SUPPRESSION OF ANGⅡ AFTER ACUTE SALINE LOAD ASSOCIATED WITH THE CHANGES OF PLASMA ANP AND SODIUM METABOLISM IN SALT-SENSITIVE HYPERTENSION PATIENTS

Objective To observe the changes of plasma AngⅡ,ANP and their relationship with urine sodium excretion in salt sensitive hypertension. Methods The salt sensitivity was determined by acute saline loading test in 173 primary hypertensives of Stage Ⅰ or Stage Ⅱ. Plasma AngⅡand ANP was determined by radioimmunoassay. Results After acute salt load, AngⅡ was suppressed inadequately. The plasma ANP secretion was not increased. The urine sodiun excretion was delayed, Na + in RBC was increased in salt sensitive subjects. The plasma ANP was decreased in the salt sensitive subjects without AngⅡ suppressed. The 24 hours urine sodium excretion was lower than those AngⅡ suppressed.Conclusion The changes of plasma RAS are not homogeneous after salt load. Those without the plasma AngⅡ suppressed have more severe sodium metabolism abnormalities and the endogenous ANP secretion is impaired in salt sensitive patients.

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing. Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years. Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teena-gers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8 ±5.2 mmHg, P< 0.01; 12.2% ±12.0% vs. 2.5% ±4.4%, P< 0.001, respectively). There was a similar trend for diastolic blood pressure (8.4 ±6.4 mmHg vs. 3.7 ±6.4 mmHg, P= 0.052; 13.2% ±10.6 % vs. 6.8% ±10.1%, P= 0.053, respectively). Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.

RENAL ENDOGENOUS ET-1 AND URINARY SODIUM EXCRETION AND MICROALBUMINURIA IN HUMAN SALT-SENSITIVE HYPERTENSION

Objective To investigate the urinary endothelin-1 (ET-l ) excretion and urinary sodium excretion, microalbuminuria and ambulatory blood pressure(ABP) in salt-sensitive(SS) hypertension patients. Methods Twen- ty-one cases of normotensive subjects and 32 cases of uncomplicated hypertensive patients were recruited in this study. Salt sensitivity was determined by acute venous saline loading test. Before saline loading, 24-hour ABP mea- surements were performed. Urine samples were collected to assay ET-1,urinary sodium excretion and urinary albumin excretion(UAF). Results Compared to slat-resistant(SR) subgroup, SS showed low urinary ET-1 excretion in nor- motensive group (P<0.05) or hypertensive group (P<0.01),regardless or saline loading or not. The nighttime MAP of SS was higher than SR subgroup in normotensive or hypertensive group. Urinary sodium excretion during 4h of saline loading was significantly lower in SS than that in SR hypertensive patients (P<0.05). Twenty-four-hour UAE of SS patients was higher than SR group (P<0.01). Results of further correlation analysis indicated that the urinary ET-1 excretion was positively related to urinary sodium content and negatively to ABP and UAE. Conclusion Uri- nary ET-1 is low in SS normotensives or hypertension patients,which may play a role in renal sodium retention and renal impairment or SS hypertension patients.

A case-control study on the relationship between salt intake and salty taste and risk of gastric cancer

AIM: To investigate the relationship between salt intake and salty taste and risk of gastric cancer. METHODS: A 1:2 matched hospital based case-control study including 300 patients with gastric cancer and 600 cancer-free subjects as controls. Subjects were interviewed with a structured questionnaire containing 80 items, which elicited information on dietary, lifestyle habits, smoking and drinking histories. Subjects were tested for salt taste sensitivity threshold (STST) usingconcentrated saline solutions (0.22-58.4 g/L). Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CI). RESULTS: Alcohol and tobacco consumption increased the risk of gastric cancer [OR (95% CI) was 2.27 (1.27-4.04) for alcohol and 2.41 (1.51-3.87) for tobacco]. A protective effect was observed in frequent consumption of fresh vegetable and fruit [OR (95% CI) was 0.92 (0.58-0.98) for fresh vegetable and 0.87 (0.67-0.93) for fruit]. Strong association was found between STST ≥ 5 and gastric cancer [OR = 5.71 (3.18-6.72)]. Increased STST score was significantly associated with salted food intake and salty taste preference (P < 0.05). CONCLUSION: A high STST score is strongly associated with gastric cancer risk. STST can be used to evaluate an inherited characteristic of salt preference, and it is a simple index to verify the salt intake in clinic.

How far cardio metabolic and psychological factors affect salt sensitivity in normotensive adult population?

AIM To evaluate the prevalence of salt sensitivity and the impact of cardiometabolic and psychological characteristics on salt sensitivity in normotensive population. METHODS Of all participants,anthropometric measurements and fasting venous blood samples were collected,and study questionnaires were completed. Salt Sensitivity was defined based on the difference in mean arterial pressure with infusion of 2 L of normal saline followed by a low sodium diet and administration of three dosesof oral furosemide the day after. RESULTS Of 131 participants,56(42.7%) were diagnosed with salt sensitivity. Crude and age and sex adjusted regression analysis showed that low-density lipoprotein cholesterol and depression were positively associated with salt sensitivity(OR = 1.02,95%CI: 1.01-1.04 and OR = 1.15,95%CI: 1.00-1.34,respectively). CONCLUSION The high prevalence of salt sensitivity and its significant relation with prevalent risk factors necessitates considering its reduction actions at the population level and the need for further research.

Metabolomics signature of blood pressure salt sensitivity and its link to cardiovascular disease:A dietary salt-intervention trial

Individuals with a high degree of salt sensitivity(SS)have a greater risk of cardiovascular disease(CVD),but whether SS fosters CVD by influencing metabolomics homeostasis remains unclear.This study aimed to reveal the role of the SS-related metabolomics signature in the development of CVDs,based on the MetaSalt study,which was a dietary salt-intervention trial conducted at four centers in China in 2019.A total of 528 participants were recruited and underwent 3 days of baseline observations,a 10-day low-salt intervention,and a 10-day highsalt intervention.Plasma untargeted metabolomics,lipidomics,and BP measurements were scheduled at each stage.Participants were grouped into extreme SS,moderate SS,and salt-resistant(SR)individuals according to their BP responses to salt.Linear mixed models were used to identify SS-related metabolites and determine the relationship between the SS-related metabolomics signature and arterial stiffness.Mendelian randomization(MR)analyses were applied to establish the causal pathways among the SS-related metabolites,BP,and CVDs.Among the 713 metabolites,467 were significantly changed after the high-salt intervention.Among them,the changes in 30 metabolites from the low-salt to the high-salt intervention differed among the SS groups.Of the remaining nonsalt-related metabolites,the baseline levels of 11 metabolites were related to SS.These 41 metabolites explained 23%of the variance in SS.Moreover,SS and its metabolomics signature were positively correlated with arterial stiffness.MR analyses demonstrated that the SS-related metabolites may affect CVD risk by altering BP,indicating that the increase in BP was the consequence of the changes in SS-related metabolites rather than the cause.Our study revealed that the metabolomics signature of SS individuals differs from that of SR individuals and that the changes in SS-related metabolites may increase arterial stiffness and foster CVDs.This study provides insight into understanding the biology and targets of SS and its role in CVDs.

Characterization and Mapping of a Salt-Sensitive Mutant in Rice (Oryza sativa L.)

A salt-sensitive mutant designated rice salt sensitive 2 （rss2） was isolated from the M2 generation of the rice cultivar Nipponbare （Oryza sativa L. ssp. japonica） mutagenized with ethyl methanesulfonate （EMS）. This mutant exhibited a greater decrease in salt tolerance with a significant increase in Na＋ content in its shoots. Genetic analysis indicated that the increase in Na＋ in rss2 was controlled by a single recessive gene. Further genome-wide analysis of the linkage map constructed from the F2 population of rss2/Zhaiyeqing 8 （ZYQ8） showed that two quantitative trait loci （QTLs） on chromosomes 1 and 6 were responsible for the Na＋ concentration in shoots, which explained 14.5% and 53.3%, respectively, of the phenotypic variance. The locus on chromosome 1, but not that on chromosome 6, was also detected in the F2 population of Nipponbare/ZYQ8, suggesting that the QTL on chromosome 6 was responsible for the salt sensitivity in rss2. By analyzing the recombination events in 220 mutant individuals of an enlarged mapping population of rss2/ZYQ8, the rss2 locus was precisely mapped to an interval of 605.3 kb between insertion/deletion （InDel） markers IM21962 and IM22567. This finding will facilitate the cloning of the rss2 locus and provide insight into the physiological mechanisms of salt sensitivity in rice.

Sodium Stress in the Halophyte Thellungiella halophila and Transcriptional Changes in a thsos1-RNA Interference Line

The plasma membrane Na＋/H＋-antiporter salt overly sensitive1 （SOS1） from the halophytic Arabidopsis-relative Thellungiella halophila （ThSOS1） shows conserved sequence and domain structure with the orthologous genes from Arabidopsis thaliana and other plants. When expression of ThSOSt was reduced by RNA interference （RNAi）, pronounced characteristics of salt-sensitivity were observed. We were interested in monitoring altered transcriptional responses between Thellungiella wild type and thsost-4, a representative RNAi line with particular emphasis on root responses to salt stress at 350 mmol/L NaCI, a concentration that is only moderately stressful for mature wild type plants. Transcript profiling revealed several functional categories of genes that were differently affected in wild-type and RNAi plants. Down-regulation of SOS1 resulted in different gene expression even in the absence of stress. The pattern of gene induction in the RNAi plant under salt stress was similar to that of glycophytic Arabidopsis rather than that of wild type Thellungiella. The RNAi plants failed to down-regulate functions that are normally reduced in wild type Thellungiella upon stress and did not up-regulate functions that characterize the Thellungiella salt stress response. Metabolite changes observed in wild type Thellungiella after salt stress were less pronounced or absent in RNAi plants. Transcript and metabolite behavior suggested SOS1 functions including but also extending its established function as a sodium transporter. The down-regulation of ThSOS1 converted the halophyte Thellungiella into a salt-sensitive plant.