Potassium homeostasis: sensors, mediators, and targets

McDonough, Alicia A.; Fenton, Robert A.

doi:10.1007/s00424-022-02718-3

Cited by 35 publications

(55 citation statements)

References 167 publications

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“…The benefit of increasing dietary potassium has also gained interest ( McDonough et al, 2017 ; Staruschenko, 2018 ; McDonough and Fenton, 2022 ). The Dietary Approaches to Stop Hypertension (DASH) diet, a US-based multi-center RCT ( Akita et al, 2003 ), along with other studies, demonstrated that elevated potassium (K + ) intake reduces BP in adults with HTN and is associated with a lower risk of death and cardiovascular events ( O'Donnell et al, 2014 ; Terker et al, 2015 ; Pechère-Bertschi and Burnier, 2004 ).…”

Section: Treatment Of Salt-sensitive Htnmentioning

confidence: 99%

“…No Characterized by to increase in CO and cardiac mass due to volume expansion, proteinuria, glomerulosclerosis and endothelial dysfunction (Klanke et al, 2008;Iyer et al, 2010) Increases SNS and the RAAS activity (Sawamura and Nakada, 1996) Dahl salt-sensitive rat model No Induces HTN by increasing sodium retention and proteinuria when fed with high salt diets (Dahl et al, 1962;Dahl et al, 1963;Khan et al, 2012) Promotes endothelial dysfunction, glomerulosclerosis and cardiac hypertrophy and fibrosis (Raij et al, 1984;Hayakawa et al, 1997;Yu et al, 2003) Triggers T cell and macrophage infiltration in the cortex and medulla (Hayakawa et al, 1997;Mattson et al, 2006 The benefit of increasing dietary potassium has also gained interest (McDonough et al, 2017;Staruschenko, 2018;McDonough and Fenton, 2022). The Dietary Approaches to Stop Hypertension (DASH) diet, a US-based multi-center RCT (Akita et al, 2003), along with other studies, demonstrated that elevated potassium (K + ) intake reduces BP in adults with HTN and is associated with a lower risk of death and cardiovascular events (O'Donnell et al, 2014;Terker et al, 2015;Pechère-Bertschi and Burnier, 2004).…”

Section: Nomentioning

confidence: 99%

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Pathophysiology and genetics of salt-sensitive hypertension

Maaliki

Itani

2022

Front. Physiol.

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Most hypertensive cases are primary and heavily associated with modifiable risk factors like salt intake. Evidence suggests that even small reductions in salt consumption reduce blood pressure in all age groups. In that regard, the ACC/AHA described a distinct set of individuals who exhibit salt-sensitivity, regardless of their hypertensive status. Data has shown that salt-sensitivity is an independent risk factor for cardiovascular events and mortality. However, despite extensive research, the pathogenesis of salt-sensitive hypertension is still unclear and tremendously challenged by its multifactorial etiology, complicated genetic influences, and the unavailability of a diagnostic tool. So far, the important roles of the renin-angiotensin-aldosterone system, sympathetic nervous system, and immune system in the pathogenesis of salt-sensitive hypertension have been studied. In the first part of this review, we focus on how the systems mentioned above are aberrantly regulated in salt-sensitive hypertension. We follow this with an emphasis on genetic variants in those systems that are associated with and/or increase predisposition to salt-sensitivity in humans.

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Section: Treatment Of Salt-sensitive Htnmentioning

confidence: 99%

Section: Nomentioning

confidence: 99%

Pathophysiology and genetics of salt-sensitive hypertension

Maaliki

Itani

2022

Front. Physiol.

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“…Identifying all the K + regulatory mechanisms remains an open area of research [1]. For example, following a significant elevation in total body K + , how does the body September 25, 2022 4/28 safely get rid of the excess K + without significantly, and potentially dangerously, raising extracellular K + levels?…”

Section: Feedback and Feedforward Controlsmentioning

confidence: 99%

“…For example, following a significant elevation in total body K + , how does the body September 25, 2022 4/28 safely get rid of the excess K + without significantly, and potentially dangerously, raising extracellular K + levels? One hypothesized mechanism is muscle-kidney cross talk, whereby intracellular K + concentration of skeletal muscle cells can directly affect urine K + excretion without first causing changes in extracellular K + concentration [1,14,19].…”

Section: Feedback and Feedforward Controlsmentioning

confidence: 99%

A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls

Stadt

Leete

Devinyak

2022

Preprint

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Maintaining normal potassium (K+) concentration in the extra- and intracellular fluid is critical for cell function. K+ homeostasis is achieved by ensuring proper distribution between extra- and intracellular fluid compartments and by matching K+ excretion with intake. The Na+-K+-ATPase pump facilitates K+ uptake into the skeletal muscle, where most K+ is stored. Na+-K+-ATPase activity is stimulated by insulin and aldosterone. The kidneys regulate long term K+ regulation by controlling the amount of K+ excreted through urine. Renal handling of K+ is mediated by a number of regulatory mechanisms, including an aldosterone-mediated feedback control, in which high extracellular K+ concentration stimulates aldosterone secretion which enhances urine K+ excretion, and a gastrointestinal feedforward control mechanism, in which dietary K+ intake increases K+ excretion. Recently, a muscle-kidney cross talk signal has been hypothesized, where the K+ concentration in skeletal muscle cells directly affects urine K+ excretion, without changes in extracellular K+ concentration. To understand how these mechanisms coordinate under different K+ challenges, we have developed a compartmental model of whole-body K+ regulation. The model represents the intra- and extracellular fluid compartments in a human (male) as well as a detailed kidney compartment. We included (i) the gastrointestinal feedforward control mechanism, (ii) the effect of insulin, and (iii) aldosterone on Na+-K+-ATPase K+ uptake, and (iv) aldosterone stimulation of renal K+ secretion. We used this model to investigate the impact of regulatory mechanisms on K+ homeostasis. Model predictions showed how the regulatory mechanisms synthesize to ensure that the extra- and intracellular fluid K+ concentrations remain in normal range in times of K+ loading and fasting. Additionally, we predict that without the hypothesized muscle-kidney cross talk signal, the model was unable to predict a return to normal extracellular K+ concentration after a period of high K+ loading or depletion.

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“…Hummler et al examine glucocorticoid signaling in kidney and adrenal gland [ 16 ], while Feraille and Hoorn analyze the current state of understanding how renal handling of water controls water balance [ 6 ]. McDonough and Fenton review mechanisms of extrarenal and renal sensing of potassium and its transport in the kidney [ 9 ] followed by a discussion by Pearce, Nesterov, and Korbmacher on the function of the distal segments of the nephron in sodium transport [ 10 ].…”

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confidence: 99%