Dietary Potassium Supplementation Research Articles

Dietary Potassium Supplementation Reduces Chronic Kidney Lesions Independent of Blood Pressure in Deoxycorticosterone-Acetate and High Sodium Chloride-Treated Mice

We have previously shown that an excess of deoxycorticosterone acetate and high sodium chloride intake (DOCA/salt) in one-renin gene mice induces a high urinary Na/K ratio, hypokalemia, and cardiac and renal hypertrophy in the absence of hypertension. Dietary potassium supplementation prevents DOCA/salt-induced pathological processes. In the present study, we further study whether DOCA/salt-treated mice progressively develop chronic inflammation and fibrosis in the kidney and whether dietary potassium supplementation can reduce the DOCA/salt-induced renal pathological process. Results showed that (1) long-term DOCA/salt-treated one-renin gene mice developed severe kidney injuries including tubular/vascular hypertrophy, mesangial/interstitial/perivascular fibrosis, inflammation (lymphocyte’s immigration), proteinuria, and high serum creatinine in the absence of hypertension; (2) there were over-expressed mRNAs of plasminogen activator inhibitor-1 (PAI-1), fibronectin, collagen type I and III, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP1), transforming growth factor-β (TGF-β), tumor necrosis factor-alpha (TNF-α), osteopontin, Nuclear factor kappa B (NF-κB)/P65, and intercellular adhesion molecule (ICAM)-1; and (3) dietary potassium supplementation normalized urinary Na/K ratio, hypokalemia, proteinuria, and serum creatinine, reduced renal hypertrophy, inflammations, and fibrosis, and down-regulated mRNA expression of fibronectin, Col-I and III, TGF-β, TNF-α, osteopontin, and ICAM without changes in the blood pressure. The results provide new evidence that potassium and sodium may modulate proinflammatory and fibrotic genes, leading to chronic renal lesions independent of blood pressure.

Dietary Potassium and Potassium Supplementation Differentially Affect Plasma Potassium in Patients with CKD

Dietary Potassium and Potassium Supplementation Differentially Affect Plasma Potassium in Patients with CKD

Abstract P300: Blood Pressure Increase Upon High Dietary Potassium Supplementation Is Not Associated With Renal Sodium Retention Or Plasma Volume Expansion

Background: High dietary K + supplementation increases arterial blood pressure in humans and in mice. The mechanisms underlying this unexpected response are still not fully understood. Recent studies in mice reported an activation of the epithelial sodium channel (ENaC) suggesting that renal Na + retention may prominently contribute to the blood pressure increase caused by a high KCl intake. Here, we tested whether a high K + intake causes renal Na + retention and plasma volume expansion. Methods: Na + -replete C57BL/6J mice were subjected to either a normal (0.93%, NK) or a high (5%, HK) KCl or KCitrate diet for up to 14 days. Blood pressure responses to diets and to the additional administration of the ENaC blocker amiloride were measured using radiotelemetry in unrestrained animals. Plasma aldosterone concentrations were quantified by ELISA. Renal Na + retention was assessed by determining urinary Na + excretion. To detect plasma volume expansion, we used a dilution method (Evans blue), determined blood hematocrit, and estimated end diastolic left ventricular volume by echocardiography after 10 days of diet. Results: Both high K + diets increased arterial blood pressure selectively in the dark phase by a nearly identical extent (ΔMAP dark: HKCl +12.7±2.3 mm Hg, p=0.0045, HKCit +12.1±3.0 mm Hg, p=0.0211; ΔMAP light: HKCl -0.2±1.5 mm Hg, p>0.9999, HKCit +2.4±2.2 mm Hg, p=0.9692, 1-way ANOVA, n=7). Even though plasma aldosterone levels were markedly elevated (HKCl 9.9-fold, p=0.0001, HKCit 4.6-fold, p=0.0116, 1-way ANOVA, n=11-12), neither a reduction of renal Na + excretion (urinary [Na + ]/[creatinine] NK 1.0±0.14, HKCl 1.40±0.23, p=0.3873, HKCit 0.94±0.20, p<0.9999, 1-way ANOVA, n=7-13) nor an expansion of plasma volume (NK 898±23 μl, HKCl 918±57 μl, p>0.9999, HKCit 870±62 μl, p>0.9999, 1-way ANOVA, n=6-13) was detected upon the two high K + diets. Amiloride did not normalize arterial blood pressure in mice fed a HKCl or HKCit diet (ΔMAP dark: HKCl +1.2±2.3 mm Hg, p=0.6391 HKCit +2.8±2.0 mm Hg, p=0.2472, 2-tailed paired t-test, n=4). Conclusions: Our findings indicate that excessive K + intake causes elevated blood pressure independent of renal Na + retention and volume expansion in Na + -replete mice.

Dissociation of sodium-chloride cotransporter expression and blood pressure during chronic high dietary potassium supplementation.

Dietary potassium (K+) supplementation is associated with a lowering effect in blood pressure (BP), but not all studies agree. Here, we examined the effects of short- and long-term K+ supplementation on BP in mice, whether differences depend on the accompanying anion or the sodium (Na+) intake and molecular alterations in the kidney that may underlie BP changes. Relative to the control diet, BP was higher in mice fed a high NaCl (1.57% Na+) diet for 7 weeks or fed a K+-free diet for 2 weeks. BP was highest on a K+-free/high NaCl diet. Commensurate with increased abundance and phosphorylation of the thiazide sensitive sodium-chloride-cotransporter (NCC) on the K+-free/high NaCl diet, BP returned to normal with thiazides. Three weeks of a high K+ diet (5% K+) increased BP (predominantly during the night) independently of dietary Na+ or anion intake. Conversely, 4 days of KCl feeding reduced BP. Both feeding periods resulted in lower NCC levels but in increased levels of cleaved (active) α and γ subunits of the epithelial Na+ channel ENaC. The elevated BP after chronic K+ feeding was reduced by amiloride but not thiazide. Our results suggest that dietary K+ has an optimal threshold where it may be most effective for cardiovascular health.

The "FIFTY SHADOWS" of the RALES Trial: Lessons about the Potential Risk of Dietary Potassium Supplementation in Patients with Chronic Kidney Disease.

Hyperkalaemia (HK) is one of the most common electrolyte disorders and a frequent reason for nephrological consultations. High serum potassium (K+) levels are associated with elevated morbidity and mortality, mainly due to life-threatening arrhythmias. In the majority of cases, HK is associated with chronic kidney disease (CKD), or with the use of renin–angiotensin–aldosterone system inhibitors (RAASis) and/or mineral corticoid antagonists (MRAs). These drugs represent the mainstays of treatment in CKD, HF, diabetes, hypertension, and even glomerular diseases, in consideration of their beneficial effect on hard outcomes related to cardiovascular events and CKD progression. However, experiences in relation to the Randomised Aldactone Evaluation Study (RALES) cast a long shadow that extends to the present day, since the increased risk for HK remains a major concern. In this article, we summarise the physiology of K+ homeostasis, and we review the effects of dietary K+ on blood pressure and cardiovascular risk in the general population and in patients with early CKD, who are often not aware of this disease. We conclude with a note of caution regarding the recent publication of the SSaSS trial and the use of salt substitutes, particularly in patients with a limited capacity to increase K+ secretion in response to an exogenous load, particularly in the context of “occult” CKD, HF, and in patients taking RAASis and/or MRAs.

Effects of Chronic Potassium Supplementation and the Accompanying Anion on Blood Pressure

Increased dietary NaCl is associated with higher blood pressure (BP), but dietary potassium supplementation can reduce BP and reduce ‘salt sensitivity’ of BP, improving cardiovascular (CV) outcomes. Rodents fed a high K+ diet often exhibit reduced activity of the sodium-chloride cotransporter NCC, promoting natiuresis, which is a proposed major mechanism for mediating the effects of K+ on BP. However, the role of the accompanying anion during K+ supplementation is a matter of debate, especially considering that low plasma chloride levels are associated with better CV outcomes. Recently, the effect of extreme K+ diets on rodent BP seemed inconsistent with patterns of BP modulation seen in humans. Therefore, the aim of this study was to establish how BP is altered during chronic alteration of dietary potassium intake alongside alternative anions and/or NaCl supplementation. Male mice implanted with telemetric BP monitors were initially normalized to a control diet of NaCl (0.3% Na+) and KCl (1.05% K+), and subsequently maintained on this control diet or a high NaCl (1.57% Na+) (HS) diet for 7 weeks. Subsequently, mice were stratified to receive either a high KCl (5.25% K+) or a high K-citrate (KCit, 5.25% K+) diet during control or high NaCl intake for a subsequent 3 weeks. Finally, a subset of mice were switched to a zero K+ diet with either control or high NaCl level. Throughout the experiment BP, heart rate, activity, urinary ion excretion and plasma Na+/K+/Cl- levels were monitored. 2 weeks 0 K+ diet significantly increased BP, an effect augmented under HS diet. A trend to reduce BP was apparent under control and HS diet during chronic KCl feeding (> effect during resting period), whereas chronic KCit feeding only tended to reduce BP during HS diet. Plasma K+ levels inversely correlated with BP, with chronic KCl inducing a significant increase of 0.5mM, whereas chronic KCit feeding had no significant effect. Plasma aldosterone was also significantly increased 3.5 fold by chronic KCl feeding but not significantly by KCit diet. Total and phosphorylated NCC levels were significantly increased on 0 K+ diet. KCl and KCit feeding during control NaCl or HS intake reduced total NCC levels, whereas phosphorylated NCC was only reduced during chronic KCl intake. All dietary conditions had minimal effect on levels of WNK/SPAK pathway proteins, but αENaC (cleaved/uncleaved) levels were increased, substantially more during KCit feeding. Pendrin abundance was also significantly elevated by KCit feeding. In summary, we show a negative correlation of BP with plasma K+, consistent with human interventional studies. Chronic KCl has a greater ability to lower BP than KCit feeding. This may be related to the ability of KCl to lower NCC phosphorylation, or that large increases in αENaC and pendrin levels during KCit feeding oppose the BP lowering effects of reduced total NCC. As aldosterone levels were increased more with KCl, a differential role of aldosterone also needs to be considered.

Kcnj16 knockout produces audiogenic seizures in the Dahl salt-sensitive rat.

Kir5.1 is an inwardly rectifying potassium (Kir) channel subunit abundantly expressed in the kidney and brain. We previously established the physiologic consequences of a Kcnj16 (gene encoding Kir5.1) knockout in the Dahl salt-sensitive rat (SSKcnj16–/–), which caused electrolyte/pH dysregulation and high-salt diet–induced mortality. Since Kir channel gene mutations may alter neuronal excitability and are linked to human seizure disorders, we hypothesized that SSKcnj16–/– rats would exhibit neurological phenotypes, including increased susceptibility to seizures. SSKcnj16–/– rats exhibited increased light sensitivity (fMRI) and reproducible sound-induced tonic-clonic audiogenic seizures confirmed by electroencephalography. Repeated seizure induction altered behavior, exacerbated hypokalemia, and led to approximately 38% mortality in male SSKcnj16–/– rats. Dietary potassium supplementation did not prevent audiogenic seizures but mitigated hypokalemia and prevented mortality induced by repeated seizures. These results reveal a distinct, nonredundant role for Kir5.1 channels in the brain, introduce a rat model of audiogenic seizures, and suggest that yet-to-be identified mutations in Kcnj16 may cause or contribute to seizure disorders.

Kir5.1‐Mediated Changes in Renin‐Angiotensin‐Aldosterone System Balance in Salt Sensitive Hypertension

Kir5.1 (encoded by Kcnj16 gene) is a member of the inwardly rectifying K+ channel (Kir) family which is expressed in the kidney where it plays an essential role in the maintenance of electrolyte balance and blood pressure control. More specifically, Kir5.1 is highly expressed in the distal convoluted tubule and collecting ducts, also known as the aldosterone‐sensitive distal nephron (ASDN), where it forms a functional channel with Kir4.1. Our previous studies revealed that a knockout of Kcnj16 in the Dahl salt‐sensitive rat (SSKcnj16−/−) results in decreased blood pressure, salt wasting tubulopathy, and hypokalemia (Palygin et al., JCI Insight, 2017). Furthermore, when fed a high salt diet (HS; 4% NaCl), hypokalemia was exacerbated and resulted in mortality of SSKcnj16−/− rats within a few days. Importantly, dietary potassium supplementation or ENaC inhibition with benzamil treatment prevented salt‐induced death. However, specific mechanisms pertaining to cardiorenal abnormalities in SSKcnj16−/− rats and the interaction of Kir4.1/Kir5.1‐mediated potassium transport with the renin‐angiotensin‐aldosterone system (RAAS, a major hormone system that controls fluid and electrolyte balance in ASDN) remains unclear. The main objective of this study was to assess the contribution of RAAS, and specifically aldosterone, in the phenotype observed in SSKcnj16−/− rats. We used mass spectrometry‐based quantification of individual RAAS components to examine whether RAAS hormones were altered in SSKcnj16−/− rats. We found that SSKcnj16−/− rats have drastically elevated serum aldosterone (1878 ± 303 pM for SSKcnj16−/− rats vs 183 ± 35 pM for SS control rats) which becomes significantly attenuated preceding mortality upon introduction of a high salt diet (394 ± 82 pM). All angiotensin derivatives were similarly elevated in SSKcnj16−/− rats, as were RAAS hormone ratios as surrogate measures of angiotensin‐converting enzyme (ACE) activity (Ang II/Ang I), plasma renin activity (PRA, Ang I+Ang II), and primary aldosteronism (AA2‐Ratio). No significant differences in circulating RAAS hormones between male and female rats were observed. Furthermore, blocking aldosterone action with the administration of the potassium‐sparing diuretic, spironolactone (50 mg/kg IP), which is a potent mineralocorticoid receptor antagonist, did not prevent mortalities from a HS diet. Moreover, spironolactone caused 100% mortality within 48 hrs in SSKcnj16−/− (N = 17) but not SS rats during low salt treatment. Blood electrolyte analysis after 24 hrs treatment with spironolactone did not indicate a decline in serum potassium, which was the cause of mortality due to HS intake. Despite this, dietary potassium supplementation (0.36% to 1.41% dietary K+) prevented mortalities due to spironolactone administration in SSKcnj16−/− rats (N = 6). Our data suggest that there is a direct correlation between Kir4.1/Kir5.1‐mediated potassium transport and RAAS function. Our current studies further reveal that hypokalemia due to Kir5.1 deletion results in compensatory RAAS elevation and that supplementation of the diet with high K+ protects from mortality resulting from aldosteronemediated mechanisms.Support or Funding InformationNIHThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Effect of Salt Intake and Potassium Supplementation on Serum Gastrin Levels in Chinese Adults: A Randomized Trial.

Excess dietary salt is strongly correlated with cardiovascular disease, morbidity, and mortality. Conversely, potassium likely elicits favorable effects against cardiovascular disorders. Gastrin, which is produced by the G-cells of the stomach and duodenum, can increase renal sodium excretion and regulate blood pressure by acting on the cholecystokinin B receptor. The aim of our study was to assess the effects of altered salt and potassium supplementation on serum gastrin levels in humans. A total of 44 subjects (38–65 years old) were selected from a rural community in northern China. All subjects were sequentially maintained on a relatively low-salt diet for 7 days (3.0 g/day of NaCl), a high-salt diet for 7 days (18.0 g/day of NaCl), and then a high-salt diet supplemented with potassium for another 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl). The high-salt intake significantly increased serum gastrin levels (15.3 ± 0.3 vs. 17.6 ± 0.3 pmol/L). This phenomenon was alleviated through potassium supplementation (17.6 ± 0.3 vs. 16.5 ± 0.4 pmol/L). Further analyses revealed that serum gastrin was positively correlated with 24 h urinary sodium excretion (r = 0.476, p < 0.001). By contrast, gastrin level was negatively correlated with blood pressure in all dietary interventions (r = −0.188, p = 0.031). The present study indicated that variations in dietary salt and potassium supplementation affected the serum gastrin concentrations in the Chinese subjects.

PP.42.01

Objective: Serum/Glucocorticoid Regulated Kinase 1 (SGK1) plays a significant role in the regulation of renal Na+ reabsorption and K+ secretion as well as blood pressure (BP). The aim of this study was to investigate whether common variants in SGK1 gene are involved in BP responses to dietary sodium intervention or potassium supplementation. Design and method: 344 subjects from 126 families were recruited from rural areas of Northern China. After a 3-day baseline observation, they were sequentially maintained on a 7-day low-sodium diet (3 g of NaCl or 51.3mmol of sodium per day), a 7-day high-sodium diet (18 g of NaCl or 307.8mmol of sodium per day) and a 7-day high-sodium plus potassium supplementation intervention (4.5 g of KCl or 60mmol/d potassium per day). Six single nucleotide polymorphisms (SNPs) were selected from the SGK1 gene. Results: SGK1 SNP rs3813344 was significantly associated with baseline systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) (P = 0.049, 0.015 and 0.018, respectively), and rs9389154 was associated with SBP at baseline (P = 0.040) after adjustment for multiple testing. In addition, rs9376026 was associated with DBP and MAP responses to low-sodium intervention significantly (P = 0.018 and 0.022, respectively). However, no associations between 6 SNPs in the SGK1 gene and BP responses to high-sodium or high-sodium plus potassium-supplementation intervention reached statistical significance. Conclusions: Our study indicates that SGK1 genetic variants may have an important role in BP response to dietary sodium intervention or potassium supplementation and BP regulation.

Effect of Salt Intake and Potassium Supplementation on Urinary Renalase and Serum Dopamine Levels in Chinese Adults

Objective: The aim of our study was to assess the effects of altered salt and potassium intake on urinary renalase and serum dopamine levels in humans. Methods: Forty-two subjects (28-65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day of NaCl), a high-salt diet for an additional 7 days (18.0 g/day of NaCl), and a high-salt diet with potassium supplementation for a final 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl). Results: Urinary renalase excretions were significantly higher during the high-salt diet intervention than during the low-salt diet. During high-potassium intake, urinary renalase excretions were not significantly different from the high-salt diet, whereas they were significantly higher than the low-salt levels. Serum dopamine levels exhibited similar trends across the interventions. Additionally, a significant positive relationship was observed between the urine renalase and serum dopamine among the different dietary interventions. Also, 24-hour urinary sodium excretion positively correlated with urine renalase and serum dopamine in the whole population. Conclusions: The present study indicates that dietary salt intake and potassium supplementation increase urinary renalase and serum dopamine levels in Chinese subjects.

Effect of salt intake and potassium supplementation on brachial-ankle pulse wave velocity in Chinese subjects: an interventional study.

Accumulating evidence has suggested that high salt and potassium might be associated with vascular function. The aim of this study was to investigate the effect of salt intake and potassium supplementation on brachial-ankle pulse wave velocity (PWV) in Chinese subjects. Forty-nine subjects (28-65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day NaCl), a high-salt diet for an additional 7 days (18.0 g/day NaCl), and a high-salt diet with potassium supplementation for a final 7 days (18.0 g/day NaCl+4.5 g/day KCl). Brachial-ankle PWV was measured at baseline and on the last day of each intervention. Blood pressure levels were significantly increased from the low-salt to high-salt diet, and decreased from the high-salt diet to high-salt plus potassium supplementation. Baseline brachial-ankle PWV in salt-sensitive subjects was significantly higher than in salt-resistant subjects. There was no significant change in brachial-ankle PWV among the 3 intervention periods in salt-sensitive, salt-resistant, or total subjects. No significant correlations were found between brachial-ankle PWV and 24-h sodium and potassium excretions. Our study indicates that dietary salt intake and potassium supplementation, at least in the short term, had no significant effect on brachial-ankle PWV in Chinese subjects.

Effects of a high salt intake and potassium supplementation on QT interval dispersion in normotensive healthy subjects.

To evaluate the effects of dietary sodium intake on QT interval dispersion (QTd) in normotensive healthy subjects and assess the protective effects of dietary potassium. Methods All subjects were sequentially maintained on a protocol with a three-day baseline investigation, seven-day low-salt period (3 g/day (d), NaCL), seven-day salt loading period (18 g/d, NaCL) and a seven-day salt loading with potassium supplementation period (4.5 g/d, KCL). On the last day of each period, 24-hour urine samples were collected, the blood pressure values were measured and an electrocardiogram was recorded. The QT interval, QTd and T peak-T end interval (Tp-Te) were subsequently measured and calculated. Patients Sixty-four normotensive subjects, men and women, ranging from 28 to 60 years of age, were enrolled. Results There were no great fluctuations in heart rate after salt loading, whereas the systolic blood pressure (SBP, mmHg) and diastolic blood pressure (DBP, mmHg) increased and the corrected QT interval (QTc), corrected QT interval dispersion (QTdc) and Tp-Te values were significantly prolonged compared to that observed in the low-salt period (SBP, 118.6 ± 13.5 vs. 111.7 ± 11.3, p<0.01; DBP, 76.9 ± 8.6 vs. 71.7 ± 7.7, p<0.01; QTdc, 60.3 ± 19.4 vs. 55.6 ± 19.4, p<0.05; Tp-Te, 83.0 ± 10.1 vs. 79.8 ± 8.5, p<0.01). Surprisingly, all of these changes were reversed by potassium supplementation (SBP, 114.5 ± 12.3 vs.118.6 ± 13.5, p<0.01; DBP, 72.2 ± 7.9 vs.76.9 ± 8.6, p<0.01;QTd, 42.6 ± 15.1 vs. 47.4 ± 19.0, p<0.05; QTdc, 52.2 ± 18.0 vs. 60.3 ± 19.4, p<0.05; Tp-Te, 79.1 ± 8.5 vs. 83.0 ± 10.1, p<0.01). Conclusion Salt loading prolongs the QT interval, QTd and Tp-Te, while dietary potassium supplementation reverses these alterations. These findings suggest that potassium supplementation may improve variation in the healing time and prevent arrhythmia.

Sodium, Potassium, Blood Pressure, and Cardiovascular Disease in Humans

The scientific underpinning for recommended levels of dietary sodium and potassium intake is of great importance to healthcare providers and policy decision-makers. Recent clinical trials and meta-analyses confirm the capacity of dietary sodium reduction and potassium supplementation to reduce blood pressure with no harmful effects on blood lipid levels in customary clinical settings. Blood pressure is thought to be a good surrogate for cardiovascular disease events and the most important preventable risk factor for mortality and disability-adjusted life years. Cohort analyses and related pooling studies that have been used to explore the relationship between dietary Na and CVD were all based on secondary analyses of datasets that were not designed for this purpose. Most are of insufficient quality to provide dependable information. The limited information available from clinical trial experience and cohort studies of higher quality suggests a reduction in dietary Na decreases CVD morbidity and mortality. Modeling studies suggest that a small reduction in dietary sodium would result in a sizable general population health benefit. Some countries have experienced a progressive decline in average dietary sodium consumption. However, there is no evidence of a corresponding trend in the United States, and almost the entire population is failing to meet dietary sodium and potassium guideline recommendations.

Effect of salt intake and potassium supplementation on serum renalase levels in Chinese adults: a randomized trial.

Renalase, a recently discovered enzyme released by the kidneys, breaks down blood-borne catecholamines and may thus regulate blood pressure (BP). Animal studies have suggested that high levels of dietary salt might reduce blood and kidney renalase levels. We conducted a randomized trial to assess the effects of altered salt and potassium intake on serum renalase levels and the relationship between serum renalase levels and BP in humans.Forty-two subjects (28–65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day of NaCl), a high-salt diet for additional 7 days (18.0 g/day of NaCl), and a high-salt diet with potassium supplementation for final 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl).Serum renalase levels were significantly higher than baseline levels during the low-salt diet intervention period. Renalase levels decreased with the change from the low-salt to high-salt diet, whereas dietary potassium prevented the decrease in serum renalase induced by the high-salt diet. There was a significant inverse correlation between the serum renalase level and 24-h urinary sodium excretion. No significant correlation was found between the renalase level and BP among the different dietary interventions.The present study indicates that variations in dietary salt intake and potassium supplementation affect the serum renalase concentration in Chinese subjects.

Effect of dietary potassium supplementation on the calcium absorption capacity in the rumen and abomasum and fractional excretion of urinary minerals in sheep

The aim of this study was to determine the effect of potassium (K) supplementation on the calcium (Ca) absorption capacity from the rumen and abomasum of sheep. The Ca absorption capacity from the rumen and abomasum of sheep was measured using stable strontium (Sr) as a Ca-analogue tracer method. The sheep, cannulated at either the rumen or abomasum, were randomly allocated to one of two groups (control or K-supplemented) and fed in individual metabolism pens twice daily with a diet comprising oaten hay, lucerne chaff and barley fortified with or without potassium carbonate (K2CO3). The K content of the diet of the K-supplemented animals was 3.1% of dry matter compared with 1.4% for the control animals. The animals were fed their respective diets for a period of 2 weeks. The fractional absorption capacity (FC) of Ca was estimated before, during and after the treatment period. Supplementation with K decreased the FC of Ca in both the rumen and abomasum during treatment and increased the FC of Ca in the abomasum post-treatment. Supplementation with K also increased the fractional excretion of K in the urine, but decreased the fractional excretion of Ca and magnesium (Mg) (P &lt; 0.05), showing that K supplementation significantly affected Ca and Mg metabolism. Results suggest that renal conservation of Ca and Mg is an important mechanism controlling the Ca and Mg pool for vital functions of the body. In times of high demand for these minerals during lactation and pregnancy, high K in the diets may predispose sheep to hypomagnesaemia and hypocalcaemia, which in turn will have a negative impact on productivity and economic returns.

37 ROLE OF POTASSIUM ON RENAL PROTECTION IN DOCA/SALT MICE

Objectives: Recent animal and human studies have demonstrated that potassium depletion or hypokalemia in the presence of mineralocorticoid excess and high sodium state contributes to the pathogenesis of hypertension, stroke, arrhythmias, chronic heart and kidney diseases in association with tissue oxidative stress, inflammation, remodeling and fibrosis. We have recently reported that implantation of deoxycorticosterone-acetate (DOCA) with high salt diet in one-renin gene mice induced hypokalemia, coronary fibrosis, cardiac hypertrophy and dysfunction in absence of hypertension. The pathological changes in the DOCA treated mice can be reversed by reducing salt intake. Whether dietary potassium supplementation reverses DOCA/salt induced hypokalemia and cardiac and renal damages are unknown and studied? Method and Results: DOCA/salt mice progressively developed renal hypertrophy and fibrosis, albuminuria, and high serum creatinine associated with increased renal mRNA expression of transforming growth factor, tumor necrosis factor alpha, plasminogen activator inhibitor-1, fibronectin, collagen types I and III etc in absence of hypertension. Even late correcting hypokalemia by potassium supplementation to the DOCA/salt mice can partially reverse cardiac and renal hypertrophy, fibrosis, albuminuria, renal dysfunction in association with the reduction of the expression of the above genes in the kidney. In conclusion, potassium administration can prevent and reverse proteinuria, cardiac and renal hypertrophy and fibrosis and dysfunction induced by excess of DOCA and salt and hypokalemia independently of blood pressure reduction. Conclusion: These data provide strong evidence to suggest that potassium supplementation in the food might convey cost-effective cardiovascular protection to hypertensive patients.

Effect of potassium supplementation on renal tubular function, ambulatory blood pressure and pulse wave velocity in healthy humans

Background. Potassium is the main intracellular cation, which contributes to keeping the intracellular membrane potential slightly negative and elicits contraction of smooth, skeletal and cardiac muscle. A change in potassium intake modifies both cardiovascular and renal tubular function. The purpose of the trial was to investigate the effect of dietary potassium supplementation, 100 mmol daily in a randomized, placebo-controlled, crossover trial of healthy participants during two periods of 28 days duration. The participants (N = 21) received a diet that was standardized regarding energy requirement, and sodium and water intake. Methods. 24-hour ambulatory blood pressure (ABP) and applanation tonometry were used to assess blood pressure, pulse wave velocity (PWV), augmentation index (AIx) and central blood pressure (CBP). Immunoassays were used for measurements of plasma concentrations of vasoactive hormones: renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP), vasopressin (AVP), pro-brain natriuretic peptide (pro-BNP),endothelin (Endo), urinary excretions of aquaporin 2 (AQP2), cyclic AMP (cAMP), and the β-fraction of the epithelial sodium channel (ENaCß). Results. AQP2 excretion increased during potassium supplementation, and free water clearance fell. The changes in urinary potassium excretion and urinary AQP2 excretion were significantly and positively correlated. Aldo increased. GFR, u-ENaC- β, PRC, Ang II, ANP, BNP, Endo, blood pressure and AI were not significantly changed by potassium supplementation, whereas PWV increased slightly. Conclusions. Potassium supplementation changed renal tubular function and increased water absorption in the distal part of the nephron. In spite of an increase in aldosterone in plasma, blood pressure remained unchanged after potassium supplementation.ClinicalTrials.Gov Identifier: NCT00801034

Preventive dietary potassium supplementation in young salt-sensitive Dahl rats attenuates development of salt hypertension by decreasing sympathetic vasoconstriction

Increased potassium intake attenuates the development of salt-dependent hypertension, but the detailed mechanisms of blood pressure (BP) reduction are still unclear. The aims of our study were (i) to elucidate these mechanisms, (ii) to compare preventive potassium effects in immature and adult animals and (iii) to evaluate the therapeutic effects of dietary potassium supplementation in rats with established salt hypertension. Young (4-week-old) and adult (24-week-old) female salt-sensitive Dahl rats were fed a high-salt diet (5% NaCl) or a high-salt diet supplemented with 3% KCl for 5 weeks. The participation of vasoconstrictor (renin-angiotensin and sympathetic nervous systems) and vasodilator systems [prostanoids, Ca(2+) -activated K(+) channels, nitric oxide (NO)] was evaluated using a sequential blockade of these systems. Preventive potassium supplementation attenuated the development of severe salt hypertension in young rats, whereas it had no effects on BP in adult rats with moderate hypertension. Enhanced sympathetic vasoconstriction was responsible for salt hypertension in young rats and its attenuation for potassium-induced BP reduction. Conversely, neither salt hypertension nor its potassium-induced attenuation were associated with significant changes of the vasodilator systems studied. The relative deficiency of vasodilator action of NO and Ca(2+) -activated K(+) channels in salt hypertensive Dahl rats was not improved by potassium supplementation. The attenuation of enhanced sympathetic vasoconstriction is the principal mechanism of antihypertensive action exerted by preventive potassium supplementation in immature Dahl rats. Dietary potassium supplementation has no preventive effects on BP in adult salt-loaded animals or no therapeutic effects on established salt hypertension in young rats.

Genetic determinants of blood pressure reduction following potassium supplementation: and the candidates are…

Genetic determinants of blood pressure reduction following potassium supplementation: and the candidates are…