Hyperkalemia Research Articles

Association between serum potassium and Parkinson's disease in the US (NHANES 2005-2020).

Evaluating the correlation between serum potassium and Parkinson's disease (PD) in US adults. A cross-sectional study was conducted on 20,495 adults aged 40 years or older using NHANES data from 2005 to 2020. The study utilized one-way logistic regression and multifactorial logistic regression to examine the correlation between serum potassium levels and PD. Additionally, a smoothed curve fitting approach was employed to assess the concentration-response relationship between serum potassium and PD. Stratified analyses were carried out to investigate potential interactions between serum potassium levels and PD with variables such as age, sex, race, marital status, education, BMI, smoking and medical conditions like coronary, stroke, diabetes, hypertension, and hypercholesterolemia. In this study, a total of 20,495 participants, comprising 403 PD and 20,092 non-PD individuals, were included. After adjusted for covariates, multivariable logistic regression revealed that high serum potassium level was an independent risk factor for PD (OR:1.86, 95% CI:1.45 ~ 2.39, p < 0.01).The linear association between serum potassium and PD was described using fitted smoothing curves. Age, sex, race, education, marital, BMI, coronary, stroke, diabetes, hypertension and hypercholesterolemia were not significantly correlated with this positive connection, according to subgroup analysis and interaction testing (P for interaction >0.05). Serum potassium levels are elevated in patients with Parkinson's disease compared to non-PD patients. Additional prospective studies are required to explore the significance of serum potassium levels in individuals with Parkinson's disease.

Association of Preoperative Serum Potassium With Postoperative Seizures in Patients Undergoing Elective Craniotomy

BACKGROUND AND OBJECTIVES: Patients who undergo craniotomy are at risk of developing seizures during the postoperative period. Preoperative serum potassium as an important potential risk factor has not been investigated yet. METHODS: We conducted a retrospective cohort study involving adults undergoing elective craniotomy at West China Hospital, from January 2011 and March 2021. The main outcome of this study was postoperative seizures in patients undergoing elective craniotomy during hospitalization. We performed univariable and multivariable logistic regression to investigate the association of preoperative serum potassium with postoperative seizures. RESULTS: A total of 15 041 patients were collected after filtering by excluded criteria. The incidence of postoperative seizures was 4.87%. We identified a linear relationship between preoperative serum potassium and postoperative seizures (P for nonlinearity =.87). Compared with patients with serum potassium 3.5 to 4.5 mmol/L, the odds of postoperative seizures increased in patients with serum potassium ≥4.5 mmol/L (the adjusted odds ratios 1.46, 95% CI 1.10-1.93), and the odds of postoperative seizures decreased in patients with serum potassium ≤3.5 mmol/L (the adjusted odds ratios 0.73, 95% CI 0.53-1.01). CONCLUSION: We found that high preoperative serum potassium level was associated with the high risk of postoperative seizures in patients undergoing craniotomy. We demonstrated that preoperative serum potassium level was the independent risk factor of postoperative seizures.

Influence of Organic Nutrients on Growth and Yield of Summer Greengram (Vigna radiata)

Greengram ( Vigna radiata L. ), commonly called as mungbean is an important pulse crop grown mainly in Zaid and Kharif season in India. Organic farming is one of the sustainable farming practices that can overcome the harmful effects of chemical farming and provides quality production. A field experiment was conducted during Zaid, 2023 to study the “Effects of organic nutrients on growth and yield of summer Greengram (Vigna radiata L.)” at SHUATS Model Organic Farm, Department of Agronomy, SHUATS, Prayagraj (U.P). The experiment was laid out in a randomized block design with nine treatments replicated thrice. The treatment consisted of 3 different solid manures i.e. Farm Yard Manure, Vermicompost, Goat manure and 3 different liquid manures i.e. Fish Amino Acid, Panchagavya and Seaweed (Kappaphycus alvarezii) sap. The experimental field soil was sandy loam in texture, moderately basic in reaction (pH 7.8), available medium Organic Carbon (0.662 %) low in available nitrogen (249.5 kg/ha), and very high accessible phosphorus (38.7 kg/ha) and available potassium (240.8 kg/ha). The result showed that significantly higher growth parameters viz., plant height (42.09 cm), number of nodules (22.22/plant), dry weight (19.35g/plant) and yield attributes such as effective pod/plant (11.05), seed/pod (9.68), test weight (38.41 g), seed yield (1643.54 kg/ha) and stover yield (3023.55 kg/ha) were observed with application 5 t/ha FYM and foliar spray of 7.5 % K sap (T9). Highest net return (Rs. 100383.30/ha) and benefit cost ratio (1.84) was also recorded in the same treatment. This concludes that application of 5 t/ha FYM along with foliar spray of 7.5 % K sap at 15 and 30 DAS performed better in terms of yield and economic returns.

Effect of Foxtail Millet Cultivars on Yield and Yield Attributes under Different Sowing Windows

The investigation conducted at the Agronomy Farm, College of Agriculture, Pune, during the Kharif season of 2022 focused on the "Effect of foxtail millet cultivars on yield and yield attributes under different sowing windows." The study employed a split-plot design with sixteen treatments and three replications, involving four sowing dates (26 MW, 28 MW, 30 MW, and 32 MW) and four foxtail millet varieties (SiA 3156, SiA 3085, Suryanandi, and Renadu). The soil, a clay loam with slightly alkaline pH, low nitrogen, medium phosphorus, and high potassium levels, received RDF 60:30:30 N: P2O5: K2O kg ha-1 at sowing. The investigation monitored various growth parameters, including plant height, number of tillers, number of functional leaves, and dry matter accumulation, at different growth stages. The study revealed that early sowing at 26 MW significantly influenced plant height, number of tillers, and dry matter production, favoring greater vegetative growth. The Renadu variety consistently exhibited superior performance in plant height, tiller count, and dry matter accumulation compared to other varieties. Days to 50% flowering and maturity were significantly affected by both sowing dates and varieties, with early-sown crops taking more days to reach these stages. Grain yield, straw yield, and harvest index were influenced by sowing dates and varieties, with the combination of the Renadu variety and 26 MW sowing exhibiting the highest grain yield and straw yield. Renadu also displayed a superior harvest index, emphasizing its suitability for optimal growth and yield. The study recommends sowing foxtail millet on 26 MW or 28 MW, particularly with the Renadu variety, for achieving maximum growth and yield during the Kharif season. The findings highlight the significance of considering both sowing windows and foxtail millet varieties to optimize production in the given agro-climatic conditions of Pune, Maharashtra.

The impact of temperature on vascular function in connection with vascular laser treatment

Pulsed dye lasers are used effectively in the treatment of psoriasis with long remission time and limited side effects. It is, however, not completely understood which biological processes underlie its favorable outcome. Pulsed dye laser treatment at 585-595 nm targets hemoglobin in the blood, inducing local hyperthermia in surrounding blood vessels and adjacent tissues. While the impact of destructive temperatures on blood vessels has been well studied, the effects of lower temperatures on the function of several cell types within the blood vessel wall and its periphery are not known. The aim of our study is to assess the functionality of isolated blood vessels after exposure to moderate hyperthermia (45 to 60°C) by evaluating the function of endothelial cells, smooth muscle cells, and vascular nerves. We measured blood vessel functionality of rat mesenteric arteries (n=19) by measuring vascular contraction and relaxation before and after heating vessels in a wire myograph. To this end, we elicited vascular contraction by addition of either high potassium solution or the thromboxane analogue U46619 to stimulate smooth muscle cells, and electrical field stimulation (EFS) to stimulate nerves. For measurement of endothelium-dependent relaxation, we used methacholine. Each vessel was exposed to one temperature in the range of 45-60°C for 30 seconds and a relative change in functional response after hyperthermia was determined by comparison with the response per stimulus before heating. Non-linear regression was used to fit our dataset to obtain the temperature needed to reduce blood vessel function by 50% (Half maximal effective temperature, ET50). Our findings demonstrate a substantial decrease in relative functional response for all three cell types following exposure to 55°C-60°C. There was no significant difference between the ET50 values of the different cell types, which was between 55.9°C and 56.9°C (P>0.05). Our data show that blood vessel functionality decreases significantly when exposed to temperatures between 55°C-60°C for 30 seconds. The results show functionality of endothelial cells, smooth muscle cells, and vascular nerves is similarly impaired. These results help to understand the biological effects of hyperthermia and may aid in tailoring laser and light strategies for selective photothermolysis that contribute to disease modification of psoriasis after pulsed dye laser treatment.

Consumption of ultra-processed foods and relationship with sodium and potassium excretion: a cross-sectional study

Introduction: Higher consumption of ultra-processed foods (UPF) had been associated with higher risk of non-communicable diseases (NCD) and NCD-promoting nutrient profile such as high sodium content and low potassium content. The objective of the study was to evaluate the level of food processing according to the NOVA classification and its relationship with sodium and potassium intake estimated by 24-hour urinary excretion. Methods: This is a cross-sectional study. Data collection included 107 workers from a public university (51.4% female; mean age 47 years) participating in an iMC Salt clinical trial). A 24-hour urinary collection was used to estimate sodium and potassium intake, validated by the creatinine coefficient. The corresponding 24-hour dietary recall was used to assess food intake and foods were categorized using the NOVA classification according to the degree and purpose of processing, into four groups. Nutri-score was also used to categorize UPF and provide more information about the nutritional quality of products. Results: The largest energy contribution came from the group of unprocessed or minimally processed foods (51.6%), followed by UPF (24%), processed foods (21.8%) and processed culinary ingredients (2.6%). Individuals with the lowest caloric contribution of the consumption of UPF had higher average values of potassium (K) intake (1438 vs 1136 mg/1000kcal; p=0.007), as individuals with the highest weight contribution of the consumption of unprocessed or minimally processed foods (1434 vs 1109 mg/1000kcal; p=0.010). For sodium (Na) intake no significant results were found between individuals with the lowest and the highest consumption of each NOVA group. Conclusions: Higher consumption of fresh or minimally processed foods and lower UPF intake were associated with higher K intake values. On the other hand, higher UPF intake was not associated with higher Na intake values. Funding: This work was supported by Fundação para a Ciência e Tecnologia by Grant POCI-01-0145-FEDER-029269) and by the European Regional Development Fund (ERDF) through NORTE 2020 (Northern Regional Operational Program 2014/2020) - NORTE-01-0145-FEDER-072687.

Balancing sodium and potassium: Implication of mTORC2-mediated ENaC activation in DCT2 and early CNT for potassium balance in high dietary potassium

Background: The activity of the epithelial sodium ion channel, ENaC, and ENaC-dependent potassium (K+) secretion through ROMK are influenced by both aldosterone-dependent and independent mechanisms in response to dietary potassium (K+). While ENaC activity in the late connecting tubule (CNT) and cortical collecting duct (CCD) depends on aldosterone, it is aldosterone-independent in the late distal convoluted tubule (DCT2) and early CNT (eCNT). Aldosterone-stimulated ENaC activity relies on SGK1, transcriptionally upregulated by aldosterone and subsequently phosphorylated and activated by mTOR complex-2 (mTORC2). Recent evidence suggests that high potassium can rapidly activate mTORC2/SGK1 signaling to stimulate ENaC. In this study, we explore mTORC2’s role in K+ secretion and aldosterone-independent ENaC regulation. Methods: Rictor, a core component of mTORC2, was selectively knocked out (KO'd) in DCT2, CNT and CD by utilizing Calbindin as Cre-driver (CRKO mice) or late CNT and CD, by employing AQP2 as the Cre-driver (ARKO mice). Both wild-type (WT) and KO mice were subjected to a high potassium (HK) diet for short-term (4 hours) or medium-term (48 hours) periods, enabling the monitoring of both the early response and prolonged adaptation to the HK diet. Parameters assessed include urinary and blood electrolyte levels, renal transporter expression, activity and localization, and mTORC2 target phosphorylation. Results: On a normal K+ diet, both KO mice maintained Na+ and K+ balance but CRKO mice had elevated aldosterone levels. After short-term (4-hour) HK intake, CRKO mice had disrupted Na+ and K+ balance, reduced K+ excretion and hyperkalemia. In contrast, ARKO mice maintained Na+ and K+ balance with elevated aldosterone. On a prolonged HK diet (48 hours), CRKO mice had severe hyperkalemia, reduced GFR and significantly elevated aldosterone level. Immunofluorescence studies indicated markedly reduced apical localization of active ENaC in DCT2/eCNT of CRKO mice. Conversely, ENaC apical localization in the late CNT and CCD was mostly unaffected. Phosphorylation of mTORC2 targets involved in ENaC regulation, such as SGK1, and SGK1’s target, Nedd4-2, was also reduced in CRKO mice. ARKO mice maintained ion balance with normal K+ levels but significantly increased aldosterone levels and maintained ENaC apical localization in the late CNT and CCD. Conclusions: The data suggest that high aldosterone can compensate mTORC2 deficiency and maintain ENaC activity in the late CNT and CCD. However, mTORC2 activity is crucial for maintaining ENaC activity in the late DCT and early CNT (aldosterone-independent) and preserving potassium balance during high dietary potassium intake. National Institutes of Health (R01- DK56695), James Hilton Manning and Emma Austin Manning Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dietary potassium effects on renal calcium transport at single nucleus resolution

Calcium homeostasis is maintained by the coordination of the intestines, bones, and kidneys. Dietary calcium is absorbed in the intestines, enters the bloodstream, and eventually finds its place in the bone reservoir or undergoes filtration by the glomerulus before being reabsorbed throughout the nephron. The late distal convoluted tubule (DCT2) and connecting tubule (CNT) determine the final rate of urinary calcium excretion, since no calcium reabsorption takes place beyond the connecting tubule (CNT). When excess calcium is excreted in the urine, also known as hypercalciuria, it contributes to the development of osteoporosis and the formation of kidney stones. High dietary potassium intake is strongly associated with a lower risk of kidney stone formation. Yet, the precise mechanism by which potassium intake modulates calcium excretion is not clear. To examine the transcriptional changes linking high dietary potassium intake and calcium transport, we applied single-nucleus RNA-sequencing (snRNA-Seq) in enriched distal nephron cells. To achieve the enrichment, we crossed a Calbindin 1 (Calb1)-driven Cre mouse line with the INTACT (for Isolation of Nuclei TAgged in Specific Cell Types) reporter line, which allows the GFP reporter to be expressed at the nuclear envelope of all calbindin 1-expressing cells. As the Calb1-Cre is constitutively expressed, all cells that have calbindin 1 expression at any time point during development will express the reporter. We examined the GFP expression by immunofluorescence, and found that it is expressed along the entire distal nephron from the distal convoluted tubule (DCT), CNT, to the collecting duct (CD). Male Calb1-Cre-INTACT mice were provided either a normal (NK, 1.05%) or a high (HK, 2%) potassium diet for 4 days and kidneys were snap-frozen for targeted snRNA-Seq using 10X Chromium (n=3 mice per group, targeting 10,000 nuclei per mouse). Our snRNA-seq dataset showed 6 major clusters, including DCT (DCT1 and DCT2), CNT (3 subclusters), CD principal cells (3 subclusters), ɑ-intercalated cells (2 subclusters), β-intercalated cells (2 subclusters), and proliferating cells. We curated a calcium score from the expression of known calciotropic genes ( Slc8a1, Vdr, Trpv5, Calb1, S100g, Ryr2, Trpv6) and used it as an index of calcium handling capacity. The calcium score is the highest in DCT2 and CNT along the distal nephron. In all CNT subclusters of the HK-treated animals, the calcium score is higher compared to the NK-treated animals, suggesting more calcium transport in CNT. Given that HK stimulates aldosterone and causes CNT hypertrophy, we compared the results with mice subjected to low dietary potassium (LK) treatment and metolazone (thiazide) treatment. The aim was to delineate the effects of dietary potassium and aldosterone A comprehensive summary of plasma potassium levels, urinary calcium excretion, aldosterone levels, calcium scores, and CNT morphology has been presented in the table below. Notably, the comparative analysis reveals a significant correlation between aldosterone levels and CNT size, both of which exhibit an inverse relationship with urinary calcium excretion: [Formula: see text] Our results suggest that DCT2 and CNT are the major sites for calcium transport. Yet, CNT exhibit more heightened adaptability in response to physiological or pharmacological perturbations at both transcriptional and morphological levels. Calcium homeostasis coincides with the regulation of aldosterone levels and CNT remodeling. DK51496 and DK133220 to DHE; K01DK121737 and AHA 20CDA35320169 to JWN. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Risk factors for diabetic retinopathy, diabetic macular edema, and sight-threatening diabetic retinopathy

ObjectiveTo identify the risk factors for the development of diabetic retinopathy (DR), diabetic macular edema (DME), and sight-threatening DR (STDR) based on a city-wide diabetes screening program. Research design and methodsDiabetic patients were prospectively recruited between June 2016 and December 2022. All patients underwent dilated fundus photography centered on the disc and macula or macular spectral domain optical coherence tomography (SD-OCT) scan. Complete medical history was documented. Systematic examination, blood analysis, and urinalysis were performed. Multivariate logistic regression analysis adjusting for age and sex was conducted. ResultsOut of 7274 diabetic patients, 6840 had gradable images, among which 3054 (42.0%) were graded as DR, 1153 (15.9%) as DME, and 1500 (20.6%) as STDR. The factors associated with DR, DME, and STDR included younger age (odds ratio [OR]: 0.96, 0.97, and 0.96 respectively), lower BMI (OR: 0.97, 0.95, and 0.95 respectively), longer duration of diabetes (OR: 1.07, 1.03, and 1.05 respectively) and positive of urinary albumin (OR: 2.22, 2.56, and 2.88 respectively). Other associated factors included elevated blood urea nitrogen (OR: 1.22, 1.28, and 1.27 respectively), higher LDL-cholesterol, lower blood hemoglobin (OR: 0.98, 0.98, and 0.98), insulin intake, presence of diabetic foot pathologies and diabetic peripheral neuropathy. We also identified novel risk factors, including high serum potassium (OR: 1.37, 1.46, and 1.55 respectively), high-serum sodium (OR: 1.02, 1.02, and 1.04 respectively). Better family income was a protective factor for DR, DME, and STDR. Alcohol consumption once a week was also identified as a protective factor for DR. ConclusionsSimilar risk factors for DR, DME, and STDR were found in this study. Our data also indicates high serum sodium, high serum potassium, low blood hemoglobin, and level of family income as novel associated factors for DR, DME, and STDR, which can help with DR monitoring and management.

The Effect of Dietary Sodium and Potassium Consumption on Intestinal Permeability and its Relation to Blood Pressure, and Endothelial Function: A Pilot Study

High sodium (HS) diets can reduce endothelial function (EF) and increase blood pressure (BP) while high potassium (HK) diets are shown to counter this effect. Furthermore, HS diets have also been shown to lead to gut dysbiosis, which is related to increased intestinal permeability (IP). However, the effect of HS diets on IP and whether the addition of HK can attenuate potential HS-induced changes to IP is unknown. Hypotheses: We hypothesized IP would increase on a HS diet and be mitigated by HK and that a higher IP would be related to elevations in BP and lower EF. Methods: Eleven healthy participants (5W/6M, age 32±8 yrs, BMI 23±1, BP 105±6/66±7 mmHg) consumed three 10-day diets of differing sodium and potassium content in randomized order: low sodium (LS)/low potassium (LK) (50mmol/65mmol), HS/LK (300mmol/65mmol), and HS/HK (300mmol/120mmol). On day 9 of each intervention, they collected their urine and wore an ambulatory BP monitor for 24-hr. On day 10, brachial artery flow-mediated dilation (FMD) was measured. Blood was collected and lipopolysaccharide-binding protein (LBP), a biomarker of IP and bacterial translocation, was measured by ELISA. Mixed design ANOVAs assessed sex differences in LBP, FMD, and BPs between diets. Simple linear regressions assessed relations between variables. Results: Twenty-four-hr urinary sodium excretion was higher on both HS diets compared to LS/LK diet (both p&lt;0.01) and 24-hr urinary potassium excretion was higher on HS/HK compared to LS/LK and HS/LK diets (both p&lt;0.01). LBP was different between diets (p&lt;0.01), and there was a significant diet*sex interaction (p=0.02) where men had increased LBP compared to women on the HS/LK and HS/HK diets (both p&lt;0.01). FMD was not different between diets (p=0.13) although men had a lower FMD compared to women after each diet (sex: p&lt;0.01). Twenty-four-hr mean arterial pressure (MAP) was different between diets (p=0.047) as men demonstrated higher 24-hr MAP on the HS/LK diet compared to LS/LK diet (p=0.03) and lower MAP on the HS/HK diet compared to HS/LK diet (p=0.01). LBP was inversely related to FMD (r=-0.82, p&lt;.01) and positively related to MAP (r=0.72, p&lt;.01), 24-hr systolic BP (r=0.66, p=0.03), and 24-hr diastolic BP (r=0.66, p=0.03) on the HS/LK diet for all participants, but not the LS/LK or HS/HK diets. Conclusions: These pilot data suggest that HS diets may increase IP in men, and, in the context of a HS/LK diet, greater IP is associated with lower FMD and higher BP in all participants. NIH R01 HL145055. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Humanized Diets Define Optimal Pressure Lowering Response to Dietary Potassium in Mice

High potassium (K) diets are known to lower blood pressure (BP) in rodents and humans but can also raise BP when consumed in extreme. Interestingly, this response also appears to be influenced by dietary sodium (Na) such that when Na intake is high, high K lowers BP, whereas when sodium intake is lower, high K increases BP (Little et al, Hypertension, 2023). We recently reported (Little et al, JCI Insight, 2023) that the K-mediated BP lowering response, driven by the inactivation of the thiazide-sensitive sodium chloride cotransporter (NCC), is offset by an increase in ENaC (epithelial sodium channel) when an extremely high K diet is chronically consumed. Here, we define the optimal dietary K level needed to inactivate NCC without activating ENaC in the high Na setting and show this K level approximates the recommended level for humans by the DASH (Dietary Approaches to Stop Hypertension) trials. Mice were fed diets containing 6 different K contents, all with high Na (1.7%), so the effects of the control diet (1% K, 1.7% Na) could be compared to traditional extremes (0.1% and 5% K) and others (0.35%, 0.7%, 1.7%) that mimic typical variation in human diets (30-120 mEq/d) when mouse consumption is normalized for caloric intake relative to body mass. Metabolic cage and renal clearance studies were used to assess electrolyte and aldosterone (aldo) excretion as well as NCC- (hydrochlorothiazide (HCTZ) sensitive) and ENaC- (benzamil sensitive) dependent sodium handling. Blood potassium (PK) was measured using iSTAT. BP was measured hourly for 10 days using DSI telemetry probes in male mice (C57Bl6J). The BP response to the diuretics was also measured. PK levels changed significantly with each diet relative to the control diet from 3.2mM to 4.8mM. Systolic blood pressure (SBP; 12-hour active period average) also changed significantly with the different K diets. Extreme high or low K diets (0.1% and 5%) increased SBP by 7mmHg, 0.35% and 0.7% K diets increased SBP by 6 and 3mmHg, while the 1.7% K diet lowered SBP by 4mmHg relative to control (1% K, 132 mmHg). Thus, the relationship between SBP and PK is ‘U-shaped’. Diuretic studies revealed that HCTZ reduces SBP in the 0.1%, 0.35%, 0.7% K groups but had minimal effect in the 1.7% and 5% K groups. Conversely, inhibiting ENaC activity with benzamil normalized SBP in the 5% K group but had a minimal effect in the 1.7% group and no BP effect in the other groups. The BP-lowering effect of each diuretic correlated with increased natriuresis suggesting dietary K influences blood pressure by affecting distal nephron sodium transport. Lastly, urinary aldo levels increased with increasing dietary K, but compared to the control group, aldo levels were significantly lower in the 0.1%, 0.35%, and 0.7% groups, significantly higher in the 5% group, and not different in the 1.7% group. As previously reported, our results demonstrate that extremes in dietary intake can elevate blood pressure by stimulating distal nephron sodium transport proteins with low K inducing NCC activation and high K stimulating ENaC with elevated aldosterone. An optimal dietary K level (1.7%) that maximally reduces BP in mice was identified, suppressing NCC activity while limiting aldosterone production and ENaC activity. Remarkably, this diet mimics the human DASH diet in K content and further supports its effcacy as a blood pressure-lowering modality. DE (DK054231, DK51496); PW (DK054231, DK093501, DK110375): Leducq Foundation U54 DK137331-01. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Mitochondria control IP3-evoked Ca2+ release triggered by voltage-dependent Ca2+ entry in intact resistance arteries

The contractility of vascular smooth muscle cells (VSMCs) is a major contributor of vascular tone and blood pressure. In VSMCs, intracellular Ca2+ level determines the contractile activity that generates the force to contract arteries. A major source of Ca2+ is via influx through voltage dependent Ca2+ channels (VDCCs). While mitochondria are now recognised as key regulators of intracellular Ca2+ homeostasis in several cell types, their role in modulating Ca2+ signalling mediated by VDCC in VSMCs is unresolved. Given the potential physiological significance, and unclarified interaction between mitochondria and VDCCs in VSMCs, we hypothesize that mitochondria directly regulate Ca2+ signalling mediated by VDCCs. The interplay between mitochondria and VDCCs was investigated by imaging and analysing intracellular Ca2+ signals in smooth muscle cells in intact arteries from rat mesentery. Depolarization of the plasma membrane potential, by high potassium (20 mM) physiological saline solution, triggered Ca2+ influx through VDCCs and a sustained increase in intracellular Ca2+ on which repetitive Ca2+ oscillations occurred. All Ca2+ signals were abolished by removal of external Ca2+ and by dihydropyridine inhibitors of VDCCs. Significantly, the repetitive Ca2+ oscillations, but not the sustained Ca2+ signals, were blocked by the IP3 receptor inhibitor 2-APB and SERCA inhibitor cyclopiazonic acid. Neither the repetitive Ca2+ oscillations or the sustained Ca2+ signals were altered by the ryanodine receptor inhibitors ryanodine and dantrolene. These results suggest that Ca2+ influx via VDCC triggers Ca2+-induced Ca2+ release at IP3 receptors in intact mesenteric arteries. Depolarization of the mitochondrial membrane potential (ψm), with the uncoupler CCCP or complex I inhibitor rotenone, but not ATP deprivation with the ATP synthesis blocker oligomycin, inhibited VDCC evoked IP3 mediated Ca2+ oscillations but not the sustained Ca2+ signals. Furthermore, in intact arteries, depolarization of ψm directly suppressed inositol triphosphate receptors (IP3Rs) mediated Ca2+ release from the internal Ca2+ store evoked by photolysis of caged IP3. These results suggest that mitochondria regulate Ca2+ release via IP3R triggered by Ca2+ entry via VDCC. In return, Ca2+ entry via VDCCs did not alter ψm, but upregulated ROS production. Together, these results suggest that mitochondria regulate Ca2+-induced Ca2+ release at IP3 receptors triggered by Ca2+ influx via VDCCs but do not directly regulate VDCC activity. British Heart Foundation (RG/F/20/110007; PG/20/9/34859). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Investigation of slagging-fouling tendency for high-sulfur coal and solid recovered fuel (SRF)

SRF can be utilized as co-firing fuel in power plants in order to provide more green energy and decrease the waste landfill. However, the characteristics of SRF with high potassium and chlorine need to be investigated first to avoid ash problem aspects in the future. This study aims to obtain initial prediction of slagging, fouling, abrasion, and corrosion for SRF and high-sulfur coal blend using empirical indices. This study used five slagging parameters, four fouling parameters, one abrasion parameter, and two corrosion parameters. The result shows that SRF contains high ash content, chlorine, Fe2O3, CaO, and K2O, that affects ash deposit formation like slagging, fouling, abrasion, and corrosion. Therefore, composition of 0-15 wt% SRF is more suitable than other compositions.

Effects of potassium supplementation and deficiency on the progression of salt-sensitive hypertension

While the physiological effects of sodium on blood pressure are well established, many of the effects of potassium remain unclear. Prior work found that increased potassium intake decreases blood pressure and risk of cardiovascular disease, improves vasodilation, has reno-protective effects, and can stimulate natriuresis. In this study, we examined how different sodium/potassium ratios affect the development of salt-sensitive hypertension, specifically examining changes in the kidney and the renin angiotensin aldosterone system (RAAS). We hypothesized that blood pressure would directly correlate to the Na+/K+ ratio and that there would be compensatory changes in RAAS and in expression of renal potassium channels, particularly inwardly rectifying potassium (Kir) channels. At 9 weeks of age, male and female Dahl SS rats were placed on a high salt (4% NaCl) diet for 5 weeks with normal potassium (NK, 0.36% K+), high potassium (HK, 1.41% K+), or potassium depleted (DK, &lt;0.0001% K+) diet. After 5 weeks of dietary intervention, DK animals were hypokalemic, and HK animals had significantly increased plasma potassium. Potassium supplementation attenuated the development of salt-sensitive hypertension in male rats fed the HK diet compared to NK; the DK group did not develop hypertension. Potassium supplementation did not attenuate blood pressure in female rats, who also had a higher mortality rate on the DK diet. Heart rates were unchanged in both male and female HK groups but were significantly lower in the DK groups of both sexes. After 5 weeks of diet, the total body weights of DK rats were significantly lower. The 2 kidney/total body weight ratios were not different between the HK and NK groups, but the kidneys of the DK group were significantly larger, likely due to their smaller body weights. Medullary protein casts in DK rats of both sexes were decreased but no renoprotective effects were observed in the HK group. Western blot analysis of renal potassium channels demonstrated no changes in the expression of ROMK, significantly increased Kir5.1 in DK males and females, and a significant increase in Kir4.1 and the alpha-subunit of the Na+/K+-ATPase in DK males. We analyzed RAAS metabolites from plasma samples collected at the endpoint: Ang I (1-10), Ang IV (3-8), and Ang (1-5) were significantly decreased in DK males and females, Ang II (1-8) and Ang III (2-8) were significantly reduced in DK males, and aldosterone was significantly increased in HK males and females. These results provide a comprehensive assessment of how various potassium diets affect the development of salt-sensitive hypertension in both males and females, which will provide a solid foundation for future mechanistic studies. R01DK129227, I01 BX004024, R35HL135749. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

ACUTE EFFECTS OF SODIUM CHLORIDE OR ITS SUBSTITUTE POTASSIUM CHLORIDE ON VASCULAR FUNCTION IN HEALTHY VOLUNTEERS

Objective: High blood pressure, one of the most important risk factors for cardiovascular mortality, leads to vascular dysfunction and subsequently to arteriosclerosis, stroke, kidney and heart failure. High salt intake and low potassium intake are associated with high blood pressure and an increased risk of cardiovascular disease and mortality. Partial replacement of sodium with potassium led to a lower risk of cardiovascular events and death in a long-term follow-up study. However, the exact mechanism remains unclear. Our aim was to investigate the acute effects of sodium or potassium intake on vascular health to unravel the underlying mechanisms leading to vascular adaptations. Design and method: Six male and nine female healthy individuals (mean age 31 years) were randomized to either 9g of sodium chloride (high salt group), 6g of sodium chloride (regular salt group) or 6 g of sodium chloride plus 3g of potassium chloride group (substitution group). Individuals received a salty soup with the corresponding sodium or potassium load. Blood analyses, blood pressure, body composition and macro- as well as microvascular measurements were performed before as well as four (t4) and 24 hours (t24) after soup intake. To investigate macrovascular health, carotid-to-femoral pulse wave velocity was analyzed. Microvascular health was measured by investigating retinal vessel diameters. Results: The high (139±2mmol/l vs. 143±2mmol/l p=0,003) and regular salt group (140±2mmol/l vs. 141±0,6 mmol/l p=0,029) showed both higher serum sodium concentrations at t4 compared to baseline. These higher values were normalized at t24. The serum sodium concentration of the substitution group showed no statistically significant difference between timepoints. The substitution group showed improved microvascular health, quantified by higher arteriolar-to-venular diameter ratio from baseline to t4 (0,86±0,09 vs. 0,89±0,08 p=0,005). These improvements were regressive at t24 (0,88±0,09). No statistically significant changes were found on pulse wave velocity. The high and regular salt group showed no statistically significant differences at any timepoint on micro- or macrovascular health parameters. Conclusions: Replacement of sodium by potassium seems to improve microvascular function directly after potassium intake. These results might explain the long-term beneficial effects of potassium on cardiovascular outcomes.

Sodium Zirconium Cyclosilicate in HFrEF and Hyperkalemia: REALIZE-K Design and Baseline Characteristics

BackgroundMineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns. ObjectivesThe purpose of this study was to assess whether sodium zirconium cyclosilicate (SZC), a nonabsorbed crystal that traps and rapidly lowers potassium, enables MRA use in patients with HFrEF and prevalent hyperkalemia (or at high risk). MethodsREALIZE-K is a prospective, double-blind, placebo-controlled trial in patients with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal therapy (except MRA), and prevalent hyperkalemia (or at high risk). During the open-label run-in, all participants underwent protocol-mandated spironolactone titration (target: 50 mg daily); those with prevalent (cohort 1) or incident (cohort 2) hyperkalemia during titration started SZC. Participants achieving normokalemia while on spironolactone ≥25 mg daily were randomized to continuing SZC or matching placebo for 6 months. The primary composite endpoint was proportion of participants with optimal response (normokalemia, on spironolactone ≥25 mg daily, no rescue for hyperkalemia [months 1-6]). ResultsOf 365 patients (run-in), 202 were randomized. Baseline characteristics included mean age 70 years, prevalent comorbidities (78% estimated glomerular filtration rate <60 mL/min/1.73 m2, 38% atrial fibrillation/flutter), high N-terminal pro B-type natriuretic peptide (median 1,136 pg/mL), and high HFrEF therapy use (64% sacubitril/valsartan, 96% beta-blocker, 42% sodium glucose co-transporter 2 inhibitor). At randomization, 78% were receiving spironolactone 50 mg daily. ConclusionsREALIZE-K is the first trial to evaluate whether SZC can enable rapid and safe MRA optimization and long-term continuation in patients with HFrEF and prevalent/high risk of hyperkalemia. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients with Symptomatic HFrEF Receiving Spironolactone [REALIZE-K]; NCT04676646)

Potassium Supplementation Offsets the Effects of a High Sodium Diet on Endothelial Function but Not Blood Pressure Reactivity in Healthy, Normotensive Adults

High sodium diets are linked to endothelial dysfunction and increased blood pressure reactivity (BPR) to physiological stimuli, which are both notable cardiovascular disease (CVD) risk factors. High potassium diets are shown to lower blood pressure (BP) and improve endothelial function; however, previous interventions often increased potassium intake using food, making it diffcult to attribute these effects to potassium alone. The interactive effects of sodium and potassium on pre-clinical CVD risk factors remains unclear. The objective of this study was to determine if potassium can independently counteract the effects of a high sodium diet on endothelial function and BPR in healthy, normotensive adults. We hypothesized that endothelial function and BPR would be impaired with a high sodium diet compared to a low sodium diet but would improve with the addition of potassium supplements. Nineteen participants (13W/6M, age 26±4 y, BP 108±11/71±9 mmHg, BMI 25.1±2.7 kg/m2) completed three 10-day controlled diets in random order: a moderate potassium/low sodium (MK/LS; 55 mmol K/50 mmol Na) diet, a moderate potassium/high sodium (MK/HS; 55 mmol K/300 mmol Na) diet, and a high potassium/high sodium (HK/HS; 120 mmol K/300 mmol Na) diet. Potassium intake was increased using potassium chloride supplements. Dietary compliance was confirmed by urinalysis. On day 10, endothelial function was assessed by brachial artery flow-mediated dilation (FMD), and BPR was assessed by measuring ΔMAP in response to an isometric handgrip exercise (IHG) with post-exercise ischemia (PEI) and the cold pressor test (CPT). Differences across diets were assessed by repeated-measures ANOVA. Twenty-four-hour ambulatory mean arterial pressure (MAP), which was measured on day 9, was not different across diets (MK/LS: 81±5 mmHg; MK/HS: 79±4 mmHg; HK/HS: 80±6 mmHg; p=0.15), indicating our participants were salt-resistant. FMD was significantly lower on the MK/HS diet compared to the MK/LS diet (MK/HS: 5.8±2.8% vs. MK/LS: 8.2±3.7%; p=0.004) and was rescued with the addition of potassium supplements (HK/HS: 8.9±3.2; p=0.009 compared to MK/HS). FMD on MK/LS and HK/HS diets were similar (p&gt;0.05). There were no differences across diets in ΔMAP in response to the IHG (p=0.73), the PEI (p=0.67), or the CPT (p=0.94). Our findings suggest that, while sodium and potassium may not affect BPR, potassium supplementation effectively counteracts sodium-induced endothelial dysfunction in healthy, normotensive, salt-resistant adults. AHA/VIVA 23POST1009835; NHLBI R01 HL145055. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Effect Of Drinking Sirsak Leaves (Annona Muricata Linn) On Reducing Blood Pressure In Menopause Women With Hipertension

Hypertension or high blood pressure is a disorder of the blood vessels that results in the supply of oxygen and nutrients carried by the blood being obstructed to the body's tissues. Hypertension is often referred to as the Silent Killer, because it is a dark killer disease without being accompanied by symptoms first. Soursop leaf (Annona Muricata Linn) is a traditional medicine used as a therapy for hypertension, the content of soursop leaves which is thought to reduce blood pressure is potassium ions. High potassium levels can increase sodium excretion, as a result it can reduce blood volume &amp; blood pressure. Menopause in women is associated with the depletion of ovarian follicles accompanied by physical and psychological changes. One of the comorbidities often experienced by menopausal women is hypertension. The purpose of this study was to determine the effect of soursop leaf decoction on lowering blood pressure in menopausal women with hypertension. This type of research is a quasi experiment (quasi experimen). This study uses a one group pretest-postest design, which is a treatment design using only the experimental group without a comparison or control group. Based on the results of the study seen from 15 respondents obtained with the Wilcoxon test results, it can be seen that the resulting p-value is 0.000. This means that p &lt; (a = 0.05), this shows that there are changes in blood pressure in wa.

Fluorine-doped porous carbon coating on Sn/SnOx as anode materials for high-performance potassium ion batteries

Potassium-ion batteries (PIBs) are considered alternatives to lithium-ion batteries because of their comparatively cheaper manufacturing costs and lower potential (2.936 V compared to standard hydrogen electrodes). However, their large ionic radii and unstable structures hindered their satisfactory electrochemical performance. In this study, F–Sn/SnOx@C, a novel porous layered composite material, was prepared using NaCl as a template for in situ etching to obtain a promising negative electrode material for PIBs. The significant specific surface area of the composite material and the uniform embedding of tin nanoparticles within the layered porous carbon shell, contributed to its excellent potassium intercalation/deintercalation performance. Fluorine doping enhanced electron transfer, prevented nanoparticle aggregation, and improved electrolyte penetration and potassium ion migration. The PIBs prepared from this electrode showed high potassium storage capacity, outstanding cycle stability (retaining 263 mAh g−1 after 200 cycles at 100 mA g−1), and remarkable rate capability (505.6, 288.4, 193.5, 134.1, and 83.3 mAh g−1 at 0.1, 0.2, 0.3, 0.5, and 1.0 A g−1, respectively). These results provide a straightforward solution for improving the electrochemical performance of PIBs.

Tumor lysis syndrome following letrozole for locally advanced breast cancer: a case report

BackgroundLetrozole, an aromatase inhibitor, is used to treat breast cancer in postmenopausal women. Tumor lysis syndrome (TLS) is a complication that can trigger multiple organ failure caused by the release of intracellular nucleic acids, phosphate, and potassium into the blood due to rapid tumor cell disintegration induced by drug therapy. TLS is uncommon in solid tumors and occurs primarily in patients receiving chemotherapy. Herein, we report a rare occurrence of TLS that developed in a patient with locally advanced breast cancer following treatment with letrozole.Case presentationAn 80-year-old woman with increased bleeding from a fist-sized left-sided breast mass presented to our hospital. Histological examination led to a diagnosis of invasive ductal carcinoma of the luminal type. The patient refused chemotherapy and was administered hormonal therapy with letrozole. Seven days after letrozole initiation, she complained of anorexia and diarrhea. Blood test results revealed elevated blood urea nitrogen (BUN) and creatinine (Cr) levels, and she was admitted to our hospital for intravenous infusions. On the second day after admission, marked elevations of LDH, BUN, Cr, potassium, calcium, and uric acid levels were observed. Furthermore, metabolic acidosis and prolonged coagulation capacity were observed. We suspected TLS and discontinued letrozole, and the patient was treated with hydration, febuxostat, and maintenance hemodialysis. On the third day after admission, her respiratory status worsened because of acute respiratory distress syndrome associated with hypercytokinemia, and she was intubated. On the fourth day after admission, her general condition did not improve, and she died.ConclusionsAlthough TLS typically occurs after chemotherapy initiation, the findings from the present case confirm that this syndrome can also occur after hormonal therapy initiation and should be treated with caution.