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Clinical importance of potassium intake and molecular mechanism of potassium regulation.

ABSTRACT:

Introduction

Potassium (K⁺) intake is intrinsically linked to blood pressure. High-K⁺ intake decreases hypertension and associated lower mortality. On the other hand, hyperkalemia causes sudden death with fatal cardiac arrhythmia and is also related to higher mortality. Renal sodium (Na⁺)-chloride (Cl^‒) cotransporter (NCC), expressed in the distal convoluted tubule, is a key molecule in regulating urinary K⁺ excretion. K⁺ intake affects the activity of the NCC, which is related to salt-sensitive hypertension. A K⁺-restrictive diet activates NCC, and K⁺ loading suppresses NCC. Hyperpolarization caused by decreased extracellular K⁺ concentration ([K⁺]_ex) increases K⁺ and Cl^‒ efflux, leading to the activation of Cl^‒-sensitive with-no-lysine (WNK) kinases and their downstream molecules, including STE20/SPS1-related proline/alanine-rich kinase (SPAK) and NCC.

Results

We investigated the role of the ClC-K2 Cl^‒ channel and its β-subunit, barttin, using barttin hypomorphic (Bsnd^neo/neo) mice and found that these mice did not show low-K⁺-induced NCC activation and salt-sensitive hypertension. Additionally, we discovered that the suppression of NCC by K⁺ loading was regulated by another mechanism, whereby tacrolimus (a calcineurin [CaN] inhibitor) inhibited high-K⁺-induced NCC dephosphorylation and urinary K⁺ excretion. The K⁺ loading and the tacrolimus treatment did not alter the expression of WNK4 and SPAK. The depolarization induced by increased [K⁺]_ex activated CaN, which dephosphorylates NCC.

Conclusions

We concluded that there were two independent molecular mechanisms controlling NCC activation and K⁺ excretion. This review summarizes the clinical importance of K⁺ intake and explains how NCC phosphorylation is regulated by different molecular mechanisms between the low- and the high-K⁺ condition.

SUBMITTER: Nomura N

PROVIDER: S-EPMC6746677 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Clinical importance of potassium intake and molecular mechanism of potassium regulation.

Nomura Naohiro N Shoda Wakana W Uchida Shinichi S

Clinical and experimental nephrology 20190717 10

<h4>Introduction</h4>Potassium (K+) intake is intrinsically linked to blood pressure. High-K+ intake decreases hypertension and associated lower mortality. On the other hand, hyperkalemia causes sudden death with fatal cardiac arrhythmia and is also related to higher mortality. Renal sodium (Na+)-chloride (Cl‒) cotransporter (NCC), expressed in the distal convoluted tubule, is a key molecule in regulating urinary K+ excretion. K+ ...[more]

PMID: 31317362

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Project description:BackgroundHigh blood pressure is the leading cause of cardiovascular disease worldwide. The prevalence of high blood pressure is steadily rising as the population grows amongst older adults with the ageing population. Therapeutical treatments are widely available to decrease blood pressures, in addition to many lifestyle options, such as dietary changes and exercise. There is a marked preference amongst patients, as reiterated by Hypertension Canada, for more research into non-therapeutic methods for controlling blood pressure or to reduce the burden of taking many pills to control high blood pressure. Indeed, effective options do exist, especially with diet, specifically decreasing sodium and increasing potassium intake. Current public health outreach primarily focusses on sodium intake, even though potassium intake remains low in the Western world. Excellent data exist in published research that increasing potassium intake, either via dietary modification or supplements, reduces blood pressure and reduces risk of cardiovascular outcomes such as stroke. However, the advice most often provided by medical professionals is to 'eat more fruits and vegetables' which has little impact on patient outcomes.MethodsWe propose to do a clinical trial in two stages with an adaptive trial design. In the first stage, participants with high blood pressure and proven low potassium intake (measured on the basis of a 24-h urine collection) will get individually tailored dietary advice, reinforced by weekly supportive phone/email support. At 4 weeks, if there has not been a measured increase in potassium intake, participants will be prescribed an additional potassium supplement. Testing will be conducted again at 8 weeks, to confirm the efficacy of the potassium supplement. Final measurements will be planned at 52 weeks to observe and measure the persistence of the effect of diet or additional supplement. Concurrent measurements of sodium intake, blood pressure, participant satisfaction, and safety measures will also be done.DiscussionThe results of the study will help determine the most effective method of increasing potassium intake, thus reducing blood pressure and need for blood pressure-lowering medicines, and at the same time potentially increasing participant satisfaction. The current guidelines recommend changes in diet, not a potassium supplement, to increase potassium intake; hence, the two-stage design will only add supplements if the most rigorous dietary advice does not work.Trial registrationThis study has been registered on ClinicalTrials.gov NCT03809884 . Registered on January 18, 2019.

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Clinical importance of potassium intake and molecular mechanism of potassium regulation.

Introduction

Results

Conclusions

Publications

Clinical importance of potassium intake and molecular mechanism of potassium regulation.

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