtration rate (GFR), absolute (ENa, EK), and fractional (FENa, FEK) excretion in male and female mice on control-K (CK, 1% KCl) and LK (0.1% KCl) diets for 7 days. With CK, NCC-dependent ENa and FENa were larger in females than males as observed previously. However, with LK, HCTZ-induced ENa and FENa increased in males but not in females, abolishing the sex differences in NCC function as observed in CK group. Despite large diuretic and natriuretic responses to HCTZ, EK was only slightly increased in response to the drug when animals were on LK. This suggests that the K-secretory apparatus in the distal nephron is strongly suppressed under these conditions. We also examined LK-induced changes in Na transport protein expression by Western blotting. Under CK conditions females expressed more NCC protein, as previously reported. LK doubled both total (tNCC) and phosphorylated NCC (pNCC) abundance in males but had more modest effects in females. The larger effect in males abolished the sex-dependence of NCC expression, consistent with the measurements of function by renal clearance. LK intake did not change NHE3, NHE2, or NKCC2 expression, but reduced the amount of the cleaved (presumably active) form of γENaC. LK reduced plasma K to lower levels in females than males. These results indicated that males had a stronger NCC-mediated adaptation to LK intake than females.