Wen-Ling Zheng

Association of Renalase SNPs rs2296545 and rs2576178 with the Risk of Hypertension: A Meta-Analysis

Background/Aims Two renalase single nucleotide polymorphisms (SNPs) rs2296545 and rs2576178 have been reported to be associated with the susceptibility to hypertension (HT). Given the inconsistent results, we conducted a meta-analysis to assess the association between these two SNPs and the risk of HT. Methods Electronic databases were systematically searched to find relevant studies. Subgroup analysis was conducted according to the different concomitant diseases and ethnicities in the study population. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed-effect or random-effect models. Results A total of six case–control studies on rs2296545 and six studies on rs2576178 were included. In the combined analysis, results showed a significant association between SNP rs2296545 and risk of HT in all genetic models (dominant model CG+CC/GG: OR = 1.43, 95% CI = 1.24–1.65; recessive model CC/CG+GG: OR = 1.36, 95% CI = 1.09–1.69; codominant model CC/GG: OR = 1.63, 95% CI = 1.20–2.20, CG/GG: OR = 1.30, 95% CI = 1.12–1.52; allelic model C/G: OR = 1.29, 95% CI = 1.10–1.51). In subgroup analysis, we observed a significant association between rs2296545 and risk of essential HT. Although we did not observe an association between rs2576178 polymorphism and HT in the combined analysis, an increased risk was observed in the essential HT patients versus healthy controls (subgroup 1) analysis under the dominant, recessive, and codominant genetic models. Conclusions Renalase gene rs2296545 polymorphism is significantly associated with increased risk of HT, whereas rs2576178 polymorphism may not be associated with the susceptibility to HT.

Effects of Renin-Angiotensin System Inhibitors on Renal Expression of Renalase in Sprague-Dawley Rats Fed With High Salt Diet

Background/Aims: The aim of our study was to investigate the effect of high-salt diet on the renal expression of renalase and the potential role of the local renin-angiotensin system in this process. Methods: Sprague-Dawley (SD) rats were divided into groups according to salt content in diet and drug treatment as follows: normal-salt diet (NS), high-salt diet (HS), high-salt intake with hydralazine (HS+H), high-salt diet with enalapril (HS+E), and high-salt diet with valsartan (HS+V). The dietary intervention and drugs were given for four weeks. Renin activity and angiotensin II type 1 receptor (AT1R) levels were detected by real-time PCR. Renalase mRNA and protein were also measured. Results: After four weeks, systolic blood pressure and proteinuria were significantly increased in the HS group with respect to the NS group. Dietary salt intake caused a dramatic decrease in renalase expression in the rat kidneys. Renal cortex renin and AT1R increased significantly in the HS and HS+H groups. Urinary protein was positively correlated with renal renin and AT1R levels. However, in the HS+E and HS+V groups, enalapril and valsartan failed to influence renal renalase expression but abolished the increase in proteinuria, renal cortex renin, and AT1R levels with respect to the HS group. Conclusion: This study indicates that high salt intake reduces renal expression, and renal RAS may be not involved in the regulation of renalase in SD rats fed with high-salt diet.

The Role of Uric Acid in Hypertension of Adolescents, Prehypertension and Salt Sensitivity of Blood Pressure

Uric acid is the end product of purine metabolism. Metabolic disorders of uric acid are associated with many disease states. Substantial evidence suggests the possible role of uric acid as a mediator of high blood pressure. Elevated uric acid is closely associated with new onset essential hypertension in adolescents and prehypertension; and urate-lowering agents can significantly improve these early stages of hypertension. Uric acid also influences salt sensitivity of blood pressure through two phases. Local renin-angiotensin-aldosterone system activation initiates renal damage, arteriolopathy, and endothelium dysfunction, which is followed by the dysregulation of sodium homeostasis, thereby leading to increased salt sensitivity. In this review we summarize the available evidence to contribute to a better understanding of the casual relationship between uric acid and early or intermediate stages of hypertension. We hope our review can contribute to the prevention of hypertension or provide new insights into a treatment that would slow the progression of hypertension.

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.

Effect of Salt Intake on Plasma and Urinary Uric Acid Levels in Chinese Adults: An Interventional Trial

Uric acid (UA) has been proposed as an important risk factor for cardiovascular and renal morbidity. We conducted an interventional trial to assess effects of altered salt intake on plasma and urine UA levels and the relationship between UA levels and salt sensitivity in humans. Ninety subjects (18–65 years old) were sequentially maintained on a normal diet for 3 days at baseline, a low-salt diet for 7 days (3.0 g/day, NaCl), and a high-salt diet for an additional 7 days (18.0 g/day of NaCl). Plasma UA levels significantly increased from baseline to low-salt diet and decreased from low-salt to high-salt diet. By contrast, daily urinary levels of UA significantly decreased from baseline to low-salt diet and increased from low-salt to high-salt diet. The 24 h urinary sodium excretions showed inverse correlation with plasma UA and positive correlation with urinary UA excretions. Additionally, salt-sensitive subjects presented significantly higher plasma UA changes in comparison to salt-resistant subjects, and a negative correlation was observed between degree of salt sensitivity and plasma UA difference. The present study indicates that variations in dietary salt intake affect plasma and urine UA levels, and plasma UA may be involved in pathophysiological process of salt sensitivity.

The responses of the inflammatory marker, pentraxin 3, to dietary sodium and potassium interventions

Pentraxin‐3 is a sensitive marker of inflammation that plays dual roles, pathogenic and cardioprotective, in the progression of cardiovascular diseases. Inflammation is intimately involved in salt‐induced hypertension. We investigated the responses of pentraxin‐3 to sodium and potassium supplementation to elucidate the potential role of pentraxin‐3 in salt‐induced hypertension. A total of 48 participants from northwest China were enrolled. All participants were maintained on a 3‐day normal diet, which was sequentially followed by a 7‐day low‐sodium diet, a 7‐day high‐sodium diet, and a 7‐day high‐sodium plus potassium diet. Plasma concentrations of pentraxin‐3 were assessed using ELISA. Plasma pentraxin‐3 decreased significantly during the low‐salt period compared to baseline (0.57 ± 0.19 ng/mL vs 0.72 ± 0.33 ng/mL, P = .012) and increased during the high‐salt period (0.68 ± 0.26 ng/mL vs 0.57 ± 0.19 ng/mL, P = .037). Potassium supplementation inhibited salt‐induced increase in pentraxin‐3 (0.56 ± 0.21 ng/mL vs 0.68 ± 0.26 ng/mL, P = .015). Ln‐transformed pentraxin‐3 at baseline was inversely correlated with BMI (r = −.349, P = .02), DBP (r = −.414, P = .005), MAP (r = −.360, P = .017). We found a positive correlation between the ln‐transformed concentrations of pentraxin‐3 and 24‐hour urinary sodium during low and high Na+ periods (r = .269, P = .012) and a negative relationship with 24 hours urinary potassium excretion during high‐salt and high‐salt plus potassium periods (r = −.246, P = .02). These correlations remained significant after adjusting for confounders. Pentraxin‐3 responses were more prominent in salt‐sensitive individuals than salt‐resistant individuals. Dietary salt and potassium interventions significantly altered circulating pentraxin‐3.

Association between urinary sodium excretion and uric acid, and its interaction on the risk of prehypertension among Chinese young adults

High uric acid (UA) level and high salt intake are reportedly associated with cardiovascular disease. This study investigated the association between UA and urinary sodium excretion, as well as its interaction on the risk of prehypertension. A total of 1869 participants without hypertension were recruited from a previously established cohort in Shaanxi Province, China. The participants were classified as normotensive or prehypertensive on the basis of their blood pressure. Increasing quartiles of sodium excretion were associated with high urinary UA/creatinine levels in prehypertensive participants. Estimated sodium excretion positively correlated with urinary UA/creatinine excretions in the prehypertensive group. In addition, the multivariate-adjusted odds ratios for prehypertension compared with normotension were 1.68 (1.27–2.22) for sodium excretion and 1.71 (1.21–2.42) for serum UA. Increasing sodium excretion and serum UA were associated with higher risk of prehypertension. Compared with the lowest quartiles, the highest sodium excretion and serum UA quartiles entailed 3.48 times greater risk of prehypertension. Sodium excretion is associated with urinary UA excretion in prehypertensive participants. The present study shows that high levels of salt intake and serum UA simultaneously are associated with a higher risk of prehypertension.

The Relationships of the Fractional Excretion of Uric Acid with Brachial-Ankle Pulse Wave Velocity and Ankle Brachial Index in Chinese Young Adults

Background/Aims: Elevated serum uric acid (UA) was intimately correlated with vascular stiffness and abnormal ankle brachial index (ABI) in various populations. These correlations lost significance after adjustment for estimated glomerular filtration rate (eGFR), indicating that the association of UA and brachial-ankle pulse wave velocity (baPWV) or ABI might be driven by kidney function. UA is predominantly eliminated through the kidneys, and metabolic disorders can influence the clearance of UA. In this study, we aimed to explore the putative correlation between FEUA and baPWV or ABI to determine to what extent the associations with UA were affected by renal function. Methods: This cross-sectional study enrolled 2351 participants, who underwent general health screening in Hanzhong people’s hospital from March to June of 2017. BaPWV and ABI were measured using a volume-plethysmographic apparatus (BP-203RPEII; Nihon Colin, Tokyo, Japan). FEUA was divided into quartiles: Q1:FEUA≤3.07; Q2: 3.07 9.19. Results: Lower FEUA predicted a higher prevalence of high baPWV and low ABI (p for trend <0.001). The respective ORs for high baPWV from the first to the third quartiles of FEUA were 1.777(1.323, 2.387); 1.561(1.158, 2.104); and 1.680 (1.250, 2.259). The prevalence of low ABI was greatly elevated with the decrement of FEUA [ORs for the first to third FEUA quartiles were 6.977(2.062, 23.610); 5.123(1.475, 17.790); and 2.685(0.709, 10.171), respectively]. The association of FEUA and ABI was independent of related confounding factors. However, the association between FEUA and baPWV was greatly influenced by corresponding confounders, especially gender. The efficacy of FEUA in the prediction of low ABI was stronger than that of serum UA. However, serum UA was more powerful in the prediction of high baPWV. Conclusion: Kidney function exerted a profound influence on the relationship between UA and baPWV or ABI, revealing complex interactions among cardiovascular risk factors.

EFFECT OF SALT INTAKE ON PLASMA AND URINARY URIC ACID LEVELS IN CHINESE ADULTS: AN INTERVENTIONAL TRIAL

Objective: Uric acid (UA) has been proposed as an important risk factor for cardiovascular and renal morbidity. We conducted an interventional trial to assess the effects of altered salt intake on plasma and urine UA levels and the relationship between UA levels and salt sensitivity in humans. Design and method: Ninety subjects (18–65 years old) were selected from a rural community in Northern China in our interventional study. All subjects were sequentially maintained on a normal diet for 3 days at baseline, on a low-salt diet for 7 days (3.0 g/day, NaCl), and on a high-salt diet for an additional 7 days (18.0 g/day of NaCl). Results: Plasma UA levels significantly increased from baseline to low-salt diet (262.7 ± 7.6 vs. 280.0 ± 7.4 &mgr;mol/L, P < 0.001) and decreased from low-salt to high-salt diet (280.0 ± 7.4 vs. 242.6 ± 7.1 &mgr;mol/L, P < 0.001). By contrast, daily urinary levels of UA significantly decreased from baseline to low-salt diet (2,242.4 ± 168.3 vs. 1,558.2 ± 101.1 &mgr;mol/24 h, P < 0.001) and increased from low-salt to high-salt diet (1,558.2 ± 101.1 vs. 1,761.9 ± 90.2 &mgr;mol/24 h, P = 0.032). The 24 h urinary sodium excretions showed inverse correlation with plasma UA (r = −0.258, P < 0.001) and positive correlation with urinary UA excretions (r = 0.176, P = 0.019). Additionally, as shown in Figure, salt-sensitive subjects presented significantly higher plasma UA changes in comparison to salt-resistant subjects (low salt response: 34.9 ± 7.8 vs. 12.5 ± 4.8 &mgr;mol/L, P = 0.028; high salt response: −52.5 ± 7.7 vs. −33.4 ± 4.1 &mgr;mol/L, P = 0.034), and a negative correlation was observed between degree of salt sensitivity and plasma UA difference. Figure. No caption available. Conclusions: The present study indicates that variations in dietary salt intake affect plasma and urine UA levels, and plasma UA may be involved in the pathophysiological process of salt sensitivity.

Effect of Salt Intake on Serum Glucagon-Like Peptide-1 Levels in Normotensive Salt-Sensitive Subjects

Background/Aims: Excess dietary salt is a critical risk factor of salt-sensitive hypertension. Glucagon-like peptide-1 (GLP-1) , a gut incretin hormone, conferring benefits for blood pressure by natriuresis and diuresis. We implemented a randomized trial to verify the effect of altered salt intake on serum GLP-1 level in human beings. Methods: The 38 subjects were recruited from a rural community of Northern China. All subjects were sequentially maintained a baseline diet period for 3 days, a low-salt diet period for 7 days (3.0g/day of NaCl) , and a high-salt diet period for additional 7 days (18.0g/day of NaCl). Results: Serum GLP-1 level increased significantly with the change from the baseline period to the low-salt diet period and decreased with the change from the low-salt to high-salt diet in normotensive salt-sensitive (SS) but not salt-resistant (SR) individuals. There was a significant inverse correlation between the serum GLP-1 level and the MAP in SS subjects. Inverse correlation between the serum GLP-1 level and 24-h urinary sodium excretion was also found among different dietary interventions in SS subjects. Conclusions: Our study indicates that variations in dietary salt intake affect the serum GLP-1 level in normotensive salt-sensitive Chinese adults.