Body Sodium Research Articles

Magnetic resonance imaging determination of tissue sodium in patients with chronic kidney disease.

Excess sodium is a major modifiable contributor to hypertension and cardiovascular risk. Knowledge of sodium storage and metabolism has derived mainly from indirect measurements of dietary sodium intake and urinary sodium excretion, however both attempt to measure body sodium and fluid in a two-compartment model of intracellular and extracellular spaces. Our understanding of total body sodium has recently included a storage pool in tissues. In the last two decades, sodium-23 magnetic resonance imaging (23 Na MRI) has allowed dynamic quantification of tissue sodium in vivo. Tissue sodium is independently associated with cardiovascular dysfunction and inflammation. This review explores (i) The revolution of our understanding of sodium physiology, (ii) The development and potential clinical adoption of 23 Na MRI to provide improved measurement of total body sodium in CKD and (iii) How we can better understand mechanistic and clinical implications of tissue sodium in hypertension, cardiovascular disease and immune dysregulation, especially in the CKD population.

Abstract 23: Body Fluid And Sodium Loss Leads To Aldosterone Hypersecretion And Muscle Catabolism In Hepatocellular Carcinoma Rats.

Background: The number of cancer survivors coincides with cardiovascular diseases is increasing, therefore, we are promoting the concept of “Onco-Hypertension” to clarify the mechanism linking cancer and blood pressure. In this study, we evaluated body osmolyte and water imbalance in hepatocellular cancer (HCC) model rats. Methods: Wistar rats were administered diethylnitrosamine (DEN) (1.5 μg/day, p.o.), a carcinogenic drug, for 8 weeks to establish liver cancer. Three weeks after the completion of DEN administration, we investigated blood pressure, tissue osmolyte and water content, and its association with aldosterone secretion. Results: HCC rats significantly reduced blood pressure, skin sodium, potassium, and water content. In the carcass (muscle + bone), dry weight, sodium, potassium, and water content were dramatically reduced without changing bone mass in HCC rats, suggesting that HCC causes muscle wasting to supply osmolyte and water for the dehydrated organs. These osmolytes and water loss were significantly associated with increased urinary aldosterone excretion. Supplementation of 0.25% salt water to drink improved body sodium and water loss and muscle wasting in HCC rats, which were completely suppressed by treatment with spironolactone (75 mg/kg/day, p.o.), a mineralocorticoid receptor (MR) blocker. Conclusion: These findings suggest that HCC causes body osmolyte and water loss, which leads to aldosterone hypersecretion and muscle catabolism to compensate for dehydration. A relatively small amount of salt supplement ameliorates the HCC-induced dehydration and muscle wasting via aldosterone/MR-mediated sodium and water restoration.

Sex Differences in Diet Quality and Nutrient Intake in Adults Living With Chronic Kidney Disease

ObjectivesRecognition is growing that sex impacts outcomes in kidney disease. Women tend to have slower kidney function decline and better controlled risk factors pre-dialysis but the same mortality rates as men once dialysis starts. In the general population, women tend to have higher diet quality scores. Little is known about how sex differences impact diet quality and how this may explain known sex differences in this population. MethodsDiet History Questionnaire-3 (DHQ3) was administered to adults attending the Grey Nuns Hospital in Edmonton Alberta pre-dialysis (CKD; n = 46) or Hemodialysis (HD; n = 65) clinics. Healthy Eating Index (HEI) was used to assess diet quality. Nutrient intake was assessed per kg of body weight and adjusted for energy intake (i.e., per 1000kcal). Outcomes were assessed with subjects divided into sex category and clinic (CKD vs HD). Two tailed t-tests were used to test for sex differences in parametric variables. HEI scores were compared to age-matched general population values and sorted into below or above the comparator. Chi-square test were used to test for statistical significance in categorical variables. Results110 participants were included, 51 females and 60 males. There was no sex difference in mean HEI between females (61.2 ± 9.7) and males (59.9 ± 8.8; p = 0.464). 57% of females and 60% of males had HEI scores below mean age-matched HEI scores for the general population and no sex differences were observed. Pre-dialysis females had higher whole fruit composite scores vs pre-dialysis males (females 4.7 ± 0.7; males 3.8 ± 1.6, p = 0.015). Males consumed more total and mg/kg body weight protein, potassium, phosphorus and sodium than females (all p < 0.05); however, when intakes were adjusted for energy intake, there was no difference. ConclusionsIn this cohort of patients with CKD there were no observed differences in diet quality score between males and females. The majority of CKD patients had lower diet quality scores than the general population which might explain, to some extent, the few sex differences observed in this population. However, the higher whole fruit composite scores in pre-dialysis women may to some degree explain sex differences observed in pre-dialysis kidney disease. Further studies exploring dietary intake and sex differences in this population appear warranted. Funding SourcesNone.

013 Associations Between Rest-Activity Rhythms and Nocturnal Blood Pressure are Sex-Dependent in Apparently Healthy Emerging Adults

Abstract Introduction Misalignment between endogenous circadian rhythms and environmental signals – an emerging risk factor for cardiovascular disease (CVD) – can disrupt diurnal blood pressure (BP) rhythms, resulting in higher nocturnal BP and less-pronounced BP dipping (i.e., % decline in nighttime systolic BP [SBP] relative to daytime values). Daily patterns of rest and activity (‘rest-activity rhythms’ [RAR]) are a proxy for estimating circadian disruption in free-living settings and have been independently associated with elevated CVD risk. However, the relation between RAR and nocturnal BP is unclear. Thus, we aimed to quantify the associations between RAR and nocturnal BP characteristics in male and female emerging adults (18-25y). Methods Fifty healthy emerging adults (20±1y; 20M/30F) underwent 24-h ambulatory BP monitoring following 14 consecutive days of continuous wrist actigraphy. RAR variables of interdaily stability (IS; day-to-day consistency in RAR), intradaily variability (IV; within-day fragmentation of RAR), and relative amplitude (RA; difference between trough vs. peak activity) were computed. Bivariate correlations were used to quantify associations between RAR variables and nocturnal BP characteristics for all participants, and separately for males and females. Linear regression models of mean nocturnal SBP, nocturnal diastolic BP (DBP), and SBP dipping were also generated to test main and interactive effects of sex and RAR. Potential confounders (variables associated with outcomes at p&amp;lt;0.10) of daytime BP, race, body mass index, physical activity, sleep duration, alcohol, caffeine, and sodium intake were also included as indicated. Results Overall, IS and RA positively correlated with % SBP dipping (IS: r=0.33, p=0.02; RA: r=0.35, p=0.01). Among females only, correlations strengthened (IS: r=0.50, p&amp;lt;0.01; RA: r=0.52, p&amp;lt;0.01) and an inverse association between RA and mean nocturnal SBP emerged (r=-0.46, p=0.01). Conversely, among males, no significant associations were apparent. Multivariate regressions revealed a significant sex*RAR interaction, such that in females, every 1-standard deviation increase in IS and RA were associated with an average decrease in nocturnal SBP of 5.4 mmHg (95% CI: -10.0, -0.73) and 4.8 mmHg (95% CI: -9.2, -0.34), respectively. Conclusion Findings suggest that consistent and high-amplitude RAR associate with more favorable nocturnal BP characteristics, particularly in emerging female adults. Support (if any) Supported in part by NIH P20-GM113125.

A Four‐Week Urban Diet Impairs Vasodilation but Not Nutritional Physiology in Wild‐caught Mourning Doves (Zenaida macroura)

Birds living in urban areas routinely consume anthropogenic foods, but the physiological consequences of this consumption are poorly understood. To address this question, we investigated the effects of an urban diet (UD) in wild, urban-caught mourning doves in a controlled environment. Since anthropogenic foods often contain a high proportion of refined carbohydrate and fat, we predicted that UD consumption alters body mass as well as plasma and tissue metabolites and impairs vasodilation. To test this prediction, we compared the nutritional physiology and peripheral vasodilation of doves fed an UD (1:1 ratio of bird seeds and French fries; n=7) with those of doves receiving a control diet (CON: bird seed diet; n=6) for four weeks. At the end of the dietary manipulation period, birds were euthanized and we dissected cranial tibial arteries to measure ex vivovasodilation in response to acetylcholine treatment after phenylephrine-induced vasoconstriction. We also collected cardiac blood as well as liver, pectoralis and gastrocnemius muscle samples to measure nutritional metabolite concentrations. The vasodilation of tibial arteries was impaired in UD compared to CON-fed birds (p=0.004), suggesting the potential for UD consumption to cause cardiovascular pathologies. Neither body mass, plasma osmolality, glucose, sodium, insulin, triglyceride, uric acid, liver glycogen and triglycerides, nor muscle glycogen differed between groups. The results suggest that short term consumption of a diet comprised of 50% anthropogenic foods is not associated with major metabolic perturbations in urban mourning doves.

Cardiovascular Risk Factors in Young Adolescents: Results from the National Health and Nutrition Examination Survey 1988–2016

Lifestyle behaviors relevant to cardiovascular health are learned during childhood and continued into adulthood. Children and adolescents who participate in unhealthy behaviors have a higher lifetime risk of cardiovascular disease in adulthood. Public health institutions publish behavior and clinical recommendations designed for adolescents to reduce their lifetime cardiovascular risk. We assessed the prevalence and trends of cardiovascular-relevant behaviors and clinical tests among early adolescents using a nationally representative database. In 2020, we compared the prevalence of cardiovascular risk factors among 1408 adolescents surveyed from 1988 to 1994 with that of 1812 adolescents surveyed from 2011 to 2016 by obtaining and comparing measures on physical activity, diet, body mass index, smoking status, cholesterol levels, hemoglobin A1c, sodium intake, and blood pressure. The prevalence of adherence to the current recommendations regarding physical activity, diet, and body weight declined over time. Conversely, the prevalence of adhering to recommendations to avoid smoking increased. Clinical indicators, including blood pressure control and normal measures of hemoglobin A1c and total serum cholesterol, showed mixed results, with more individuals showing signs of hyperglycemia, fewer showing signs of hypercholesterolemia, and the percentage of individuals with abnormal blood pressure remaining the same. The use of cardiometabolic medications also increased during the study period. Finally, the number of adolescents with all seven cardiovascular protective factors declined significantly during the study period, from 27.6% to 9.6%. Modern American teenagers aged 12 to 16 years have more cardiovascular risk factors relating mostly to diet, exercise, and obesity than those of a prior generation; however, smoking rates have also declined precipitously.

Detection of Fully Cleaved Gamma Subunit of the Epithelial Sodium Channel (γ‐ENaC) in Kidney Cortex of Healthy and Nephrotic Wild Type Mice

Background and Objective The epithelial sodium channel (ENaC) located in the distal region of the nephron regulates body sodium homeostasis. It exhibits proteolytic posttranslational processing which leads to the removal of inhibitory peptide tracts and subsequent alterations in channel gating. Maximum channel activation and open probability occur at the proteolytic removal of the inhibitory tracts by serine proteases. Nephrotic Syndrome is thought to involve ENaC activation by full proteolysis of the gamma subunit and the detection of the expression of fully cleaved γ-ENaC has been elusive in vivo. Methods Three-month-old wild-type 129S1/SvImJ mice of both sexes were used for the experiment. Experimental nephrotic syndrome was induced by the use of doxorubicin. The mice were euthanized on days 4 and 8 and their kidneys were collected. Western blot analysis for γ-ENaC was performed with 20 µg of kidney lysate per lane. Samples were deglycosylated using Peptide: N-glycosidase F (PNGaseF). Subsequently, 20 µg of sample was loaded on an 8% polyacrylamide gel for electrophoresis. After transfer to nitrocellulose membranes, the blocked blots were incubated with the primary antibody against the γ-ENaC subunit overnight at 4°C in a 1:1000 dilution. γ-ENaC subunit was detected with a fluorescent secondary antibody labelled with IRDye 800CW. For loading control, total protein was measured using Revert Total Protein Stain. Anti-γ-ENaC was raised in rabbits against the C-terminal amino acids 634–655 of γ-ENaC (SPC-405, Stressmaq). Results Western blot analysis from murine kidney cortex samples for γ-ENaC revealed a band at 74 kDa and below this a blurry signal which extended until 64 kDa. Deglycosylation of the same samples using PNGaseF led to characteristic shifts of the migration pattern of γ-ENaC subunit. The most significant change was obtained where the migration pattern changed with three separate bands arising at 74, 60 and 53 kDa. The molecular mass of the obtained bands approximated the expected mass calculated from the amino acid sequence suggesting that these bands at 74, 60 and 53 kDa represent full length, furin-cleaved and fully cleaved γ-ENaC, respectively. Kidneys from nephrotic mice displayed increased expression of fully cleaved γ-ENaC in samples collected at day 8 after induction of nephrotic syndrome. Treatment of nephrotic mice with the serine protease inhibitor aprotinin normalized the expression of fully cleaved γ-ENaC. Conclusion Deglycosylation leads to the detection of the expression of fully cleaved γ-ENaC from kidney tissues. Nephrotic syndrome leads to increased expression of fully cleaved γ-ENaC which might mediates sodium retention.

A Four-Week Urban Diet Impairs Vasodilation but Not Nutritional Physiology in Wild-Caught Mourning Doves (Zenaida macroura).

AbstractBirds living in urban areas routinely consume anthropogenic foods, but the physiological consequences of this consumption are poorly understood. To address this question, we investigated the effects of an urban diet (UD) in wild, urban-caught mourning doves in a controlled environment. Since anthropogenic foods often contain a high proportion of refined carbohydrate and fat, we predicted that UD consumption alters body mass as well as plasma and tissue metabolites and that it impairs vasodilation. To test this prediction, we compared body mass, various nutritional physiology parameters, and peripheral vasodilation of doves fed an UD (1∶1 ratio of bird seeds and french fries; [Formula: see text]) with those of doves receiving a control diet (CON, bird seed diet; [Formula: see text]) for 4 wk. At the end of the dietary manipulation period, birds were euthanized, and we dissected cranial tibial arteries to measure ex vivo vasodilation in response to acetylcholine treatment after phenylephrine-induced vasoconstriction. We also collected cardiac blood as well as liver, pectoralis, and gastrocnemius muscle samples to measure nutritional metabolite concentrations. Vasodilation of tibial arteries was impaired in UD- compared to CON-fed birds ([Formula: see text]), suggesting the potential for UD consumption to alter cardiovascular function. Body mass, plasma osmolality, glucose, sodium, insulin, triglyceride, uric acid, liver glycogen and triglycerides, and muscle glycogen did not differ between groups. The results suggest that short-term consumption of a diet composed of 50% anthropogenic foods is not associated with major metabolic perturbations in urban mourning doves.

A Novel SCNN1A Variation in a Patient with Autosomal-recessive Pseudohypoaldosteronism Type 1

Pseudohypoaldosteronism type 1 (PHA1) is an autosomal-recessive disorder characterized by defective regulation of body sodium (Na) levels. The abnormality results from mutations in the genes encoding subunits of the epithelial Na channel. Patients with PHA1 present in infancy as being in adrenal crisis. A 41-day-old female who presented with recurrent adrenal crisis did not adequately respond to hydrocortisone and required mineralocorticoid therapy. The patient’s demographic data and clinical features were recorded. Blood samples were collected and tested for endocrine and metabolic characteristics and for use in genetic studies. Bidirectional Sanger sequencing of SCNN1A was conducted. The entire coding region of 12 exons and 20 bp of flanking intron were sequenced. Genetic analyses revealed a new mutation - c.729_730delAG (p.Val245Glyfs*65) - in SCNN1A exon four. Adrenal crisis during the neonatal period highlights the importance of early screening for PHA1. Genetic testing could help to anticipate the prognosis, severity, onset of the disease, and the mode of inheritance, especially given its extensive phenotype.

Growth failure and metabolic acidosis due to total body sodium depletion in an infant with an ileostomy.

Sodium is an essential nutrient and inadequate sodium intake and/or excessive sodium losses can result in suboptimal growth. Infants with ileostomies are at significant risk of developing growth failure as a result of excessive sodium loss in their ileostomy effluent. Chronic sodium depletion can also limit the kidney's ability to excrete hydrogen and potassium ions, mimicking electrolyte abnormalities found in type 4 renal tubular acidosis. This report describes an infant with an ileostomy with severe growth failure, hyperkalaemia and metabolic acidosis-all of which promptly resolved with sodium supplementation.

Developing a multimodal biosensor for remote physiological monitoring

IntroductionSeveral UK military expeditions have successfully used physiological sensors to monitor participant’s physiological responses to challenging environmental conditions. This article describes the development and trial of a multimodal wearable biosensor...

Factors that Contribute to the QTc Interval Prolongation in DR-TB Patients on STR Regimen

Introduction: QTc interval prolongation is one of the adverse drug reaction of several drugs used in DR-TBpatients treated with STR regimen. Drug-induced QTc prolongation can predispose patient to develop lifethreatening arrhythmia, increasing hospital length of stay and mortality. This study aims to determine factorsthat contribute to QTc prolongation in DR-TB patients on STR regimen.Methods. This was an observational retrospective study using medical records of DR-TB patients whoreceived STR regimen from August 2017 to March 2019 in tertiary hospital DR Soetomo, Surabaya,Indonesia. QTc interval was calculated by Fredericia formula. The influence of risk factors (age, bodyweight (BW), Body Mass Index (BMI), gender, comorbid, potassium, sodium and QTc baseline) with QTcprolongation was analyzed using multiple regression. The relationship between Moxifloxacin dosage andQTc was analyzed using Chi-Square test.Results Out of the 113 DR-TB patients who received the STR therapy regimen, 98 patients were eligible forthis study. They consist of 62 (%) male; 36 (%) female. Thirty-five (35,7%) of them had Diabetes Mellitusas a comorbid disease. The mean age of the patients was 44±11 years, with the mean of BMI was 20.20±3.73. Potassium and Sodium levels at the baseline were 4.192 ± 0.58 and 138.05 ± 4.562 respectively. TheQTc baseline before receiving STR regimen was 431.9±30,617ms. Patients received a dose of moxifloxacin400 mg (5.1%) , 600 mg (59,2%), and 800 mg (35,7%) according to body weight. There were no correlationbetween age, BW, gender, comorbid, and sodium baseline with QTc. There were correlation betweenpotassium (p=0,001), BMI (p=0,006) and QTc baseline (p &lt;0,001) with QTc.Conclusion QTc baseline and potassium level are factors that contribute to the prolongation of the QTcinterval.

Effect of Vitamin E And Selenium Injection on Some Physiological Characteristics And Biochemical Parameters in Local Ram Lamb

The aim of present study was to investigate the response of vitamin E and selenium injection in local ram lambs on the hematological aspect, thyroid hormones, biochemical parameters, and growth rate. Twenty-four weaned (3-4 month old) ram lambs and averaged 20.827±0.5 kg in weight were used. The lambs were divided randomly into three groups (8 lambs each). 1st group was served as the control, the lambs were injected with 1.0 ml\head of physiological saline solution (0.9%), 2nd group (T1), lambs were injected intramuscularly with vitamin E 2.5 mg/kg of body weight and sodium selenite 25μg/kg of body weight and 3rd group (T2), the lambs were injected intramuscularly with vitamin E 5 mg/kg of body weight and sodium selenite 50μg/kg of body weight. The injection administered at weekly interval for 12 weeks. Results showed that T1 significantly increased packed cell volume (PCV %) and lymphocytes. The result of current study did not show a significant change between the test group in growth rate, ESR, thyroid hormones, biochemical parameter including (glucose, total protein, albumin, globulin, cholesterol, and triglyceride and aspartate aminotransferase).In conclusion, injection of vitamin E and selenium has positive effect on some physiological parameters in local ram lamb.

Bioelectrical Impedance Analysis Identifies Patients With Worse Cardiorespiratory Fitness In Heart Failure With Reduced Ejection Fraction And Type 2 Diabetes Mellitus

Background Cardiorespiratory fitness (CRF) is an important prognostic indicator of morbidity and mortality in patients with heart failure (HF), especially in those with comorbid type 2 diabetes mellitus (T2DM). Bioelectrical impedance analysis (BIA) is an objective and reproducible method to estimate the edema index (EI), a surrogate for extracellular volume status. Whether an increase in the EI estimated by BIA can identify patients with reduced CRF is unknown. We hypothesized that in patients with HF and reduced ejection fraction (HFrEF) and T2DM, an increased EI would inversely correlate with measures of CRF. Methods We measured peak oxygen consumption (VO2), a measure of CRF, during maximal cardiopulmonary exercise testing and the EI (percentage of extracellular water divided by total body water) with BIA in 72 patients. Subjects underwent venipuncture during the same visit to collect biomarkers. Data are reported as median and interquartile range (IQR). To determine the relationship between peak VO2 and EI, we used Spearman rank correlation and linear regression models with and without adjustments for age, sex, race, body mass index (BMI), serum creatinine, C-reactive protein (CRP), hemoglobin, NTproBNP, sodium, and comorbidities (hyperlipidemia, hypertension). Results The majority of the 72 patients were female (69%), black (47%), had age of 58 (52-62) years and median BMI of 33.9 (31.2-37.6) kg/m2. Peak VO2, EI and NTproBNP were 15.7 (12.8-18.4) mL•kg−1•min−1, 45.5 (43.8-47.9) % and 344 (111-698) pg/mL, respectively. Peak VO2 inversely correlated with EI, BMI, NTproBNP and hemoglobin at univariate analysis (R=-0.307, p Conclusion In patients with HFrEF and T2DM, edema index is an independent predictor of CRF, with a greater EI reflecting increased extracellular volume being associated with lower CRF. These findings propose that using BIA to measure the EI have potential implications from a diagnostic, prognostic and therapeutic standpoint that clearly need to be explored in future studies.

Investigating the mechanism of vanadium toxicity in freshwater organisms

Vanadium (V) could present a risk for aquatic organisms from the Alberta oil sands region, if present in high concentrations. An industry pilot project has used petroleum coke (PC) as a sorbent to remove organic toxicants from oil sands process-affected water (OSPW), but it also caused V to leach from PC into the OSPW, reaching concentrations of up to 7 mg V/L (a level known to be toxic to aquatic organisms). Vanadium is a transition metal with several oxidation states, which could potentially elicit its toxicity through either ion imbalance or oxidative stress. This study investigated the effect of V on Daphnia magna and Oncorhynchus mykiss. Daphinds and O. mykiss were exposed to concentrations of V up to their respective calculated median lethal concentration (LC50): 3 mg V/L for D. magna and 7 mg V/L for O. mykiss. For both organisms, the influence of V on sodium flux and whole body sodium was evaluated. Its effect on whole body calcium and the oxidative stress responses in O. mykiss at the gill and liver levels was also studied. Results suggested that 3.1 mg V/L for D. magna and 6.8 mg V/L for O. mykiss caused an overall increase in sodium influx in both the daphnids and rainbow trout. However, concentrations of V ranging between 0.2 and 4 mg V/L for D. magna and 1.8 and 6 mg V/L for O. mykiss reduced whole body sodium in both organisms and whole body calcium in O. mykiss. Concentrations above 3.6 mg V/L caused significant lipid peroxidation in the gills and liver of rainbow trout, while 1.9 mg V/L produced a substantial decrease in the fish gill GSH:GSSG ratio, but no change in the ratio between these thiols in the liver. Concentrations of 6.62 mg V/L sharply increased catalase activity in the liver but not in the gills. Neither liver nor gill superoxide dismutase was altered by V. Overall, results suggest that both ion imbalance and oxidative stress are part of the mechanism of toxicity of V in D. magna and O. mykiss and that further research is warranted to fully elucidate the mechanism(s) of V toxicity in aquatic organisms.

Fluid management in chronic kidney disease: what is too much, what is the distribution, and how to manage fluid overload in patients with chronic kidney disease?

Assessment of fluid status to reach normovolemia in patients with chronic kidney disease (CKD) continues to be a tough task. Besides clinical observation, technological methods have been introduced, yet, the best approach is still uncertain. The present review looks at fluid overload in CKD from three perspectives: the critical fluid threshold leading to adverse cardiovascular outcomes, fluid distribution and its clinical correlates, and direct effect of fluid overload on vascular function related to disturbance of the sodium-skin axis and endothelial glycocalyx dysfunction. To determine fluid status, both the absolute and relative fluid overload is used as parameter in clinical practice. In addition, the definition of fluid overload is ambivalent and its relation to symptom burden has not been studied well. Studies on the impact of distribution of fluid are scarce and the limited evidence suggests differences based on the cause of CKD. So far, no standardized technologies are available to adequately determine fluid distribution. After discovering the 'third compartment' of total body sodium in skin and muscle tissue and its potential direct effect on vascular function, other biomarkers such as VEGF-C are promising. We propose a multimodal clinical approach for volume management in CKD. Because there are currently no studies are available demonstrating that correction of fluid overload in CKD will lead to better outcome, these are strongly needed.

Abstract P239: Diet Modifies Cardiometabolic Effects Of DOCA-salt In C57BL/6J Mice

The deoxycorticosterone acetate (DOCA)-salt model of hypertension is widely used to investigate the neurohormonal regulation of blood pressure. We investigated the modulatory effect of three common “chow” diets upon cardiometabolic consequences of DOCA-salt treatment in mice. Male C57BL/6J mice (6 wks of age) were randomly assigned to 5L0D (LabDiet 67138, 4.0 g Na/kg), a Soy-free extruded diet (Envigo 2920, 1.5 g Na/kg), or an NIH-31 modified open formula diet (Teklad 7913, 3.1 g Na/kg) and provided with autoclaved deionized water for 3 weeks (n=16/diet). At 9 weeks of age (ie, before DOCA-salt), intake behaviors and energy flux were assessed using metabolic caging and bomb calorimetry. Before DOCA-salt, body mass, digestive efficiency, energy efficiency, total sodium intake, urine volumes, and apparent sodium &amp; potassium retentions (ie, ingested-urine loss) were significantly modified by diet (p&lt;0.05), but calories absorbed per day was not. Mice (n=8/diet) were then implanted with a DOCA pellet (50mg, sc) and provided 0.15 M NaCl as an additional drink option, or underwent sham surgery (n=8/diet). At 12 weeks of age (ie, after DOCA-salt), intake behaviors and energy flux were again assessed before tissue harvest. After DOCA-salt, body mass, energy efficiency, total sodium intake, urine volume, apparent sodium retention, and renal renin mRNA were significantly affected by a diet x DOCA-salt interaction (p&lt;0.05). In contrast, digestive efficiency and apparent potassium retention were modified by diet (p&lt;0.05), and calories absorbed per day, plasma sodium, and plasma potassium were affected by main effects of diet (p&lt;0.05) and DOCA-salt (p&lt;0.05), but these endpoints were not modified by a diet x DOCA-salt interaction. Combined with analyses of tissue masses, expression of various renal electrolyte transporters, blood chemistries, and urinalyses, these many endpoints highlight a multitude of cardiometabolic outcomes of the DOCA-salt model that are sensitive to environmental contexts such as diet. Ongoing work is investigating the modulatory effect of diet upon increases in total body sodium retention and blood pressure induced by DOCA-salt treatment, and roles for varied sodium vs protein contents of the diets in these effects.

Abstract P180: Effect Of Sunitinib Treatment On Skin Sodium Accumulation In Patients With Metastatic Renal Cancer: A Pilot Study

Angiogenesis is required for invasive tumor growth and metastasis which is controlled mainly by vascular endothelial growth factors (VEGF). Novel strategies for cancer treatment target VEGF signaling. These agents are featured by adverse events including hypertension. New concepts suggest that besides the kidneys, the skin also plays a role in body sodium homeostasis and blood pressure regulation by a VEGF-C–dependent buffering mechanism. Here, we tested the hypothesis that changes in blood pressure correspond to tissue sodium accumulation during sunitinib treatment of metastatic renal cell carcinoma patients (https://clinicaltrials.gov/identifier: NCT04368546; Charité ethical approval EA1/044/15).Male patients (n=4) took sunitinib according to the standard treatment protocol, 50 mg once daily, taken for 4 weeks followed by a 2-weeks off treatment period. Measurements were performed at baseline (before sunitinib treatment), and over a complete on-off-on period. Tissue sodium content was measured using non-invasive 23Na-MRI; skin sodium was measured in a group (n=5) of age-matched healthy subjects, as well. Blood pressure was measured according to AHA guidelines. Blood withdrawal followed after ca. 45 minutes of sitting to measure VEGF-A, VEGF-C, endothelin-1, renin and aldosterone levels.Elevated systolic blood pressure under sunitinib treatment decreased to the baseline level in the off-treatment phase (130.5 mmHg vs 117.5 mmHg, respectively, p&lt;0.05). Plasma endothelin-1 levels mirrored directly and VEGF-A levels inversely the blood pressure changes. Baseline skin sodium content was similar to the skin sodium level of healthy controls. Skin sodium content was elevated after the first on-treatment phase and stayed high in all the following measurements in comparison to control subjects. Patients had high baseline VEGF-C levels that decreased after the first treatment with sunitinib and stayed low independently of further treatment phase.In conclusion, sunitinib treatment suppresses VEGF-C levels permanently which is associated with sustained elevated skin sodium levels. Furthermore, we confirmed the association between plasma endothelin-1 levels and blood pressure changes during sunitinib treatment protocol.

Counterpoint: Investigators should not control for menstrual cycle phase when performing studies of vascular control that include women.

Observed sex differences in the epidemiology of cardiovascular disease incidence and the efficacy of clinical intervention strategies, coupled with recent mandates from the National Institutes of Health (NIH), and its international counterparts to consider sex as a biological variable in all preclinical and clinical work (15), have led to increased enrollment of women in human physiology studies of vascular function with the goal of improving external validity and clinical applicability of the findings. However, standard practice in these studies is to test women during the early follicular phase (~days 1-5) of the menstrual cycle, during which estrogen and progesterone concentrations are lowest, and either exclude or limit testing of women who use hormonal contraceptives to the placebo phase. This approach seeks to control for, or limit, differences in circulating hormone concentrations between men and women and is based on the dogmatic theory that cyclic changes in estrogen and progesterone concentrations lead to greater variability in study outcomes and uninterpretable datasets. Contrary to this common approach, we propose that limiting testing of women to this single phase 1) decreases external validity of the findings, 2) obfuscates potential physiological differences contributable to differences in sex hormone concentrations between men and women, and 3) is, in many instances, contradicted by literature that demonstrates limited or no variability in vascular measurements across the menstrual cycle.

Planeación y cumplimiento de metas del tratamiento de la hipertensión arterial sistémica en el anciano

Introducción: El incumplimiento de las metas de tratamiento hipertensivo, favorece la aparición temprana de alteraciones cognitivas y afecta la funcionalidad del anciano. Una de las funciones afectadas es la planeación, componente de las funciones ejecutivas que permite al individuo programar tareas y tomar decisiones. Objetivo: Determinar la relación entre la planeación y las metas de cumplimiento del tratamiento hipertensivo en ancianos. Metodología: Diseño descriptivo-correlacional que incluyó 52 personas mayores de 60 años, hombres y mujeres, con diagnóstico de hipertensión arterial sistémica, reclutados en grupos de ayuda mutua en el Estado de Jalisco. Se aplicó la Torre de Londres, se midió presión arterial, índice de masa corporal, colesterol total, consumo de sodio y tabaco. Se realizaron varias mediciones para establecer relaciones entre ellas. Resultados: Predominaron las mujeres (80.8%), la media de edad fue 70.2 años (DE=6.8) y de evolución de hipertensión arterial sistémica fue de 11.0 años (DE=7.3). Se identificaron correlaciones débiles (p=&lt;.05) entre presión arterial y total de movimientos correctos, presión arterial y tiempo total de resolución; e índice de masa corporal y violación total de reglas. Conclusión: Los ancianos con mayores dificultades en la planeación fueron los que presentaron mayor incumplimiento del tratamiento hipertensivo y de forma específica con el índice de masa corporal, por ello, los profesionales de enfermería deben vincular esfuerzos para fortalecer las estrategias que apoyen a los ancianos en la modificación del estilo de vida.