Effects of salt loading and potassium supplement on the circadian blood pressure profile in salt-sensitive Chinese patients.

BACKGROUND AND OBJECTIVE: Salt-sensitive (SS) patients more frequently showed a nondipper blood pressure pattern and were associated with more serious target organ damage than non-SS patients. We aimed to investigate whether potassium supplement can improve the blunted nocturnal blood pressure fall in SS patients exposed to a high-salt diet. PATIENTS AND METHODS: Approximately 49 normotensive and mildly hypertensive Chinese patients received a study protocol of a 3 days of baseline examination, 7 days of a low-salt diet (3 g NaCl/day), 7 days of a high-salt diet (18 g NaCl/day), and 7 days of a high-salt diet with a potassium supplement (18 g NaCl and 4.5 g KCl/day). The 24 h ambulatory blood pressure was determined at the end of each period. RESULTS: A total of 14 patients were classified as SS according to the at least 10% increase in their 24-h mean arterial pressure after high-salt loading. The night-to-day blood pressure ratio was significantly higher in SS patients than in non-SS patients during the high-salt loading period (systolic 0.96±0.01 vs. 0.89±0.01, P<0.01; diastolic 0.96±0.01 vs. 0.92±0.01, P<0.05). Compared with the high-salt loading period, the night-to-day blood pressure ratio was significantly reversed by potassium supplement in SS patients (systolic 0.91±0.01 vs. 0.96±0.01, P<0.05; diastolic 0.91±0.01 vs. 0.96±0.01, P<0.05). CONCLUSION: Potassium supplement can improve the blunted nocturnal blood pressure fall in SS patients exposed to a high-salt diet, but the related mechanism needs to be studied further.

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.

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 51.3 mmol/day of sodium), a seven-day high-sodium diet (18 g/day of NaCl or 307.8 mmol/day of sodium) and a seven-day high-sodium plus potassium supplementation intervention (4.5 g/day of KCl or 60 mmol/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.

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.

Effect of salt intake and potassium supplementation on serum renalase levels in Chinese adults: a randomized trial.

Renalase, 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.

Adenine sulfate improves cardiac function and the cardiac cholinergic system after myocardial infarction in rats.

Recent studies have shown that vagal activation may have an important therapeutic implication for myocardial infarction (MI), but effective strategies remain unexplored. Here, we investigate whether adenine sulfate can preserve cardiac function and the cholinergic system against MI. Rats were treated with adenine sulfate for three weeks after coronary ligation. Cardiac function was assessed by hemodynamics. The muscarinic M(2) receptor and cholinesterase-positive nerves were semi-quantified by immunochemical and histochemical staining. The maximal binding capacity (B(max)) of muscarinic receptors, determined by radioligand binding assay, showed that cardiac function was impaired in MI rats. Adenine sulfate reversed MI-induced reduction of mean artery pressure and left ventricular systolic pressure and elevation of left ventricular end-diastolic pressure. Moreover, adenine sulfate also increased nitric oxide (NO) and nitric oxide synthase (NOS) activity. The amelioration was accompanied by a reversal of the infarction-induced reduction of cholinesterase-positive nerves and M(2)-receptor expression and B(max) in the adenine sulfate high dose group. Meanwhile, adenine sulfate treatment corrected the disorder of cardiac redox state by reduction in maleic dialdehyde and increase in superoxide dismutase. In conclusion, adenine sulfate exerts cardioprotection against MI and ameliorates NO production. Changes in cardiac vagal distribution density and M(2)-receptor expression raise the possibility that improvement of the cardiac cholinergic system is involved in adenine sulfate-induced cardioprotective effects.