Stadt Melissa, Layton Anita T
Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, Canada.
Department of Biology, University of Waterloo, Waterloo, Ontario, Canada.
Am J Physiol Renal Physiol. 2025 Mar 1;328(3):F406-F417. doi: 10.1152/ajprenal.00222.2024. Epub 2024 Oct 24.
High Na intake has been linked to elevations in blood pressure, whereas K has the opposite effect. The underlying mechanisms involve complex interactions among renal function, fluid volume, fluid-regulatory hormones, vasculature, cardiac function, and the autonomic nervous system. These mechanisms are likely modulated by sex, given the known sex differences in blood pressure regulation and the higher prevalence of hypertension in men. The source of these observed sex differences may be traced to organ and tissue levels, given that kidney function, intrarenal renin-angiotensin system components, renal sympathetic nervous activity, and nitric oxide bioavailability all exhibit sex differences. To assess the functional impact of each of these sex differences, we developed sex-specific computational models to simulate whole-body Na, K, and fluid homeostasis, and the effects on blood pressure. The models describe the interactions among the renal system, cardiovascular system, gastrointestinal system, renal sympathetic nervous system, and renin-angiotensin-aldosterone system. Model simulations suggest that women's attenuated blood pressure response to hypertensive stimuli, including high Na intake, may be largely attributable to the female renal transporter abundance pattern. In addition, we investigated the causal link between high K intake and blood pressure reduction. The models simulate renal response to high K intake, including the immediate gastrointestinal feedforward signals to the kidneys to increase K excretion, and the longer-term response to decrease proximal fractional Na reabsorption and distal K reabsorption. With these assumptions, simulations of high K intake yielded kaliuresis, natriuresis, and a substantial reduction in blood pressure, even when combined with high Na intake. Excessive dietary Na raises blood pressure, whereas a high K diet has the opposite effect. The underlying mechanisms are moderated by sex and involve multiple organs and tissues. How do high K-induced alternations in kidney function lower blood pressure, and how do those mechanisms differ between men and women? To answer these questions, we conducted computer simulations to simulate whole-body fluid and electrolyte homeostasis, and the effects of Na and K intake on blood pressure.
高钠摄入与血压升高有关，而钾则有相反的作用。其潜在机制涉及肾功能、血容量、液体调节激素、血管系统、心脏功能和自主神经系统之间的复杂相互作用。鉴于血压调节中已知的性别差异以及男性高血压患病率较高，这些机制可能受到性别的调节。鉴于肾功能、肾内肾素 - 血管紧张素系统成分、肾交感神经活动和一氧化氮生物利用度均存在性别差异，这些观察到的性别差异的根源可能追溯到器官和组织水平。为了评估这些性别差异各自的功能影响，我们开发了特定性别的计算模型来模拟全身钠、钾和液体稳态以及对血压的影响。这些模型描述了肾脏系统、心血管系统、胃肠道系统、肾交感神经系统和肾素 - 血管紧张素 - 醛固酮系统之间的相互作用。模型模拟表明，女性对高血压刺激（包括高钠摄入）的血压反应减弱可能在很大程度上归因于女性肾转运体丰度模式。此外，我们研究了高钾摄入与血压降低之间的因果关系。这些模型模拟了肾脏对高钾摄入的反应，包括胃肠道向肾脏发出的立即增加钾排泄的前馈信号，以及减少近端钠重吸收和远端钾重吸收的长期反应。基于这些假设，即使与高钠摄入同时存在，高钾摄入的模拟结果也会产生尿钾增多、尿钠增多和血压大幅降低。过量的饮食钠会升高血压，而高钾饮食则有相反的效果。其潜在机制受到性别的调节，涉及多个器官和组织。高钾引起的肾功能改变如何降低血压，以及这些机制在男性和女性之间有何不同？为了回答这些问题，我们进行了计算机模拟，以模拟全身液体和电解质稳态以及钠和钾摄入对血压的影响。
