Keyu Ren

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

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

Genetic Variants in Renalase and Blood Pressure Responses to Dietary Salt and Potassium Interventions: A Family-Based Association Study

Background/Aims: Renalase (gene name RNLS), a recently discovered enzyme with monoamine oxidase activity, is implicated in the degradation of catecholamines. Recent studies indicate that common variations in the gene with RNLS are associated with hypertension. The aim of this study was to examine the association between genetic variants in RNLS and blood pressure (BP) responses to strict dietary interventions of salt and potassium intake. Methods: A total of 334 subjects from 124 families were selected and sequentially maintained on a low-salt diet for 7 days (3.0 g/day, NaCl), then a high-salt diet for 7 days (18.0 g/day, NaCl), high-salt diet with potassium supplementation for another 7 days (4.5 g/day, KCl). Results: SNPs rs919115 and rs792205 of the RNLS gene were significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) responses to high-salt intervention. In addition, rs12356177 was significantly associated with systolic BP (SBP) and DBP responses to low-salt diet, and SBP, DBP or MAP during the high-salt intervention. Unfortunately, no associations for the 7 RNLS SNPs with BP response to high-salt diet with potassium supplementation reached nominal statistical significance. Conclusions: This family-based study indicates that genetic variants in the RNLS gene are significantly associated with BP responses to dietary salt intake.

Effects of a High Salt Intake and Potassium Supplementation on QT Interval Dispersion in Normotensive Healthy Subjects

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

High-salt intake suppressed microRNA-133a expression in Dahl SS rat myocardium.

Salt-sensitive individuals show earlier and more serious cardiac damage than nonsalt-sensitive ones. Some studies have suggested that microRNA-133a could reduce cardiac hypertrophy and myocardial fibrosis. The current study aims to investigate the different functions of high-salt intake on salt-sensitive (SS) rats and Sprague-Dawley (SD) rats and the involvement of microRNA-133a in these roles. After high-salt intervention, the left ventricular mass (LVW) and left ventricular mass index (LVMI) of the salt-sensitive high salt (SHS) group were obviously higher than those of the salt-sensitive low salt (SLS) group. However, the difference between the Sprague-Dawley high salt (DHS) group and the Sprague-Dawley low salt (DLS) group was not significant. Compared with SLS group, collagen I and connective tissue growth factor (CTGF) in the heart of SHS group were significantly higher, whereas no statistical difference was observed between the DHS group and the DLS group. Compared with low-salt diet, microRNA-133a in the heart of both strains were significantly decreased, but that in the SHS group decreased more significantly. These results suggest that high salt intervention could down-regulate the expression of myocardial microRNA-133a, which may be one of the mechanisms involved in myocardial fibrosis in salt-sensitive hypertension.

Common Variants in Serum/Glucocorticoid Regulated Kinase 1 (SGK1) and Blood Pressure Responses to Dietary Sodium or Potassium Interventions: A family-Based Association Study

Background/Aims: Serum/Glucocorticoid Regulated Kinase 1 (SGK1) plays a significant role in regulating renal Na+ reabsorption, K+ secretion, and blood pressure (BP). This study aimed to assess the association of common genetic variants in the SGK1 gene with BP responses to controlled dietary sodium or potassium interventions. Methods: A total of 334 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially maintained a seven-day low-sodium diet (3g/day of NaCl or 51.3mmol/day of sodium), a seven-day high-sodium diet (18g/day of NaCl or 307.8 mmol/day of sodium) and a seven-day high-sodium plus potassium supplementation intervention (4.5g/day of KCl or 60mmol/day of potassium). Six single-nucleotide polymorphisms (SNPs) in the SGK1 gene were selected. Results: After adjustment for multiple testing, SNP rs9376026 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-sodium intervention (P = 0.018 and 0.022, respectively). However, the associations between selected SNPs in the SGK1 gene and BP responses to high-sodium or high-sodium plus potassium-supplementation intervention did not reach statistical significance. In addition, SNP rs9389154 and two other SNPs (rs1763509 and rs9376026) were associated respectively with systolic BP (SBP) and DBP at baseline (P = 0.040, 0.032, and 0.031, respectively). SNP rs3813344 was significantly associated with SBP, DBP, and MAP (P = 0.049, 0.015 and 0.018, respectively). Conclusion: Our study indicates that the genetic polymorphism in the SGK1 gene is significantly associated with BP responses to dietary sodium intervention.

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

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

Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13BN rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure.Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13BN rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure.

Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

Overweight/obesity is a chronic disease that carries an increased risk of hypertension, diabetes mellitus, and premature death. Several epidemiological studies have demonstrated a clear relationship between salt intake and obesity, but the pathophysiologic mechanisms remain unknown. We hypothesized that ghrelin, which regulates appetite, food intake, and fat deposition, becomes elevated when one consumes a high-salt diet, contributing to the progression of obesity. We, therefore, investigated fasting ghrelin concentrations during a high-salt diet. Thirty-eight non-obese and normotensive subjects (aged 25 to 50 years) were selected from a rural community in Northern China. They were sequentially maintained on a normal diet for three days at baseline, a low-salt diet for seven days (3 g/day, NaCl), then a high-salt diet for seven days (18 g/day). The concentration of plasma ghrelin was measured using an immunoenzyme method (ELISA). High-salt intake significantly increased fasting ghrelin levels, which were higher during the high-salt diet (320.7 ± 30.6 pg/mL) than during the low-salt diet (172.9 ± 8.9 pg/mL). The comparison of ghrelin levels between the different salt diets was statistically-significantly different (p < 0.01). A positive correlation between 24-h urinary sodium excretion and fasting ghrelin levels was demonstrated. Our data indicate that a high-salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity.

Effects of salt intake and potassium supplementation on renalase expression in the kidneys of Dahl salt-sensitive rats

Renalase is currently the only known amine oxidase in the blood that can metabolize catecholamines and regulate sympathetic activity. High salt intake is associated with high blood pressure (BP), possibly through the modulation of renalase expression and secretion, whereas potassium can reverse the high salt-mediated increase in blood pressure. However, whether potassium could also modulate BP through renalase is unclear. In this study, we aim to investigate how salt intake and potassium supplementation affect the level of renalase in rats. Eighteen salt-sensitive (SS) and 18 SS–13BN rats were divided into six groups, receiving normal salt (0.3% NaCl), high salt (8% NaCl) and high salt/potassium (8% NaCl and 8% KCl) dietary intervention for four weeks. At the end of experiments, blood and kidneys were collected for analysis. mRNA level of renalase was measured by quantitative real-time PCR and protein level was determined by Western blot. We found that mRNA and protein levels of renalase in the kidneys of SS and SS–13BN rats were significantly decreased (P < 0.05) after high salt intervention, whereas dopamine in plasma was increased (P < 0.05) compared with rats received normal salt, suggesting that salt may induce salt-sensitive hypertension through inhibition of renalase expression. We also found increased mRNA level and protein level of renalase, decreased catecholamine levels in plasma, and decreased BP in SS rats treated with high salt/potassium, compared with that of the high salt SS group. Taken together, the salt-induced increase and potassium-induced decrease in BP could be mediated through renalase. More studies are needed to confirm our findings and understand the underlying mechanisms.

Potassium supplementation ameliorates increased plasma homocysteine induced by salt loading in normotensive salt-sensitive subjects

ABSTRACT The mechanism by which high-salt and low-potassium diet contributes to hypertension remains poorly understood. Plasma homocysteine (Hcys) is recognized as a primary mediator of blood pressure (BP) response to some diets. Therefore, the present study tried to investigate whether plasma Hcys and BP could be regulated by salt loading in normotensive salt-sensitive (SS) persons, and further explored whether potassium supplementation could reverse the effect. We enrolled 47 normotensive subjects, aged 29–65 years. The protocol included 7 days on a low-salt diet (3g/day, NaCl), 7 days on a high-salt diet (18g/day), and then a high-salt diet with potassium supplementation (4.5g/day) for 7 days. After high-salt intake, BP was significantly increased and potassium supplementation lowered it in the SS group. Plasma Hcys were higher in SS subjects than in salt-resistant (SR) subjects after salt loading (34.4 ± 17.0 μmol/L versus 19.16 ± 6.4 μmol/L, P < 0.01). Plasma Hcys in SS subjects was increased on a high-salt diet than on a low-salt diet (34.4 ± 17.0 μmol/L versus 16.5 ± 8.3 μmol/L, P < 0.01), but plasma Hcys was ameliorated by potassium supplementation (34.4 ± 17.0 μmol/L versus 20.9 ± 10.4 μmol/L, P < 0.01). In SS subjects, the change of mean arterial blood pressure (MBP) correlated significantly and positively with the alteration of plasma Hcys during low-salt to high-salt intake and high-salt to high-salt with potassium supplementation (r = 0.75, P < 0.001; r = 0.74, P < 0.001, respectively). Our results indicate that Hcys may partly mediate the impact of high-salt intake and potassium supplementation on BP in SS subjects.