Browsing by Subject "Sodium"

Now showing 1 - 10 of 28
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    Adiposity has unique influence on the renin-aldosterone axis and blood pressure in black children
    (Elsevier, 2013-11) Yu, Zhangsheng; Eckert, George; Liu, Hai; Pratt, J. Howard; Tu, Wanzhu; Medicine, School of Medicine
    OBJECTIVE: To comparatively examine the effects of adiposity on the levels of plasma renin activity (PRA), plasma aldosterone concentration (PAC), and aldosterone-renin ratio (ARR) in young black and white children. STUDY DESIGN: We prospectively assessed 248 black and 345 white children and adolescents. A novel analytical technique was used to assess the concurrent influences of age and body mass index (BMI) on PRA, PAC, and ARR. The estimated effects were depicted by colored contour plots. RESULTS: In contrast to whites, blacks had lower PRA (2.76 vs 3.36 ng/mL/h; P < .001) and lower PAC (9.01 vs 14.59 ng/dL; P < .001). In blacks, BMI was negatively associated with PRA (P = .001), consistent with an association with a more expanded plasma volume; there was no association with PAC. In whites, BMI was positively associated with PAC (P = .005); we did not detect a BMI-PRA association. The effects of BMI on ARR were directionally similar in the two race groups but more pronounced in blacks. Mean systolic blood pressure was greater in blacks with lower PRA (P < .01), higher PAC (P = .015), and higher ARR (P = .49). CONCLUSIONS: An increase in adiposity was associated with a suppressed PRA in blacks and an increase in PAC in whites. The unique relationship between adiposity and renin-aldosterone axis in blacks suggests the possible existence of a population-specific mechanism characterized by volume expansion, which could in turn enhance the influences of adiposity on blood pressure in black children and adolescents.
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    Aldosterone-induced proteins in primary cultures of rabbit renal cortical collecting system
    (1996-10) Bindels, Rend J.M.; Engbersen, A.M.T.; Hartog, A.; Blazer-Yost, Bonnie
    Primary cultures of immunodissected cells from rabbit kidney connecting tubule and cortical collecting duct were used to study aldosterone's action on transcellular Na+ flux. Incubation with 10(-7) M aldosterone stimulated transcellular Na+ transport which was detected as an increase in benzamil-sensitive short-circuit current. The stimulatory response was consistently noted after 2 h of incubation and stabilized after 6 h. 2D-PAGE was used to identify proteins which were induced concurrently with the increase in transcellular Na+ flux after an aldosterone incubation of 15 h. Three aldosterone-induced proteins (AIPs; M(r) = 100, 70-77 and 46-50 kDa) were found in the membrane and microsomal fractions. Two of these appeared to have more than one isoform. A single heterogeneous AIP (M(r) = 77 kDa) was detected in the soluble fraction.
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    Application of 23Na MRI to Monitor Chemotherapeutic Response in RIF-1 Tumors
    (Elsevier, 2005-07) Babsky, Andriy M.; Hekmatyar, Shahryar K.; Zhang, Hong; Radiology and Imaging Sciences, School of Medicine
    Effects of an alkylating anticancer drug, cyclophosphamide (Cp), on 23Na signal intensity (23Na SI) and water apparent diffusion coefficient (ADC) were examined in subcutaneously - implanted radiation-induced fibrosarcoma (RIF-1) tumors by in vivo23Na and 1H magnetic resonance imaging (MRI). MRI experiments were performed on untreated control (n = 5) and Cp-treated (n = 6) C3H mice, once before Cp injection (300 mg/kg) then daily for 3 days after treatment. Tumor volumes were significantly lower in treated animals 2 and 3 days posttreatment. At the same time points, MRI experiments showed an increase in both 23Na SI and water ADC in treated tumors, whereas control tumors did not show any significant changes. The correlation between 23Na SI and water ADC changes was dramatically increased in the Cp-treated group, suggesting that the observed increases in 23Na SI and water ADC were caused by the same mechanism. Histologic sections showed decreased cell density in the regions of increased 23Na and water ADC SI. Destructive chemical analysis showed that Cp treatment increased the relative extracellular space and tumor [Na+]. We conclude that the changes in water ADC and 23Na SI were largely due to an increase in extracellular space. 23Na MRI and 1H water ADC measurements may provide valuable noninvasive techniques for monitoring chemotherapeutic responses.
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    Assessment and Management of Hypertension among Patients on Peritoneal Dialysis
    (American Society of Nephrology., 2019-02-07) Vaios, Vasilios; Georgianos, Panagiotis I.; Liakopoulos, Vassilios; Agarwal, Rajiv; Medicine, School of Medicine
    Approximately 7%-10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population.
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    Characterization of hormone-stimulated Na+ transport in a high-resistance clone of the MDCK cell line
    (1996-08) Blazer-Yost, Bonnie; Record, Rae D.; Oberleithner, Hans
    The Madin-Darby canine kidney (MDCK) cell line forms an epithelial monolayer which expresses many of the morphological and functional properties of the renal collecting duct. The C7 subclone of the parent line forms an epithelium which expresses many of the characteristics of principal cells. The MDCK-C7 subclone forms a high-resistance epithelium that is capable of vectorial ion transport. We have found that this epithelium responds to aldosterone, antidiuretic hormone (ADH) and insulin like growth factor 1 (IGF1) with increases in amiloride-sensitive Na+ transport. The responses to aldosterone and ADH follow time-courses that are consistent with the action of these hormones in vivo. This is the first demonstration of IGF1-induced Na+ reabsorption in a mammalian model system. Interestingly, a maximal response to any one of these natriferic factors does not inhibit a subsequent response to another hormone. These studies indicate that the C7 subclone retains many of the natriferic responses of the native principal cells and is an ideal model for studying hormonal modulation of Na+ transport.
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    Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Serum Electrolyte Levels in Patients with Type 2 Diabetes: A Pairwise and Network Meta-Analysis of Randomized Controlled Trials
    (Wolters Kluwer, 2022-01-19) Zhang, Jingjing; Huan, Yonghong; Leibensperger, Mark; Seo, Bojung; Song, Yiqing; Epidemiology, School of Public Health
    Background: Previous studies have reported that sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2is) affect levels of serum electrolytes, especially magnesium. This study aimed to integrate direct and indirect trial evidence to maximize statistical power to clarify their overall and comparative effects in patients with type 2 diabetes (T2D). Methods: We systematically searched PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov up to January 2021 to identify eligible randomized controlled trials (RCTs) of SGLT2is that reported mean changes in serum electrolytes, including magnesium, sodium, potassium, phosphate, and calcium. We performed both random-effects pairwise and network meta-analyses to calculate the weighted mean difference (WMD) and 95% confidence intervals (CI). Results: In total, we included 25 RCTs involving 28,269 patients with T2D and 6 SGLT2is. Compared with placebo, SGLT2is were significantly associated with elevations in serum magnesium by 0.07 mmol/L (95% CI, 0.06 to 0.08 mmol/L) and serum phosphate by 0.03 mmol/L (95% CI, 0.02 to 0.04 mmol/L). Our network meta-analysis showed no evidence of significantly superior efficacy of any specific SGLT2 inhibitor over the others, although dapagliflozin was associated with a larger increment in serum magnesium (WMD=0.16 mmol/L) compared with other SGLT2is. Similarly, no statistically detectable differences among the effects of SGLT2is on serum levels of other electrolytes were detected. Conclusions: SGLT2is significantly increased serum magnesium and phosphate levels, consistent with a class effect of SGLT2 inhibition. However, further investigations of long-term efficacy and safety in patients with T2D with different clinical phenotypes are needed.
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    Consideration of Kinase Inhibitors for the Treatment of Hydrocephalus
    (MDPI, 2023-04-03) Blazer-Yost, Bonnie L.; Biology, School of Science
    Hydrocephalus is a devastating condition characterized by excess cerebrospinal fluid (CSF) in the brain. Currently, the only effective treatment is surgical intervention, usually involving shunt placement, a procedure prone to malfunction, blockage, and infection that requires additional, often repetitive, surgeries. There are no long-term pharmaceutical treatments for hydrocephalus. To initiate an intelligent drug design, it is necessary to understand the biochemical changes underlying the pathology of this chronic condition. One potential commonality in the various forms of hydrocephalus is an imbalance in fluid-electrolyte homeostasis. The choroid plexus, a complex tissue found in the brain ventricles, is one of the most secretory tissues in the body, producing approximately 500 mL of CSF per day in an adult human. In this manuscript, two key transport proteins of the choroid plexus epithelial cells, transient receptor potential vanilloid 4 and sodium, potassium, 2 chloride co-transporter 1, will be considered. Both appear to play key roles in CSF production, and their inhibition or genetic manipulation has been shown to affect CSF volume. As with most transporters, these proteins are regulated by kinases. Therefore, specific kinase inhibitors are also potential targets for the development of pharmaceuticals to treat hydrocephalus.
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    Dietary Electrolytes and their Influences on Plasma Aldosterone Concentration
    (2019-06) Ye, Xiaohan; Tu, Wanzhu; Katz, Barry P.; Bakoyannis, Giorgos; Yiannoutsos, Constantin T.
    Excessive sodium retention is thought to be the main culprit for hypertension. The modern American diet provides an excess of sodium and not sufficient amount of sodium. In this research, we examined the relations among urinary sodium and potassium excretion, and plasma levels of aldosterone, a mineralocorticoid hormone that has been linked to incidence hypertension, in a cohort of healthy children and young adults. We found that higher plasma aldosterone level was associated with lower sodium excretion in the urine, in blacks and whites, suggesting that aldosterone plays a critical role in retaining the sodium from dietary sources. The study highlights the importance of dietary sodium restriction.
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    Differential effects of brefeldin A on hormonally regulated Na + transport in a model renal epithelial cell line
    (1994) Blazer-Yost, Bonnie; Coupaye-Gerard, Brigitte; Kim, Hyun Jin; Singh, Anup
    Na+ transport in renal epithelia is regulated by a wide variety of endogenous and exogenous cellular factors. Although most natriferic agents have an action on the amiloride-sensitive Na+ channel, the biochemical pathways which precede activation of the channel remain incompletely defined. One approach to dissecting such intricate pathways is to perturb a specific cellular process and determine its importance in the postulated mechanism. The current studies examine the effect of brefeldin A (BFA), an inhibitor of the central vacuolar system, on basal as well as aldosterone-, insulin-, and forskolin-stimulated Na+ transport. In the A6 cell line, BFA had a time-dependent effect on basal transport. Aldosterone-induced Na+ transport was sensitive to BFA while insulin's action was only partially blocked and forskolin-stimulated Na+ transport was relatively resistant to the action of the inhibitor. These studies highlight differences as well as points of convergence in the natriferic pathways.
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