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High levels of soil salinity inhibit the growth of legumes such as soybeans, significantly reducing their productivity. This research aimed to assess the salt tolerance of soybean genotypes by evaluating seed germination at varying salt concentrations (100 mM, 150 mM, and 200 mM NaCl) from two seed source locations. A total of 198 soybean genotypes were analyzed post-germination using 10 quantitative traits: germination percentage, seedling fresh weight, seedling dry weight, seedling length, shoot length, root length, seedling vigor index-1, seedling vigor index-2, seedling water content, and salt tolerance. Analysis of variance (ANOVA) results indicated significant differences among treatments across both locations. Principal component analysis revealed that certain quantitative traits were more prominent at different salt concentrations, thus confirming varied responses to salt stress. Correlation analysis demonstrated a positive relationship between germination percentages and growth parameters such as fresh weight, dry weight, and vigor index. The study observed a decline in all quantitative traits as salt concentration increased, highlighting the stress experienced by plants during germination and growth under high salinity conditions. Using K-means clustering, the 198 genotypes were categorized into tolerant, moderately tolerant, moderately susceptible, and susceptible groups. This clustering helped identify genotypes exhibiting high tolerance (≥ 80% germination at 200 mM NaCl) and high susceptibility (≤ 40% germination at 100 mM NaCl) consistently across both seed source locations. Consequently, seven salt-tolerant genotypes (MACS 708, KALITUR, MACS 1037, IC 13050, MACS 1010, PK 1029, and MACS 173) and three salt-sensitive genotypes (HIMSO 1563, EC 391181, and EC 241920) were identified, providing new insights into soybean cultivation under saline conditions. [ABSTRACT FROM AUTHOR]

Salt stress is an environmental factor that limits plant seed germination, growth, and survival. We performed a comparative RNA sequencing transcriptome analysis during germination of the seeds from two cultivars with contrasting salt tolerance responses. A transcriptomic comparison between salt-tolerant cotton cv Jin-mian 25 and salt-sensitive cotton cv Su-mian 3 revealed both similar and differential expression patterns between the two genotypes during salt stress. The expression of genes related to aquaporins, kinases, reactive oxygen species (ROS) scavenging, trehalose biosynthesis, and phytohormone biosynthesis and signaling that include ethylene (ET), gibberellin (GA), abscisic acid (ABA), jasmonic acid (JA), and brassinosteroid (BR) were systematically investigated between the cultivars. Despite the involvement of these genes in cotton's response to salt stress in positive or negative ways, their expression levels were mostly similar in both genotypes. Interestingly, a PXC2 gene (Ghir_D08G025150) was identified, which encodes a leucine-rich repeat receptor-like protein kinase (LRR-RLK). This gene showed an induced expression pattern after salt stress treatment in salt-tolerant cv Jin-mian 25 but not salt-sensitive cv Su-mian 3. Our multifaceted transcriptome approach illustrated a differential response to salt stress between salt-tolerant and salt-sensitive cotton. [ABSTRACT FROM AUTHOR]

In this work, an anisotropic constitutive model for equilibrium swelling of cellulose-reinforced salt-sensitive hydrogels is proposed and its capability is verified using the experimental data. This model is able to predict the swelling behavior of salt-sensitive hydrogels reinforced with fibers in different types of orientation such as perfectly aligned, uniform in-plane, and uniform volumetric. The model is implemented numerically in the finite element method framework. Several related parameters i.e., swelling ratio, principal stretches, true concentration of counter-ion and co-ion, and salt concentration are investigated both analytically and through finite element method (FEM). Good agreement between the analytical and numerical results indicates that the model can be used for simulating more complex structures including multi-layer strips and sheets. The results show that adding cellulose fibers to the hydrogel's medium leads to a significant enhancement in the strength of the material while preserving the inherent flexibility of the hydrogel. [ABSTRACT FROM AUTHOR]

Abdominal adhesions are a class of serious complications following abdominal surgery, resulting in a complicated and severe syndrome and sometimes leading to a Gordian knot. Traditional therapies employ hydrogels synthesized using complicated chemical formulations-often with click chemistry or thermal responsive hydrogel. The complicated synthesis process and severe conditions limit the extent of the hydrogels' applications. In this work, poly 3-[2-(methacryloyloxy)ethyl](dimethyl)-ammonio]-1-propanesulfonate (PSBMA) polymer was synthesized to self-assemble into physical hydrogels due to the inter- and intramolecular ion interactions. The strong static interaction bonding density has a substantial impact on the gelation and physicochemical properties, which is beneficial to clinical applications and offers a novel way to obtain the desired hydrogel for a specific biomedical application. Intriguingly, this PSBMA polymer can be customized into a transient network with outstanding antifouling capability depending on the ion concentration. As ion concentration increases, the PSBMA hydrogel dissociated completely, endowing it as a candidate for adhesion prevention. In the cecum-sidewall model, the PSBMA hydrogel demonstrated superior anti-adhesion properties than commercial HA hydrogel. Furthermore, we have demonstrated that this PSBMA hydrogel could inhibit the inflammatory response and encourage anti-fibrosis resulting in adhesion prevention. Most surprisingly, the recovered skins of cecum and sidewall are as smooth as the control skin without any scar and damage. In conclusion, a practical hydrogel was synthesized using a facile method based on purely zwitterionic materials, and this ion-sensitive, antifouling adjustable supramolecular hydrogel with great clinic transform potential is a promising barrier for preventing postoperative tissue adhesion. The development of hydrogels with satisfactory coverage, long retention time, facile synthetic method, and good biocompatibility is vital for preventing peritoneal adhesions. Herein, we developed a salt sensitive purely zwitterionic physical hydrogel poly 3-[2-(methacryloyloxy)ethyl](dimethyl)-ammonio]-1-propanesulfonate (PSBMA) hydrogel to effectively prevent postoperative and recurrent abdominal adhesions. The hydrogel was simple to synthesize and easy to use. In the cecum-sidewall model, PSBMA hydrogel could instantaneously adhere and fix on irregular surfaces and stay in the wound for more than 10 days. The PSBMA hydrogel could inhibit the inflammatory response, encourage anti-fibrosis, and restore smoothness to damaged surfaces resulting in adhesion prevention. Overall, the PSBMA hydrogel is a promising candidate for the next generation of anti-adhesion materials to meet clinical needs. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Salinity is a complex environmental stress that affects the growth and production of rice worldwide. But there are some rice landraces in coastal regions that can survive in presence of highly saline conditions. An understanding of the molecular attributes contributing to the salinity tolerance of these genotypes is important for developing salt-tolerant high yielding modern genotypes to ensure food security. Therefore, we investigated the role and functional differences of two K+ salt-responsive transporters. These are OsTPKa or Vacuolar two-pore potassium channel and OsHAK_like or a hypothetical protein of the HAK family. These transporters were selected from previously identified QTLs from the tolerant rice landrace genotype (Horkuch) and sensitive genotype (IR29). Methods: In silico comparative sequence analysis of the promoter sequences of two these genes between Horkuch and IR29 was done. Real-Time expression of the selected genes in leaves and roots of IR29 (salt-sensitive), I-14 and I-71 (Recombinant Inbred Lines of IR29(♀)× Horkuch), Horkuch and Pokkali (salt-tolerant) under salt-stress at different time points was analyzed. For further insight, OsTPKa and OsHAK_like were chosen for loss-of-function genomic analysis in Horkuch using the CRISPR/Cas9 tool. Furthermore, OsTPKa was chosen for cloning into a sensitive variety by Gateway technology to observe the effect of gain-of-function. Results: The promoter sequences of the OsTPKa and OsHAK_like genes showed some significant differences in promoter sequences which may give a survival advantage to Horkuch under salt-stress. These two genes were also found to be overexpressed in tolerant varieties (Horkuch and Pokkali). Moreover, a coordinated expression pattern between these two genes was observed in tolerant Horkuch under salt-stress. Independently transformed plants where the expression of these genes was significantly lowered, performed poorly in physiological tests for salinity tolerance. On the other hand, positively transformed T0 plants with the OsTPKa gene from Horkuch consistently showed growth advantage under both control and salt stress. Discussion: The poor performance of the transgenic plants with the downregulated genes OsTPKa and OsHAK_like under salt stress supports the assumption that OsTPKa and OsHAK_like play important roles in defending the rice landrace Horkuch against salt stress, minimizing salt injury, and maintaining plant growth. Moreover, the growth advantage provided by overexpression of the vacuolar OsTPKa K+ transporter, particularly under salt stress reconfirms its important role in providing salt tolerance. The QTL locus from Horkuch containing these two transporters maybe bred into commercial rice to produce high-yielding salt tolerant rice. [ABSTRACT FROM AUTHOR]

Salt‐induced hypertension is one of the major issues worldwide and one of the main factors involved in heart and kidney failure. The objective of this study was to investigate the potential role of Benincasa hispida extracts on high salt‐induced hypertension in Dahl‐salt sensitive (D‐SS) rats and to find out the metabolic and biochemical pattern involved in the reduction of hypertension. Twenty‐six Dahl salt‐sensitive (D‐SS) rats were selected and divided into four groups. The metabolic strategy was applied to test the extracts on salt‐sensitive hypertension in kidney. Gas Chromatography–Mass spectrometry (GC–MS) was used to identify the potent biochemical profile in renal medulla and cortex of rat kidneys. The differential metabolites of cortex and medulla, enrichment analysis and pathway analysis were performed using metabolomics data. The GC–MS data revealed that 24 different antihypertensive metabolites was detected in renal cortex, while 16 were detected in renal medulla between different groups. The significantly metabolic pathways namely citrate cycle, glutathione metabolism, glycine, serine, and threonine metabolism, glyoxylate and dicarboxylate metabolism, glycerolipid metabolism, alanine, aspartate and glutamate metabolism in renal cortex and glycerolipid metabolism, pentose phosphate pathway, citrate cycle, glycolysis, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis in renal medulla were involved in the process of Hypertension. The results suggest that the extract mainly alter the metabolic pathways of amino acid in Dahl salt‐sensitive rats and its antioxidant potential reduced the hypertension patterns of Salt‐sensitive rat. The antihypertensive components malic acid, aspartic acid, and glycine of extract can be used as therapeutic drugs to protect kidneys from salt‐induced hypertension. Practical applications: Hypertension is a multifactorial disease and one of the risk factors for heart and kidney failure. Benincasa hispida is a widely used vegetable in China, which belongs to the Cucurbitaceae family. Benincasa hispida (wax gourd) has been used in traditional Chinese medicine for the treatment of inflammation and hypertension. The Benincasa hispida contains many compounds such as amino acids, carbohydrates, volatile compounds, vitamins, and minerals. The amino acid present in the pulp of Benincasa hispida are ornithine, threonine, aspartate, glutamate, serine, glycine, proline, alanine, valine, cysteine, isoleucine, tyrosine, leucine, lysine, phenylalanine, histidine, arginine, and γ‐aminobutyric acid. Our results showed that Benincasa hispida is one of the potent natural antioxidants and can maintain normal blood pressure in Dahl salt‐sensitive rats (D‐SS). In conclusion, the current results provide good theoretical basis for the development and research using Benincasa hispida as an effective natural antioxidant for hypertension. [ABSTRACT FROM AUTHOR]

Blood pressure (BP) is influenced by genetic variation and sodium intake with sex-specific differences; however, studies to identify renal molecular mechanisms underlying the influence of sodium intake on BP in nonhuman primates (NHP) have focused on males. To address the gap in our understanding of molecular mechanisms regulating BP in female primates, we studied sodium-naïve female baboons (n = 7) fed a high-sodium (HS) diet for 6 wk. We hypothesized that in female baboons variation in renal transcriptional networks correlates with variation in BP response to a high-sodium diet. BP was continuously measured for 64-h periods throughout the study by implantable telemetry devices. Sodium intake, blood samples for clinical chemistries, and ultrasound-guided kidney biopsies were collected before and after the HS diet for RNA-Seq and bioinformatic analyses. We found that on the LS diet but not the HS diet, sodium intake and serum 17 β-estradiol concentration correlated with BP. Furthermore, kidney transcriptomes differed by diet-unbiased weighted gene coexpression network analysis revealed modules of genes correlated with BP on the HS diet but not the LS diet. Our results showed variation in BP on the HS diet correlated with variation in novel kidney gene networks regulated by ESR1 and MYC; i.e., these regulators have not been associated with BP regulation in male humans or rodents. Validation of the mechanisms underlying regulation of BP-associated gene networks in female NHP will inform better therapies toward greater precision medicine for women. [ABSTRACT FROM AUTHOR]

Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases and the leading cause of premature death worldwide. However, the pathogenesis of the hypertension, especially essential hypertension, is complex and requires in-depth studies. Recently, new findings about essential hypertension have emerged, and these may provide important theoretical bases and therapeutic tools to break through the existing bottleneck of essential hypertension. In this review, we demonstrated important advances in the different pathogenesis areas of essential hypertension, and highlighted new treatments proposed in these areas, hoping to provide insight for the prevention and treatment of the essential hypertension.

Current knowledge of the link between microbiota and hypertension is limited to the gut. Besides the gut, oral cavity and skin are other locations where sodium chloride (NaCl) is in direct contact with microbiota. Although oral nitrate-reducing bacteria generate nitric oxide, which leads to vasodilation and lowering of blood pressure (BP), the skin excretes sodium via sweat glands and is an important site for sodium and BP homeostasis. However, knowledge on the contributions of oral and skin microbiota to BP regulation, is limited. Therefore, the current study was conducted to compare the tripartite relationship between site, sex, and genetic effects on the composition of oral, skin, and gut microbiota impacting hypertension. Microbiota were profiled from the oral cavity, skin, and feces of both male and female hypertensive Dahl salt-sensitive (S) and congenic rats with genomic substitutions on rat chromosomes (RNO) 1, 5, 9, and 10, demonstrating disparate BP effects. Sex-specific differences in β-diversity were observed only in skin microbiota. The most abundant taxa of the oral and skin microbiota were Actinobacteria and Cyanobacteria, respectively. Oral Actinobacteria were inversely associated with BP. Although the abundance of oral Actinobacteria was upregulated by the BP locus on RNO10 in both sexes, depletion of skin Cyanobacteria decreased the protection from hypertension in the RNO5 female, but not male, congenic strain. In conclusion, to our knowledge this is the first study to identify specific microbiota in sites other than gut as contributors to BP regulation. Notably, both oral Actinobacteria and skin Cyanobacteria were beneficial for lowering BP. [ABSTRACT FROM AUTHOR]

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Angiotensin-converting enzyme 2 (ACE 2) in the heart including its sex dependency in the hypertensive heart, has not been much studied compared to ACE. In the present study, we used the Dahl salt-sensitive rat exposed to fructose and salt to model a hypertensive phenotype in males, females, and ovariectomized females. Blood pressure was measured by the tale-cuff technique in the conscious state. Expression of RAS-related genes ACE, ACE2, angiotensin II receptor type 1, Mas1, and CMA1 in the heart were quantified. The results revealed small but significant differences between male and female groups. The main results indicate the presence of a male preponderance for an increase in ACE and ACE2 gene expression. The results are in accordance with the role of androgens or male chromosomal complement in controlling the expression of the two ACE genes.

Angiotensin-converting enzyme 2 (ACE 2) in the heart including its sex dependency in the hypertensive heart, has not been much studied compared to ACE. In the present study, we used the Dahl salt-sensitive rat exposed to fructose and salt to model a hypertensive phenotype in males, females, and ovariectomized females. Blood pressure was measured by the tale-cuff technique in the conscious state. Expression of RAS-related genes ACE, ACE2, angiotensin II receptor type 1, Mas1, and CMA1 in the heart were quantified. The results revealed small but significant differences between male and female groups. The main results indicate the presence of a male preponderance for an increase in ACE and ACE2 gene expression. The results are in accordance with the role of androgens or male chromosomal complement in controlling the expression of the two ACE genes. [ABSTRACT FROM AUTHOR]

We discovered high Na+ and water content in the skin of newborn Sprague–Dawley rats, which reduced ~ 2.5-fold by 7 days of age, indicating rapid changes in extracellular volume (ECV). Equivalent changes in ECV post birth were also observed in C57Bl/6 J mice, with a fourfold reduction over 7 days, to approximately adult levels. This established the generality of increased ECV at birth. We investigated early sodium and water handling in neonates from a second rat strain, Fischer, and an Hsd11b2-knockout rat modelling the syndrome of apparent mineralocorticoid excess (SAME). Despite Hsd11b2−/− animals exhibiting lower skin Na+ and water levels than controls at birth, they retained ~ 30% higher Na+ content in their pelts at the expense of K+ thereafter. Hsd11b2−/− neonates exhibited incipient hypokalaemia from 15 days of age and became increasingly polydipsic and polyuric from weaning. As with adults, they excreted a high proportion of ingested Na+ through the kidney, (56.15 ± 8.21% versus control 34.15 ± 8.23%; n = 4; P < 0.0001), suggesting that changes in nephron electrolyte transporters identified in adults, by RNA-seq analysis, occur by 4 weeks of age. Our data reveal that Na+ imbalance in the Hsd11b2−/− neonate leads to excess Na+ storage in skin and incipient hypokalaemia, which, together with increased, glucocorticoid-induced Na+ uptake in the kidney, then contribute to progressive, volume contracted, salt-sensitive hypertension. Skin Na+ plays an important role in the development of SAME but, equally, may play a key physiological role at birth, supporting post-natal growth, as an innate barrier to infection or as a rudimentary kidney. [ABSTRACT FROM AUTHOR]

On average, black individuals are widely believed to be more sensitive than white individuals to blood pressure (BP) effects of changes in salt intake. However, few studies have directly compared the BP effects of changing salt intake in black versus white individuals. In this narrative review, we analyze those studies and note that when potassium intake substantially exceeds the recently recommended US dietary goal of 87 mmol/day, black adults do not appear more sensitive than white adults to BP effects of short-term or long-term increases in salt intake (from an intake ≤50 mmol/day up to 150 mmol/day or more). However, with lower potassium intakes, racial differences in salt sensitivity are observed. Mechanistic studies suggest that racial differences in salt sensitivity are related to differences in vascular resistance responses to changes in salt intake mediated by vasodilator and vasoconstrictor pathways. With respect to cause and prevention of racial disparities in salt sensitivity, it is noteworthy that 1) on average, black individuals consume less potassium than white individuals and 2) consuming supplemental potassium bicarbonate, or potassium rich foods can prevent racial disparities in salt sensitivity. However, the new US dietary guidelines reduced the dietary potassium goal well below the amount associated with preventing racial disparities in salt sensitivity. These observations should motivate research on the impact of the new dietary potassium guidelines on racial disparities in salt sensitivity, the risks and benefits of potassium-containing salt substitutes or supplements, and methods for increasing consumption of foods rich in nutrients that protect against salt-induced hypertension. [ABSTRACT FROM AUTHOR]

Background/Aims: The present study investigated whether the transient receptor potential melastatin 4 (TRPM4) channel plays a role in high salt diet (HSD)-induced endothelial injuries. Methods: Western blotting and immunofluorescence were used to examine TRPM4 expression in the mesenteric endothelium of Dahl salt-sensitive (SS) rats fed a HSD. The MTT, TUNEL, and transwell assays were used to evaluate the cell viability, cell apoptosis, and cell migration, respectively, of human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were used to determine the concentrations of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), and E-selectin. Carboxy-H2DCFDA, a membrane-permeable reactive oxygen species (ROS)-sensitive fluorescent probe, was used to detect intracellular ROS levels. Results: TRPM4 was mainly expressed near the plasma membrane of mesenteric artery endothelial cells, and its expression level increased in SS hypertensive rats fed a HSD. Its protein expression was significantly upregulated upon treatment with exogenous hydrogen peroxide (H2O2) and aldosterone in cultured HUVECs. Cell viability decreased upon treatment with both agents in a concentration-dependent manner, which could be partially reversed by 9-phenanthrol, a specific TRPM4 inhibitor. Exogenous H2O2 induced apoptosis, enhanced cell migration, and increased the release of adhesion molecules, including ICAM-1, VCAM-1, and E-selectin, all of which were significantly attenuated upon treatment with 9-phenanthrol. Aldosterone and H2O2 induced the accumulation of intracellular ROS, which was significantly inhibited by 9-phenanthrol, suggesting that oxidative stress is one of the mechanisms underlying aldosterone-induced endothelial injury. Conclusions: Given the fact that oxidative stress and high levels of circulating aldosterone are present in hypertensive patients, we suggest that the upregulation of TRPM4 in the vascular endothelium may be involved in endothelial injuries caused by these stimuli.

Masanori Harada,1 Taro Takeshima,2 Masanobu Okayama,2,3 Eiji Kajii,21Department for Support of Rural Health Care, Yamaguchi Grand Medical Center, Hofu, Yamaguchi, 2Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Shimotsuke, 3Division of Community Medicine and Medical Education, Kobe University Graduate School of Medicine, Kobe, Japan Purpose: To identify the differences in genotype frequencies of salt-sensitive genes between residents of fishing communities (FCs) and nonfishing communities (NFCs). Methods: The subjects included 18,156 individuals (8,043 males [44%] and 10,113 females [56%]; average age: 57.2±16.1 years) from the general population who were registered with large-scale genome banks and resided in 30 prefectures and 78 different regions in Japan. The measurement items were age, sex, blood pressure, presence or absence of hypertension, body mass index, alcohol consumption, and smoking habit. Furthermore, to analyze the genotype frequencies of salt-sensitive genes, α-adducin 1 (ADD1), angiotensinogen (AGT), angiotensin II receptor type 1 (AT1), and guanine nucleotide-binding protein β peptide 3 (GNB3) were measured. According to the 2004 government classification of municipalities (cities, towns, and villages), communities existing in areas bordering an ocean and with an ocean port were defined as FCs (28 areas). The others were defined as NFCs (50 areas). A logistic regression model was used for comparison of genotype frequencies between subjects residing in FCs and NFCs. Results: Of the included subjects, 4,916 (27.0%) and 13,240 (73.0%) resided in FCs and NFCs, respectively. In FCs, the mean age was 59.4±16.7 years and men accounted for 41.0% of the cohort (n=2,015). In NFCs, the mean age was 56.4±15.8 years and men accounted for 45.5% of the cohort (n=6,028). The adjusted odds ratios of the AA and AG genotypes compared with the GG genotype for AGT were 0.80 (95% confidence interval [CI]: 0.68–0.95) and 0.76 (95% CI: 0.64–0.91), respectively. The adjusted odds ratio of the CC genotype compared with AA for AT1 was 0.63 (95% CI: 0.40–0.93). Conclusion: The incidence of the salt-sensitive genotypes AGT and AT1 in residents of FCs were significantly lower than in NFCs.Keywords: salt-sensitive, hypertension, single-nucleotide polymorphisms, regional difference, lifestyle, behavior

Aim. To investigate an ability of HBD-2 to induce aggregation of erythrocytes. Methods. Aggregation assay, turbidimetry, light microscopy. Results. We have identified aggregation of erythrocytes in the presence of at least 12.5 μM HBD-2 that was confirmed by light microscopy. Effect was strongly depended on HBD-2 concentration but was masked by hemolysis of erythrocytes. Also, aggregation was diminished in presence even 10 mM of NaCl that may indicate electrostatic nature of interactions between HBD-2 and erythrocytes. Conclusions. HBD-2 can induce the salt-sensitive aggregation of erythrocytes in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Graft copolymers based on carboxymethylcellulose (CMC) and thermosensitive polyetheramines (ethylene oxide/propylene oxide = 33/10 and 1/9) were prepared in water, at room temperature, by using a carbodiimide and N -hydroxysuccinimide as activators. SLS was applied to obtain M w , A 2 and R g of CMC and its derivatives. Amide linkages were evidenced by FTIR and grafting percentage was determined by 1 H NMR. TGA demonstrated that copolymers were thermally more stable than their precursors. DLS, UV-vis and rheological measurements revealed that properties were salt- and thermo-responsive and linked to the polysaccharide/polyetheramine ratio and the hydrophobicity of the graft. None of the copolymers showed cloud point temperature (Tcp) in water, but they turned turbid in saline media when heated. Copolymers exhibited thermothickening behaviour at 60 °C (>Tcp) in saline media. Below their Tcp, they showed the ability of keeping constant viscosity or even slight increase it, which was interpreted in terms of intermolecular hydrophobic associations. [ABSTRACT FROM AUTHOR]

Background/Aims: The present study investigated whether the transient receptor potential melastatin 4 (TRPM4) channel plays a role in high salt diet (HSD)-induced endothelial injuries. Methods: Western blotting and immunofluorescence were used to examine TRPM4 expression in the mesenteric endothelium of Dahl salt-sensitive (SS) rats fed a HSD. The MTT, TUNEL, and transwell assays were used to evaluate the cell viability, cell apoptosis, and cell migration, respectively, of human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were used to determine the concentrations of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), and E-selectin. Carboxy- H2DCFDA, a membrane-permeable reactive oxygen species (ROS)-sensitive fluorescent probe, was used to detect intracellular ROS levels. Results: TRPM4 was mainly expressed near the plasma membrane of mesenteric artery endothelial cells, and its expression level increased in SS hypertensive rats fed a HSD. Its protein expression was significantly upregulated upon treatment with exogenous hydrogen peroxide (H2O2) and aldosterone in cultured HUVECs. Cell viability decreased upon treatment with both agents in a concentration-dependent manner, which could be partially reversed by 9-phenanthrol, a specific TRPM4 inhibitor. Exogenous H2O2 induced apoptosis, enhanced cell migration, and increased the release of adhesion molecules, including ICAM-1, VCAM-1, and E-selectin, all of which were significantly attenuated upon treatment with 9-phenanthrol. Aldosterone and H2O2 induced the accumulation of intracellular ROS, which was significantly inhibited by 9-phenanthrol, suggesting that oxidative stress is one of the mechanisms underlying aldosterone-induced endothelial injury. Conclusions: Given the fact that oxidative stress and high levels of circulating aldosterone are present in hypertensive patients, we suggest that the upregulation of TRPM4 in the vascular endothelium may be involved in endothelial injuries caused by these stimuli. [ABSTRACT FROM AUTHOR]

Purpose: To identify the differences in genotype frequencies of salt-sensitive genes between residents of fishing communities (FCs) and nonfishing communities (NFCs). Methods: The subjects included 18,156 individuals (8,043 males [44%] and 10,113 females [56%]; average age: 57.2±16.1 years) from the general population who were registered with large-scale genome banks and resided in 30 prefectures and 78 different regions in Japan. The measurement items were age, sex, blood pressure, presence or absence of hypertension, body mass index, alcohol consumption, and smoking habit. Furthermore, to analyze the genotype frequencies of salt-sensitive genes, α-adducin 1 (ADD1), angiotensinogen (AGT), angiotensin II receptor type 1 (AT1), and guanine nucleotide-binding protein β peptide 3 (GNB3) were measured. According to the 2004 government classification of municipalities (cities, towns, and villages), communities existing in areas bordering an ocean and with an ocean port were defined as FCs (28 areas). The others were defined as NFCs (50 areas). A logistic regression model was used for comparison of genotype frequencies between subjects residing in FCs and NFCs. Results: Of the included subjects, 4,916 (27.0%) and 13,240 (73.0%) resided in FCs and NFCs, respectively. In FCs, the mean age was 59.4±16.7 years and men accounted for 41.0% of the cohort (n=2,015). In NFCs, the mean age was 56.4±15.8 years and men accounted for 45.5% of the cohort (n=6,028). The adjusted odds ratios of the AA and AG genotypes compared with the GG genotype for AGT were 0.80 (95% confidence interval [CI]: 0.68-0.95) and 0.76 (95% CI: 0.64-0.91), respectively. The adjusted odds ratio of the CC genotype compared with AA FORAT1 was 0.63 (95% CI: 0.40-0.93). Conclusion: The incidence of the salt-sensitive genotypes AGT and AT1 in residents of FCs were significantly lower than in NFCs. [ABSTRACT FROM AUTHOR]

BACKGROUND Hypercalciuria is a frequent characteristic of hypertension. In this report we extend our earlier studies investigating the role of renal interstitial fluid calcium (ISFCa)2+ as a link between urinary calcium excretion and blood pressure in the Dahl salt-sensitive (DS) hypertensive model. METHODS Dahl salt-sensitive and salt-resistant (DR) rats were placed on control (0.45%) and high (8%) salt diets to determine if changes in renal cortical and medullary ISFCa 2+correlated with changes in urinary calcium excretion and blood pressure. RESULTS We observed that renal ISFCa 2+ was predicted by urinary calcium excretion (P < 0.05) in DS rats but not DR rats. Renal cortical ISFCa 2+ was negatively associated with blood pressure (P < 0.03) while renal medullary ISFCa 2+ was positively associated with blood pressure in DS rats (P < 0.04). In contrast, neither urinary calcium excretion nor renal ISFCa 2+ was associated with blood pressure in the DR rats under the conditions of this study. CONCLUSION We interpret these findings to suggest that decreased renal cortical ISFCa 2+ plays a role in the increase in blood pressure following a high salt diet in salt hypertension perhaps by mediating renal vasoconstriction; the role of medullary calcium remains to be fully understood. Further studies are needed to determine the mechanism of the altered renal ISFCa 2+ and its role in blood pressure regulation. [ABSTRACT FROM AUTHOR]

Introduction: Salinity is a complex environmental stress that affects the growth and production of rice worldwide. But there are some rice landraces in coastal regions that can survive in presence of highly saline conditions. An understanding of the molecular attributes contributing to the salinity tolerance of these genotypes is important for developing salt-tolerant high yielding modern genotypes to ensure food security. Therefore, we investigated the role and functional differences of two K + salt-responsive transporters. These are OsTPKa or Vacuolar two-pore potassium channel and OsHAK&#95;like or a hypothetical protein of the HAK family. These transporters were selected from previously identified QTLs from the tolerant rice landrace genotype (Horkuch) and sensitive genotype (IR29)., Methods: In silico comparative sequence analysis of the promoter sequences of two these genes between Horkuch and IR29 was done. Real-Time expression of the selected genes in leaves and roots of IR29 (salt-sensitive), I-14 and I-71 (Recombinant Inbred Lines of IR29(♀)× Horkuch), Horkuch and Pokkali (salt-tolerant) under salt-stress at different time points was analyzed. For further insight, OsTPKa and OsHAK&#95;like were chosen for loss-of-function genomic analysis in Horkuch using the CRISPR/Cas9 tool. Furthermore, OsTPKa was chosen for cloning into a sensitive variety by Gateway technology to observe the effect of gain-of-function., Results: The promoter sequences of the OsTPKa and OsHAK&#95;like genes showed some significant differences in promoter sequences which may give a survival advantage to Horkuch under salt-stress. These two genes were also found to be overexpressed in tolerant varieties (Horkuch and Pokkali). Moreover, a coordinated expression pattern between these two genes was observed in tolerant Horkuch under salt-stress. Independently transformed plants where the expression of these genes was significantly lowered, performed poorly in physiological tests for salinity tolerance. On the other hand, positively transformed T 0 plants with the OsTPKa gene from Horkuch consistently showed growth advantage under both control and salt stress., Discussion: The poor performance of the transgenic plants with the down-regulated genes OsTPKa and OsHAK&#95;like under salt stress supports the assumption that OsTPKa and OsHAK&#95;like play important roles in defending the rice landrace Horkuch against salt stress, minimizing salt injury, and maintaining plant growth. Moreover, the growth advantage provided by overexpression of the vacuolar OsTPKa K + transporter, particularly under salt stress reconfirms its important role in providing salt tolerance. The QTL locus from Horkuch containing these two transporters maybe bred into commercial rice to produce high-yielding salt tolerant rice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Haque, Elias, Jahan and Seraj.)

Well-defined stimulus-responsive polymer gels were prepared from poly(2-vinyl-4,4-dimethylazlatone) (PVDMA) via one-pot post-polymerization modification. VDMA homopolymers were reacted with diamine crosslinking agents and functional 1° or 2° amines to form polymer gels that swelled in organic solvents and, in many cases, aqueous solutions. A series of functional amine reagents, including N,N -dimethylethylenediamine (DMEDA), N,N -diethylethylenediamine (DEEDA), morpholine, 3-morpholinopropylamine (MPPA) and tetrahydrofurfurylamine (THFA), were chosen as functional amines to produce polymer gels containing environmentally sensitive species. 13 C solid-state NMR and FTIR spectroscopic measurements confirmed complete conversion of the reactive scaffolds. pH-dependent swelling behavior at ambient temperature was observed in DMEDA-, DEEDA- and MPPA-modified hydrogels. Kinetic studies showed the swelling behaviors of DMEDA-modified hydrogels were regulated by cross-linker type and concentration in acidic water (pH = 4) at ambient temperature. The swelling ratio of hydrogels modified by DEEDA, MPPA and THFA also depended strongly on temperature, indicating successful synthesis of thermoresponsive gels. Furthermore, the concentration of added sodium sulfate played a significant role with respect to the swelling properties of MPPA-modified hydrogels. These smart materials may be of interest in the biomedical field as well as in other applications. [ABSTRACT FROM AUTHOR]

Excess dietary salt intake is a major contributing factor to the pathogenesis of salt-sensitive hypertension. Strong evidence suggests that salt-sensitive hypertension is attributed to renal dysfunction, vascular abnormalities, and activation of the sympathetic nervous system. Indeed, sympathetic nerve transections or interruption of neurotransmission in various brain centers lowers arterial blood pressure (ABP) in many salt-sensitive models. The purpose of this article is to discuss recent evidence that supports a role of plasma or cerebrospinal fluid hypernatremia as a key mediator of sympathoexcitation and elevated ABP. Both experimental and clinical studies using time-controlled sampling have documented that a diet high in salt increases plasma and cerebrospinal fluid sodium concentration. To the extent it has been tested, acute and chronic elevations in sodium concentration activates the sympathetic nervous system in animals and humans. A further understanding of how the central nervous system detects changes in plasma or cerebrospinal fluid sodium concentration may lead to new therapeutic treatment strategies in salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To investigate microRNAs (miRNAs) in urinary exosomes and their association with an individual's blood pressure response to dietary salt intake. Design and methods: Human urinary exosomal miRNome was examined by microarray. Results: Of 1898 probes tested, 194 miRNAs were found in all subjects tested. 45 miRNAs had significant associations with salt sensitivity or inverse salt sensitivity. Conclusion: The expression of 45 urinary exosomal miRNAs associates with an individual's blood pressure response to sodium. [Copyright &y& Elsevier]

20-HETE (20-hydroxyeicosatetraenoic acid), a vasoconstrictor metabolite of arachidonic acid formed through the action of CYP4A (cytochrome P450-4A) in vascular smooth muscle cells, has been implicated in the development of hypertension and vascular dysfunction. There have been a number of reports in human subjects demonstrating an association between elevated urinary excretion of 20-HETE and hypertension, as well as increased 20-HETE production and vascular dysfunction. The Dahl SS (salt-sensitive) rat is a genetic model of salt-sensitive hypertension that exhibits vascular dysfunction, even when maintained on a normal-salt diet and before the development of hypertension. This mini-review highlights our current research on the role of CYP4A and 20-HETE in the vascular dysfunction of the Dahl SS rat. In our studies, the SS rat is compared with the consomic SS-5BN rat, having chromosome 5 from the salt-resistant Brown Norway rat (carrying all CYP4A genes) introgressed on to the SS genetic background. Our laboratory has demonstrated restoration of normal vascular function in the SS rat with inhibition of the CYP4A/20-HETE pathway, suggesting a direct role for this pathway in the vascular dysfunction in this animal model. Our studies have also shown that the SS rat has an up-regulated CYP4A/20-HETE pathway within their cerebral vasculature compared with the SS-5BN consomic rat, which causes endothelial dysfunction through the production of ROS (reactive oxygen species). Our data shows that ROS influences the expression of the CYP4A/20-HETE pathway in the SS rat in a feed-forward mechanism whereby elevated ROS stimulates production of 20-HETE. The presence of this vicious cycle offers a possible explanation for the spiralling effects of elevated 20-HETE on the development of vascular dysfunction in this animal model. [ABSTRACT FROM AUTHOR]

The article presents a study on the correlates of insulin resistance in nondiabetic salt-resistant (SR) and salt-sensitive (SS) subjects. It notes that salt-sensitivity of blood pressure (SSBP) is characterized by changes in systemic arterial pressure that parallel changes in sodium balance. It adds that SR is marked by the excretion of sodium load without blood pressure (BP) changes. Findings show that SS subjects have a lower insulin sensitivity index as compared to the SR group.

The responses of sympathetic nerve activity to transient stress can be exaggerated in salt-sensitive (SS), hypertensive subjects. Cardiac and renal interstitial norepinephrine (iNE) levels during and after transient hypercapnia were investigated in conscious SS rats. Dahl SS and salt-resistant (SR) 6-wk-old rats were fed a high-salt diet, and at 12 wk iNE levels in the heart and kidney were determined using microdialysis with probes inserted in the left ventricular (LV) wall and kidney. A telemetry system determined blood pressure and heart rate (HR) in separate animals. After recovery from the operation, data were collected before, during, and after exposure to normoxic 10% CO2 for 25 min under unanesthetized conditions. The plasma NE concentrations at baseline did not differ between the two strains. Both cardiac and renal iNE levels were much higher in SS rats than in SR rats at baseline as well as during hypercapnic stress. After stress, the markedly increased iNE levels of SS rats were prolonged in the LV as well as in the kidney. During hypercapnic stress, HR decreased in both SS and SR rats, while sudden increases in HR immediately after the withdrawal from stress were followed by its slower reduction in SS rats compared with SR rats. In conclusion, transient hypercapnic stress causes exaggerated and prolonged elevation of iNE levels in the heart as well as in kidneys of SS animals. [ABSTRACT FROM AUTHOR]

Large-conductance Ca2+-activated K+ (BK) channels are composed of pore-forming α-subunits and accessory β1-subunits that modulate Ca2+ sensitivity. BK channels regulate arterial myogenic tone and renal Na+ clearance/K+ reabsorption. Previous studies using indirect or short-term blood pressure measurements found that BK channel β1-subunit knockout (BK β1-KO) mice were hypertensive. We evaluated 24-h mean arterial pressure (MAP) and heart rate in BK β1-KO mice using radiotelemetry. BK β1-KO mice did not have a higher 24-h average MAP when compared with wild-type (WT) mice, although MAP was ~10 mmHg higher at night. The dose-dependent peak declines in MAP by nifedipine were only slightly larger in BK β1-KO mice. In BK β1-KO mice, giving 1% NaCl to mice to drink for 7 days caused a transient (5 days) elevation of MAP (~5 mmHg); MAP returned to pre-saline levels by day 6. BK β1-KO mesenteric arteries in vitro demonstrated diminished contractile responses to paxilline, increased reactivity to Bay K 8644 and norepinephrine (NE), and maintained relaxation to isoproterenol. Paxilline and Bay K 8644 did not constrict WT or BK β1-KO mesenteric veins (MV). BK β1-subunits are not expressed in MV. The results indicate that BK β1-KO mice are not hypertensive on normal or high-salt intake. BK channel deficiency increases arterial reactivity to NE and L-type Ca2+ channel function in vitro, but the L-type Ca2+ channel modulation of MAP is not altered in BK β1-KO mice. BK and L-type Ca2+ channels do not modulate murine venous tone. It appears that selective loss of BK channel function in arteries only is not sufficient to cause sustained hypertension. [ABSTRACT FROM AUTHOR]

Cellulose hydrogels with quaternary ammonium (QA) groups were prepared via the etherification and cross-linking reaction. The structure of the functional hydrogels with QA groups was confirmed with FT-IR. Differential scanning calorimeter (DSC) analysis indicated that there was a large amount of free water in the hydrogels. The hydrogels showed salt-sensitivity behavior, and they also exhibited a strong antibacterial activity toward Escherichia coli. [ABSTRACT FROM AUTHOR]

1. In spontaneously hypertensive rats (SHR), the contributions of the baroreflex and central autonomic commands to the control of heart period (HP) vary among wake–sleep states and are impaired during quiet wakefulness and rapid eye movement sleep (REMS), respectively. 2. Dahl salt-sensitive (SS) rats are genetically susceptible to salt-sensitive hypertension, the development of which depends on diet. Substitution of chromosome 13 of SS rats with that of Brown Norway rats confers salt-resistance to consomic SS-13BN rats. 3. In the present study, we tested whether differences in the central and baroreflex contributions to HP control occur among wake–sleep states in SS and SS-13BN rats and reflect genetic susceptibility to hypertension. Rats ( n = 5 per group) were fed a prohypertensive diet late during development to minimize hypertension in SS rats and were instrumented with an arterial catheter and electrodes for discriminating wake–sleep states. 4. The cross-correlation function between HP and blood pressure indicated that, in SS and SS-13BN rats, the contributions of the baroreflex and central commands to the control of HP differed significantly among wake–sleep states, with central commands outweighing the baroreflex in REMS. However, these contributions did not differ significantly between SS and SS-13BN rats in any wake–sleep state. 5. The data suggest that differences in the central and baroreflex contributions to HP control among wake–sleep states, which have been demonstrated in SHR, can be generalized to other rat models used in hypertension research. Impairments in the baroreflex and central autonomic control of HP during quiet wakefulness and REMS, respectively, cannot be generalized as an index of genetic susceptibility to hypertension. [ABSTRACT FROM AUTHOR]

Abstract: It is known that renal nitric oxide (NO) is an important controller of urinary sodium excretion. A defect in the kidney''s NO system could cause salt-sensitive hypertension. Since it has been demonstrated that doxorubicin binds to the reductase domain of endothelial NO synthase (eNOS) and generates superoxide in vitro, we tested our hypothesis that a high-sodium diet would upregulate the expression of eNOS and enhance oxidative stress in the kidney of doxorubicin-treated rats, resulting in a facilitation of hypertension. At 4 weeks after treatment with doxorubicin in Sprague–Dawley rats, the systolic blood pressure significantly increased only in the high-sodium diet group. The expressions of eNOS protein in the renal cortex and medulla were significantly higher in high-sodium groups than in normal-sodium groups, regardless of doxorubicin treatment. In rats treated with doxorubicin, a biomarker of oxidative damage 8-hydroxy-2′-deoxyguanosine (8-OHdG) immunohistological staining of renal tissues showed strong staining of the proximal and distal tubules. In particular, rats with doxorubicin in the high-sodium diet group demonstrated a significant increase in urinary exertion of 8-OHdG as well as more prominently stained tubules against 8-OHdG antibody, but markedly lower urinary NO x excretion than in rats without doxorubicin, even than in the untreated, low-sodium group. In conclusion, these results indicate that the oxidative stress induced by doxorubicin impairs NO production in the kidney. As such, doxorubicin treatment appears to contribute to the development of salt-sensitive hypertension through reductive activation of upregulated eNOS by a high-sodium diet instead of NO production. [Copyright &y& Elsevier]

Salinity is at present one of the most serious environmental problems influencing crop growth. It has been extensively demonstrated that salinity affects several physiological processes in the plant, including the plant–water relations of most salt-sensitive crops species. In this study, the effects of salinity on the plant–water relations of kidney bean (Phaseolus vulgaris L.) and the possibility that foliarly applied glycinebetaine improves these water relations are examined. Kidney bean plants were grown in a greenhouse and treated with 0, 30, 50 and 100 mM NaCl, combined with 0, 10 and 30 mM glycinebetaine in foliar applications. Increased salinity levels decreased stomatal conductance, photosynthetic rate, transpiration and leaf relative water content in the 30, 50 and 100 mM treatments relative to the control treatment. Glycinebetaine applications of 10 mM increased stomatal conductance at 50 mM NaCl, ameliorating significantly the effect of salinity on water relations through increases in the leaf relative water content. At 100 mM NaCl, 30 mM glycinebetaine applications in particular contributed to osmotic stress, and had an adverse effect on plants. Our experiment suggests that glycinebetaine can be used as an alternative treatment to reduce the effects of salt stress on the water relations of salt-sensitive plants, but only to limited salinity levels. Furthermore, the improvement in the water status of kidney beans was dose dependent, suggesting that the concentration of glycinebetaine essential for the survival of salt-sensitive plants is species specific and must be determined individually for each plant species. [ABSTRACT FROM AUTHOR]

Hypertension is the most prevalent clinical symptom arising from various cardiovascular disorders. Likewise, it is considered a precursor or sequelae to the development of acute coronary artery disease and congestive heath failure (CHF). Hypertension has been considered a cardinal criterion to determine cardiovascular function. According to the World Health Organization (WHO) global observatory data, hypertension causes more than 7.5 million deaths a year, about 12.8% of the total human mortality. Similarly, the Center for Disease Control (CDC) states that 35% of the American adults have been estimated to have a persistently high blood pressure, which makes it about one in every three adults. Hypertension is a modifiable symptom that can be managed through pharmacological and non-pharmacological methods and standard protocols set forth by the American Heart Association (AHA). With new findings from various clinical trials related to the management of hypertension, new developments and recommendations have been made to update the previously established protocols for hypertension. This article aims to discuss and dissect the modern updates of hypertension management as comprehensively elaborated in the 2017 Hypertension Clinical Practice Guidelines., Competing Interests: The authors have declared that no competing interests exist.