给药时间和性别对利尿剂利钠、利尿和钾利尿作用的影响。

IF 3.7 2区 医学 Q1 PHYSIOLOGY American Journal of Physiology-renal Physiology Pub Date : 2023-03-01 DOI:10.1152/ajprenal.00296.2022
Pritha Dutta, Mehrshad Sadria, Anita T Layton
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引用次数: 2

摘要

在许多物种中,肾功能和血压的性别差异已被广泛描述。血压在睡眠时下降,在清晨达到峰值。同样,肾小球滤过率、滤过电解质负荷、尿量和尿排泄都表现出明显的昼夜节律,这在一定程度上反映了生物钟基因对肾转运蛋白的调节。这种调节是两性二态的;因此,性别和时间并不是肾脏功能和血压的两个独立调节者。本研究的目的是评估性别和给药时间对环、噻嗪和K+保留利尿剂的利钠和利尿作用的影响,这些利尿剂是高血压的常用治疗药物。袢利尿剂抑制粗升肢顶端膜上的Na+-K+- 2cl -共转运蛋白,噻嗪类利尿剂抑制远曲小管上的Na+- cl -共转运蛋白,K+保留利尿剂抑制连接小管和集管上的上皮Na+通道。我们使用小鼠肾脏功能的性别和时间特异性计算模型模拟Na+转运体抑制。模拟结果突出了药物反应的显著性别和时间差异。袢利尿剂在活跃期诱导较大的利钠和利尿作用。噻嗪类利尿剂的利钠和利尿作用表现出性别和时间差异,而K+保留利尿剂的这些作用仅在女性中表现出显著的时间差异。利尿作用取决于利尿剂的种类和给药时间。目前的计算模型可以成为时间疗法的有用工具,可以根据人体的昼夜节律调整给药时间,以优化药物效果。性别影响心血管疾病,急性心血管事件发生的时间表现出昼夜节律。肾功能也表现出性别差异和昼夜节律。利尿剂是一种常见的针对肾脏的高血压治疗药物,它的利钠和利尿作用在两性之间有何不同?这些影响在白天是如何变化的呢?为了回答这些问题,我们进行了计算机模拟来评估环、噻嗪和K+保留利尿剂的效果。
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Influence of administration time and sex on natriuretic, diuretic, and kaliuretic effects of diuretics.

Sex differences in renal function and blood pressure have been widely described across many species. Blood pressure dips during sleep and peaks in the early morning. Similarly, glomerular filtration rate, filtered electrolyte loads, urine volume, and urinary excretion all exhibit notable diurnal rhythms, which reflect, in part, the regulation of renal transporter proteins by circadian clock genes. That regulation is sexually dimorphic; as such, sex and time of day are not two independent regulators of kidney function and blood pressure. The objective of the present study was to assess the effect of sex and administration time on the natriuretic and diuretic effects of loop, thiazide, and K+-sparing diuretics, which are common treatments for hypertension. Loop diuretics inhibit Na+-K+-2Cl- cotransporters on the apical membrane of the thick ascending limb, thiazide diuretics inhibit Na+-Cl- cotransporters on the distal convoluted tubule, and K+-sparing diuretics inhibit epithelial Na+ channels on the connecting tubule and collecting duct. We simulated Na+ transporter inhibition using sex- and time-of-day-specific computational models of mouse kidney function. The simulation results highlighted significant sex and time-of-day differences in the drug response. Loop diuretics induced larger natriuretic and diuretic effects during the active phase. The natriuretic and diuretic effects of thiazide diuretics exhibited sex and time-of-day differences, whereas these effects of K+-sparing diuretics exhibited a significant time-of-day difference in females only. The kaliuretic effect depended on the type of diuretics and time of administration. The present computational models can be a useful tool in chronotherapy, to tailor drug administration time to match the body's diurnal rhythms to optimize the drug effect.NEW & NOTEWORTHY Sex influences cardiovascular disease, and the timing of onset of acute cardiovascular events exhibits circadian rhythms. Kidney function also exhibits sex differences and circadian rhythms. How do the natriuretic and diuretic effects of diuretics, a common treatment for hypertension that targets the kidneys, differ between the sexes? And how do these effects vary during the day? To answer these questions, we conducted computer simulations to assess the effects of loop, thiazide, and K+-sparing diuretics.

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来源期刊
CiteScore
8.40
自引率
7.10%
发文量
154
审稿时长
2-4 weeks
期刊介绍: The American Journal of Physiology - Renal Physiology publishes original manuscripts on timely topics in both basic science and clinical research. Published articles address a broad range of subjects relating to the kidney and urinary tract, and may involve human or animal models, individual cell types, and isolated membrane systems. Also covered are the pathophysiological basis of renal disease processes, regulation of body fluids, and clinical research that provides mechanistic insights. Studies of renal function may be conducted using a wide range of approaches, such as biochemistry, immunology, genetics, mathematical modeling, molecular biology, as well as physiological and clinical methodologies.
期刊最新文献
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