Mechanism of trehalose-enhanced metabolism of heterotrophic nitrification-aerobic denitrification community under high-salt stress / 生物工程学报

Heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria are aerobic microorganisms that can remove nitrogen under high-salt conditions, but their performance in practical applications are not satisfactory. As a compatible solute, trehalose helps microorganisms to cope with high salt stress by participating in the regulation of cellular osmotic pressure, and plays an important role in promoting the nitrogen removal efficiency of microbial populations in the high-salt environment. We investigated the mechanism of exogenous-trehalose-enhanced metabolism of HN-AD community under high-salt stress by starting up a membrane aerobic biofilm reactor (MABR) to enrich HN-AD bacteria, and designed a C150 experimental group with 150 μmol/L trehalose addition and a C0 control group without trehalose. The reactor performance and the community structure showed that NH4+-N, total nitrogen (TN) and chemical oxygen demand (COD) removal efficiency were increased by 29.7%, 28.0% and 29.1%, respectively. The total relative abundance of salt-tolerant HN-AD bacteria (with Acinetobacter and Pseudofulvimonas as the dominant genus) in the C150 group reached 66.8%, an 18.2% increase compared with that of the C0 group. This demonstrated that trehalose addition promoted the enrichment of salt-tolerant HN-AD bacteria in the high-salt environment to enhance the nitrogen removal performance of the system. In-depth metabolomics analysis showed that the exogenous trehalose was utilized by microorganisms to improve proline synthesis to increase resistance to high-salt stress. By regulating the activity of cell proliferation signaling pathways (cGMP-PKG, PI3K-Akt), phospholipid metabolism pathway and aminoacyl-tRNA synthesis pathway, the abundances of phosphoethanolamine, which was one of the glycerophospholipid metabolites, and purine and pyrimidine were up-regulated to stimulate bacterial aggregation and cell proliferation to promote the growth of HN-AD bacteria in the high-salt environment. Meanwhile, the addition of trehalose accelerated the tricarboxylic acid (TCA) cycle, which might provide more electron donors and energy to the carbon and nitrogen metabolisms of HN-AD bacteria and promote the nitrogen removal performance of the system. These results may facilitate using HN-AD bacteria in the treatment of high-salt and high-nitrogen wastewater.

Relationship between the intake of salt and salted food and the infection of Helicobacter pylori in 40-69 years old local residents in a county with high gastric cancer risk in Anhui Province / 中华疾病控制杂志

Objective The aim of the present study was to investigate the relationship between the intake of salt and salted food and the infection of Helicobacter pylori (Hp) among 40-69 years old local residents in a county with high gastric cancer risk in Anhui province. Methods From July 2015 to August 2018, we conducted a questionnaire and a serological test for Hp among 40-69 years old local residents in Lujiang county, Anhui province. The questionnaire focused on the consumptions of salt and salted food. The relationship between Hp infection and risk factors was analyzed by gender. Univariate and multivariate logistic regression analysis were used to analyze the relevant influencing factors. Results The Hp infection rate of total local residents was 50.07%. Among male subjects, age, body mass index(BMI), marital status, educational level, job, labor intensity and income had no link to Hp infection (all P>0.05). But among female subjects, BMI was associated with Hp infection ( 2=13.454,P=0.001). Besides, alcohol consumption was a risk factor for Hp infection in male subjects(OR=1.789，95% CI:1.188-2.694，P=0.003). But, high intake of salt and salted food had no effect on Hp infection after adjustment for alcohol consumption variable in men using multivariate analysis (all P>0.05). After adjusted for BMI variable among female individuals, high salt intake (≥9 g/day) (OR=1.462，95% CI:1.060-2.015，P=0.021) and the high salted food intake (≥1 times /day) were risk factors for Hp infection in women(OR=1.560，95% CI:1.021-2.383，P=0.040). Conclusions In one county with high gastric cancer risk in Anhui province, high salt intake (≥9 g/day) and high salted food intake (≥1 times/day) are risk factors for Hp infection among 40-69 years old female local residents.

High-salt exposure induces macrophage polarization to promote proliferation and phenotypic transformation of co-cultured renal fibroblasts / 南方医科大学学报

OBJECTIVE@#To investigate high-salt exposure-induced polarization of mononuclear macrophages and the changes in proliferation and phenotypic transformation of renal fibroblasts in a co-culture system.@*METHODS@#Cultured mononuclear macrophages were exposed to high salt (161 mmol/L Na +) for 2 h and the surface markers of M0, M1 and M2-type macrophages were detected with RT-qPCR. The culture medium of the macrophages in normal and high-salt groups was collected for detection of the mRNA and protein levels of IL-6 and TGF-β1 using RT-qPCR and ELISA. A co-culture system of high salt-exposed macrophages and renal fibroblasts (NRK-49F) was established using a Transwell chamber, and the changes in proliferation and migration of NRK-49F cells were examined using EdU assay and Transwell assay, respectively. Western blotting was performed to detect the expressions of collagen I, collagen III and collagen α-SMA in NRK-49F cells.@*RESULTS@#The high salt-exposed macrophages showed significantly increased mRNA levels of M2-type macrophage surface markers mannose receptor and arginase (@*CONCLUSIONS@#High-salt exposure induces polarization of mononuclear macrophages into M2-type macrophages and promotes secretion of IL-6 and TGF-β1 by the macrophages to induce the proliferation and phenotypic transformation of NRK-49F cells.

Blockade of Endogenous Angiotensin-(1-7) in Hypothalamic Paraventricular Nucleus Attenuates High Salt-Induced Sympathoexcitation and Hypertension / 神经科学通报·英文版

Angiotensin (Ang)-(1-7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1-7) in the hypothalamic paraventricular nucleus (PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines (PICs) and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt (8% NaCl) or a normal salt diet (0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1-7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma norepinephrine (NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 expression and superoxide production in the PVN. Microinjection of A-779 (3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1-7) in the PVN, through modulation of PICs and oxidative stress.

Effect of high salt diet on arterial blood pressure in urea transporter B gene depletion mice and its mechanism / 吉林大学学报(医学版)

Objective: To investigate the effect of high salt diet on the arterial blood pressure in the urea transporter B (UT-B) gene depletion (UT-B-/-) mice, and to clarify the possible mechanism of the UT-B-/- leading to the changes in the arterial blood pressure of the mice. Methods: The heterozygous (UT-B/-) mice were mated to obtain the wild-type (UT-B1/) and UT-B-/- mice with the same genetic background. The 4-week-old male UT-B1/1 and UT-B-/- mice were selected and fed on normal diet (0. 3% NaCl) or high salt diet (8. 0% NaCl) for 4 weeks. The mice were divided into UT-B/1 mice + normal diet (UT-B /1 +N) group, UT-B-/- mice + normal diet (UT-B-/- +N) group, UT-B1/1 mice+high salt diet (UT-B /1 +H) group, and UT-B-/- mice + high salt diet (UT-B-/- +H) group. The changes in water intakes and mean arterial pressures of the mice in various groups were monitored; RT-PCR, Western blotting and immunohistochemistry were used to detect the expression levels and location of UT-B mRNA and protein in choroid plexus (CP) of the brain tissue of the mice. The levels of serum angiotensin II (Ang II) and the Na levels in cerebrospinal fluid of the mice in various groups were determined by ELISA. Results: The PCR results of genomic DNA of mouse tail showed that there was a 400 bp base fragment in the UT-B mice, 250 and 400 bp base fragments in the UT-B mice, and 250 bp base fragment in the UT-B- - mice. Compared with normal salt diet group, the water intake of the mice in high salt diet was significantly increased (P<0. 01); compared with UT-B-/- +N group and UT-B1/1 + H group, the mean arterial pressure of the mice in UT-B-/- +H group was significantly increased (P<0. 01). The UT-B mRNA and protein expressed in the epithelial cells of CP in the UT-B/1 mice. Compared with UT-B-/- +N group and UTS1/ mice+H group, the Ang II level in serum of the mice in UT-B-/- mice+H group was significantly increased (P< 0.01); the Na level in cerebrospinal fluid of the mice was significantly increased (P< 0. 05). Conclusion: High salt diet can cause a significant increase in the mean arterial pressure in the UT-B-/- mice, and its mechanism is related to increasing the serum Ang II level and the Na' level in cerebrospinal fluid in the mice.

Effect of high salt diet on the renal medullary cyclooxygenase 2 expression / 中华肾脏病杂志

Objective To examine the effect and mechanism of high salt diet on the renal medullary cyclooxygenase 2 (COX2) expression and urinary sodium excretion. Methods Thirty male C57BL/6j mice were divided into four groups: (1) normal salt diet group (0.4％NaCl, n=5); (2) high salt diet group (8％NaCl, n=5);(3) Bortezomib+normal salt diet group (n=10);(4) Bortezomib+high salt diet group (n=10). The different groups were pre-treated with saline or bortezomib ,followed by normal salt diet or high salt diet for three days. All the mice were maintained on metabolic cage at the last day and allowed free access to water. Twenty-four hours urine was collected. Body weight, urine volumes were documented. At the end of experiments, mice were sacrificed under anesthesia and the kidneys were harvested for Western blotting and immunohistochemistry. The transgenic mice carrying a luciferase reporter driven by an NF-κB response promoter, HIV long terminal repeat (LTR) (HLL mice) were used to explore the effect of high salt diet on renal medullary NF-κB activity. HLL mice were fed with normal salt diet or high salt diet for 3 days, after which renal medullary luciferase activity was determined using a commercial luciferase assay kit. Luciferase activity was quantified with a luminometer and adjusted for the total amount of proteins. The cellular location of NF-κB was examined using immunohistochemistry of NF-κB p65 staining. Results (1) Western blotting results showed high salt diet significantly increased the COX2 expression in the renal medulla of C57BL/6j mice (P﹤0.05). (2) High salt diet significantly increased NF-κB luciferase reporter activity in the HLL mice renal medullary tissues when compared to normal salt diet (P﹤0.05). The immunohistochemistry of NF-κB p65 showed the expression of NF-κB was mainly in the renal interstitial cells. (3) Western blotting results showed bortezomib inhibited the renal medullar COX2 expression induced by high salt diet (P﹤0.05). (4) Bortezomib decreased the urinary sodium excretion of high salt diet mice (P﹤0.05), but had no change on urine volume. Conclusions High salt diet induce renal medullary COX2 over-expression and activate the activation of NF-κB in renal medullary. Bortezmoib can inhibit the renal medullar COX2 expression induced by high salt diet. The NF-κB pathway activation may involve in the regulation of renal medullar COX2 expression by high salt diet.

High salt inhibits nitric oxide production in thoracic aortic endothelial cells and its mechanism / 中国药理学通报

Aim To investigate the effect of high-salt model of mouse thoracic aortic endothelial cells on the production of nitric oxide (NO) . Methods After preincubation of thoracic aortic endothelial cells with transient receptor potential vanilloid 4 (TRPV4) inhibitor HC067047, the effects of TRPV4 on NO production were studied by Ca2+and NO staining with calcium ion fluorescent probe Fluo-4 and NO fluorescent probe DAF-FM DA. The thoracic aortic endothelial cells were stimulated with a high salt concentration of 60 mmo! L"1 to detect Ca2+influx and NO production Compared with control group, suppression of TRPV4 inhibited Ca2+influx and NO production in thoracic aortic endothelial cells, and high salt conditions inhibited TRPV4-medicated Ca2+influx and NO production compared with mannitol under the same osmotic pressure. Conclusion In high salt state, the inhibition of TRPV4 channel leads to the decrease of Ca2+influx and the down-regulation of NO synthesis.

The inhibitory effect of α-lipoic acid on the high salt-induced hypertension rats / 重庆医学

Objective To investigate whether the excessive production of reactive oxygen species (ROS) in the mitochondria of the rostral ventrolateral medulla (RVLM) can inhibit the high salt-induced hypertension response.Methods A total off 32 male rats were divided into two groups:two groups were given normal salt diet (0.3％ NaCl) for 8 weeks (n=16) and high salt diet (8％ NaCl) for 8 weeks (n=16,induced hypertension model) respectively.The two groups were divided into four groups,two groups were given α-lipoic dissolving in 0.9％ normal saline (60 mg/kg),two groups were fed with saline for 9 weeks.There were ffour groups:the experimental group (n=8,the hypertension model sample fed α-lipoic acid),the model group (n=8,the hypertension model sample fed saline),the control group (n=8,normal salt diet sample fed α-lipoic acid) and the blank control group (n=8,normal salt diet sample ffed saline).Monitored the change of the arterial pressure and detected the expression off superoxide by immunofluorescence at the end of the experiment,measured the expression of NAD(P)H NOX2,NOX4 and Cu/Zn-SOD in RVLM by Western blot;determined the expression differences of oxidative stress related substances such as mitochondrial malondialdehyde(MDA)in RVLM by ELISA.Results The mean arterial pressure (MAP) in the experimental group was lower than that in the model group,the difference was statistically significant (P＜0.05);in the experimental group and the model group the intensities of fluorescent-labled dihydroethidium(DHE) were 60.2±3.1,99.1±3.8;the numbers of positive neurons in Cu/Zn-SOD were 20.8±1.1,6.9 ± 1.2;the numbers of NOX2 positive neurons were 12.3 ± 3.5,25.1 ±5.4;the numbers of NOX4 positive neurons were 10.1±2.2,13.3±4.1,the difference was statistically significant (P＜0.05).Western blot showed that the NOX2 levels of the experimental group and the model group were 78.9 ± 2.0,112.7 ± 3.8;the levels of NOX4 were 63.2± 2.1,99.4 ± 1.7.The levels of Cu/Zn-SOD in RVLM of the experimental group and the model group were 19.7 ±1.6,10.3± 1.2,the difference was statistically significant (P＜0.05);the levels of mitochondrial superoxide dismutase (SOD) were (33.1±3.8),(15.2±1.7)U/mg,the difference was statistically significant (P＜0.05).The levels of mitochondrial glutathione (GSH) in the experimental group and the model group were (5.2±0.9),(2.3±0.5)μmol/g;the levels of norepinephrine (NE) were (325.8 ± 7.3),(467.9 ± 6.1) pg/mL,the difference was statistically significant (P＜0.05).Conclusion α-lipoic acid could decrease the expression of NOX2,NOX4 and the bioenergy of mitochondria enzyme,and increase the intracellular antioxidant ability in the RVLM during the development of hypertension to inhibit the oxidative stress response in the development of hypertension.

Selection of suitable reference genes for abiotic stress-responsive gene expression studies in peanut by real-time quantitative PCR

Background: Because of its strong specificity and high accuracy, real-time quantitative PCR (RT-qPCR) has been a widely used method to study the expression of genes responsive to stress. It is crucial to have a suitable set of reference genes to normalize target gene expression in peanut under different conditions using RT-qPCR. In this study, 11 candidate reference genes were selected and examined under abiotic stresses (drought, salt, heavy metal, and low temperature) and hormone (SA and ABA) conditions as well as across different organ types. Three statistical algorithms (geNorm, NormFinder and BestKeeper) were used to evaluate the expression stabilities of reference genes, and the comprehensive rankings of gene stability were generated. Results: The results indicated that ELF1B and YLS8 were the most stable reference genes under PEG-simulated drought treatment. For high-salt treatment using NaCl, YLS8 and GAPDH were the most stable genes. Under CdCl2 treatment, UBI1 and YLS8 were suitable as stable reference genes. UBI1, ADH3, and ACTIN11 were sufficient for gene expression normalization in low-temperature experiment. All the 11 candidate reference genes showed relatively high stability under hormone treatments. For organs subset, UBI1, GAPDH, and ELF1B showed the maximum stability. UBI1 and ADH3 were the top two genes that could be used reliably in all the stress conditions assessed. Furthermore, the necessity of the reference genes screened was further confirmed by the expression pattern of AnnAhs. Conclusions: The results perfect the selection of stable reference genes for future gene expression studies in peanut and provide a list of reference genes that may be used in the future.

Effect of response to phenylephrine-mediatedsignal pathway in renal arteries of offspring rats inducedby maternal high-salt diet / 中国药理学通报

Aim To study the effect of high salt diet during pregnancy on the development of renal vessels in offspring rats and its mechanism.Methods Natural pregnant Sprague-Dawley rats were randomly divided into high-salt group and control group.The pregnant rats in the high-salt group were given high-salt diet of 8% NaCl content , while the control group normal diet with 1% NaCl content.In both groups, pregnant rats were given normal drinking water.After delivery, all mothers returned to normal diet and all neonatal rats were breast-fed until one month old.The adult male off springs were used as experimental animals.The vessel tone of renal interlobar arteries and electrophysiological behavior of single vascular smooth muscle cells (VSMCs) were detected respectively.Results The contractile response of renal arteries to phenylephrine(Phe) in high-salt group was stronger than that in the control group(P0.05).Conclusions High-salt diet during pregnancy could increase the sensitivity of renal interlobar arterial contractile response to Phe in adult male offsprings, which is associated with PKC-mediated BK channels pathway.Maternal high-salt diet during pregnancy may increase the risk of renal vascular diseases in adult offsprings.

The study on the mechanism of platelet in the development of salt-sensitive hypertension via inflammation / 中国比较医学杂志

Objective To investigate the role and mechanism of platelet in the development of salt-sensitive hypertension.Methods 25 Dahl salt-sensitive rats (Dahl SS) were divided into three groups: low-salt diet (0.12% NaCl, LS), high-salt diet (8%NaCl, HS) and high-salt diet + platelet inhibitor (8%NaCl+busulfan, HS+bus).Blood pressures were measured by tail-cuff method.After six weeks, animals were sacrificed.Platelet p-selectin expression, platelet cytosolic Ca2+ concentration, platelet-leukocyte aggregation (PLA) in peripheral blood, and immune cells infiltrated on aortic walls were assessed by flow cytometry, and serum IL-6 level was tested by ELISA in vivo.Platelets purified from SD rats were treated with normal salt (0.9%NaCl) and high salt (1.3%NaCl), then the cytosolic Ca2+ concentration and p-selectin expression of platelet were detected.Results We found that Dahl SS rats with high-salt diet, relative to low-salt diet, presented with high blood pressure and increased the ratio of platelet p-selectin expression, Ca2+ concentration.IL-6 level and PLA in peripheral blood, and the number of infiltrated immune cells on aortic walls were also significantly elevated in high-salt diet group.The whole events were ameliorated by the platelet inhibitor busulfan.Cytosolic Ca2+ concentration and p-selectin expression were also increased in purified platelets treated with high salt than those treated with low salt (P < 0.05).Conclusions Our findings suggest that high salt induced platelet activation with increased Ca2+ concentration may play an important role in the development of salt-sensitive hypertension via vascular inflammation.However, the detailed mechanisms of platelet activation and development of high blood pressure via inflammation induced by high salt intake remain to be determined.

High salt diet enhances the physical coupling between TRPV4 and cPLA2 / 中国药理学通报

Aim To observe the physical coupling between transient receptor potential channel vanilloid type 4 (TRPV4 ) and cPLA2 in endothelial cells. Methods We investigated the physical association of TRPV4-cPLA2 coupling by immunofluorescence reso-nance energy transfer (immuno-FRET)to assess the spatial proximity between TRPV4 and cPLA2 in human microvascular endothelial cells (HMEC),primary cul-tured endothelial cells and in thoracic aortas rings from high salt-induced hypertension mice.Results At the cellular level,with high salt treatment,the physical in-teraction of TRPV4 and cPLA2 was significantly en-hanced in primary vascular endothelial cells and HMEC.Furthermore, in thoracic aortas rings from high salt-induced hypertension mice,we found an in-creases interaction between TRPV4 and cPLA2 in en-dothelial cells from arterial segments .Conclusion High-salt treatment increases the endothelial TRPV4-cPLA2 coupling,indicating that this coupling may pro-vide a new target for vascular endothelial dysfunction.

Effect of caveolin-1 expression on high-salt diet-induced endothelial dys-function in type 1 diabetic rats / 中国病理生理杂志

[ ABSTRACT] AIM: To investigate the underlying mechanisms responsible for endothelial dysfunction of type 1 diabetes mellitus (DM) rats fed with high-salt diet.METHODS:Type 1 DM was induced by intraperitoneal injection of streptozotocin (70 mg/kg).Normal and diabetic rats were fed high-salt food (HS, 8% NaCl) and standard food for 6 weeks, respectively.Isometric tension of the mesenteric arteries were measured .The expression of Akt , endothelial nitric oxide synthase (eNOS) and caveolin-1 (Cav-1) was examined by Western blot .RESULTS:The rats in DM+HS group exhibited more pronounced impairment of vasorelaxation to acetylcholine and insulin compared with either DM group or HS group (P<0.01).Akt and eNOS phosphorylation levels, and nitric oxide (NO) concentration in DM +HS group were significantly lower than those in DM group (P<0.01).The level of Cav-1 in DM+HS group was significantly higher than that in DM group and HS group .CONCLUSION:Impaired endothelial Akt activation , increased Cav-1 expression and re-sultant decreased eNOS activation contribute to aggravate high-salt diet-induced endothelial dysfunction and hypertension in DM rats.

Correlations Among Threshold and Assessment for Salty Taste and High-salt Dietary Behavior by Age / 대한지역사회영양학회지

OBJECTIVES: The purpose of this study was to analyze correlation thresholds and assessment for salty taste and high-salt dietary behaviors by age. METHODS: A total of 524 subjects including 100 each of elementary school students, middle school students, college students, and elderly as well as 124 adults were surveyed for detection and recognition thresholds, salty taste assessments, and high-salt dietary behaviors. RESULTS: Elementary students had a lower detection threshold (p<0.05) and recognition threshold (p<0.01) than did the other groups. Salty taste assessments were lowest among elementary students, followed by middle school students, while college students, adults, and elderly had higher assessment score (p<0.001). Elementary students had significantly lower scores for high-salt dietary behavior than did middle school students, college students, adults and elderly (p<0.001). Middle school students had higher scores for high-salt dietary behavior than did elementary school students and elderly (p<0.001) but no meaningful difference was found in dietary behavior scores between college students, adults, and elderly. There were positive correlations between high-salt dietary behavior and detection thresholds (p<0.001), recognition thresholds (p<0.001), and salty taste assessment (p<0.001). High-salt dietary behavior was more positively correlated with salty taste assessment than detection and recognition thresholds for salty taste. CONCLUSIONS: This study suggested that salty taste assessments were positively associated with scores for the detection and recognition thresholds and high-salt dietary behavior.

Comparison of salty taste assessment, high-salt dietary attitude and high-salt dietary behavior by stage of behavior change among students in Daegu / 한국영양학회지

PURPOSE: This study was conducted for comparison of salty taste assessment, salty taste preference, high-salt dietary attitude, and high-salt dietary behavior by stages of behavior change among school-aged children and adolescents. METHODS: A total of 1,595 students (1,126 school- aged children, 469 adolescents) from 43 elementary schools and 17 middle and high schools in Daegu were tested using salty taste kits and surveyed using questionnaires on stages of behavior change, high-salt dietary attitude, and behavior. RESULTS: Adolescents showed a significantly higher result for salty taste assessment than school-aged children (p < 0.01). In salty taste assessment, the students of pre-contemplation stage (n = 498) and contemplation stage (n = 686) showed higher scores than students of action stage (n = 351) and maintenance stage (n = 60). Regarding the salty taste preference, students of maintenance stage preferred the lower two samples (0.08%, 0.16%) and students of pre-contemplation stage preferred the higher two samples (0.63%, 1.25%). High-salt dietary attitude scores and dietary behavior scores were highest for students of pre-contemplation stage and were lowest for students of maintenance stage. CONCLUSION: Salty taste assessment, high-salt dietary attitude, and high-salt dietary behavior were significantly different by stages of behavior change among school-aged children and adolescents. This study suggests the need for examination of the stages of behavior change before nutrition education for effective education.

Effects of eplerenone on expression and activity of aortic endothelial nitric oxide synthase in hypertensive rats induced by high-salt intake / 中国病理生理杂志

[ ABSTRACT] AIM:To explore the effects of eplerenone on the expression and activity of aortic endothelial nitric oxide synthase ( eNOS) in high salt-induced hypertensive rats .METHODS: Male Wistar rats (4 week old, weighting 50~60 g) were randomly divided into control group , high-salt diet group and eplerenone group .The rats in control group were fed with ordinary rodent animal diet , the rats in high-salt group and eplerenone group were exposed to 5%salt diet for 16 weeks and administrated with the same dosage of saline or eplerenone (40 mg? kg-1? d-1 ) by gavage for 4 weeks, re-spectively.Systolic blood pressure (SBP) was measured by tail-cuff every 2 weeks.The rats were sacrificed after 16 weeks and the thoracic aorta was collected .The aldosterone content in the aorta was measured by ELISA .The protein levels of mineralocorticoid receptor (MR) and eNOS were determined by Western blot.The activitie of constitutive NOS (cNOS) was measured by chemocolorimetry .The protein localization of eNOS , neuronal nitric oxide synthase ( nNOS) and MR was observed by immunohistochemistry .RESULTS: A process of 8-week high-salt diet increased SBP gradually .SBP in the rats exposure to high salt for 16 weeks was significantly higher than that in control group ( P<0.05 ) .After 4 weeks of eplerenone treatment, SBP in the rats was significantly lower than that before treatment (P<0.05).Compared with control group, the aldosterone content in the aorta were significantly increased in high-salt diet group and eplerenone group ( P<0.05), the expression level of MR also increased significantly (P<0.05).Compared with control group, both eNOS pro-tein expression (P<0.05) and cNOS activity in high-salt diet group were significantly decreased (P<0.05).The protein expression of eNOS as well as cNOS activity in aorta increased significantly in eplerenone group compared with high -salt diet group (P<0.05).CONCLUSION:Aldosterone content in aorta of high-salt-induced hypertensive rats increases signifi-cantly .Aldosterone attenuates the protein expression of eNOS and reduces the enzyme activity through the activation of min -eralocorticoid receptor .The selective mineralocorticoid receptor antagonist eplerenone enhances the protein expression of eNOS and its activity , thereby improves eNOS function .

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.

Alkaloids of Nitraria sibirica Pall. decrease hypertension and albuminuria in angiotensin II-salt hypertension / 中国天然药物

In traditional Chinese medicine, Nitraria sibirica Pall. (Nitrariaceae) is used to treat hypertension. This study determined the effects of the total alkaloids of the leaves of Nitraria sibirica (NSTA) on blood pressure and albuminuria in mice treated with angiotensin II and a high-salt diet (ANG/HS). Adult mice were divided into three groups: control; infused with angiotensin II and fed a diet containing 4% NaCl (ANG/HS; and ANG/HS plus injection of NSTA (1 mg·kg(-1)·d(-1), i.p.). After treatment of these regimens, daily water and food intake, kidney weight, blood pressure, urinary albumin excretion, renal concentrations of inflammatory markers, including soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and the expression of renal fibrosis markers were determined. Compared to the control group, the ANG/HS group had higher blood pressure and urinary albumin excretion. Treatment with NSTA in ANG/HS mice for three weeks significantly reduced blood pressure and urinary albumin excretion. ANG/HS treatment caused elevated levels of sICAM-1 and MCP-1, as well as increased fibrosis markers. Concurrent treatment with ANG/HS and NSTA attenuated the levels and expression of renal inflammatory and fibrosis markers. Treatment with NSTA effectively reduces hypertension-induced albuminuria through the reduction of renal inflammatory and fibrosis markers.

Change of the renal hydrogen sulfide system in salt-sensitive hypertensive rats / 中华实用儿科临床杂志

Objective To study the change of the renal endogenous hydrogen sulfide (H2 S) pathway in the development of salt-sensitive hypertension in Dah1 rats.Methods Sixteen male Dah1 rats,in accordance with the random number table,were randomly divided into control group and high salt group fed with diet containing 80 g/kg NaCl.After 8 weeks,24 h urine sodium,24 h urinary protein,serum creatinine and serum urea were measured.The microstructural and ultrastructural changes in kidney were observed with light microscope and electronic microscope.The serum and kidney H2S contents were determined by using sulphur-sensitive electrode method.The mRNA levels of cystathionine β-synthase(CBS),cystathionine γ-lyase(CSE) and mercaptopyruvate sulfurtransferase(MPST) in renal tissue were determined by means of real-time polymerase chain reaction(RT-PCR).The protein expressions of CBS,CSE and MPST in renal tissue were detected by using Western blot.Results Compared with control group,high salt group rats had a significant rise in blood pressure,declined renal function,damaged renal structure,segmental glomerular sclero sis,small artery wall thickening,and occlusion of the lumen.Moreover,the endogenous H2S pathway in kidney of Dah1rats with high salt diet was downregulated markedly,demonstrated by the decreased serum and kidney H2S content,the reduced renal CBS,CSE and MPST mRNA expressions and CBS protein expression of kidney tissue.Conclusion The endogenous H2S/CBS pathway is downregulated during the development of salt-sensitive hypertension in Dah1 rats.

Effect of Modified Zexie Decoction on Renal Aquaporin-2 Expression in Hypertension Rats Induced by High-Salt / 天津医药

Objective To explore the effect of modified Zexie Decoction on renal aquaporin-2 (AQP2) expression in high-salt hypertensive rat. Methods Hypertensive rats model was established by feeding rat with 8%high salt. Rats (n=50) were divided into model group, modern medicine group, traditional Chinese medicine groups of high, medium, low dose, with 10 rats in each group. The other 10 rats were fed with ordinary diet as normal group. Rats in traditional Chinese medi?cine of high, medium, low groups were given Zexie Decoction suspension of 16.2, 10.8 and 5.4 g/(kg·d) respectively;Rats in modern medicine group was given Valsartan hydrochlorothiazide 16.65 mg/(kg·d);the model group and normal group was ad?ministered with equal volume of distilled water. Animals were feed with medications at 1 mL/100 g by gavage for 4 weeks. On the 1st , 4th , 7th , 14th and, 28th day of administration, we measured SBP and collected 24 h urine. We employed immunohis?tochemistry to detect renal AQP-2 protein expression level and RT-PCR to detect renal AQP-2 mRNA transcription level. Results The rank of SBP from high to low is:model group>traditional Chinese medicine medium and low dose groups>traditional Chinese medicine high dose group and western medicine group>normal group. The rank of urine volume from high to low is:Western medicine group and traditional Chinese medicine high dose group>traditional Chinese medicine me?dium and low dose group > normal group, the difference was not statistically significant between traditional Chinese medi?cine medium and low dose group , or between western medicine group and traditional Chinese medicine high dose group. The renal AQP-2 in epithelial cells along the collecting duct wall of rats in model group show brown particles which are darker and wider distributed than those in normal group and traditional Chinese medicine of high, medium, low dose groups. RT-PCR results show that AQP-2 mRNA expression is highest in rats of model group and lowest in rats of traditional Chi?nese medicine high dose group (P<0.05). No statistical significance of AQP mRNA level was found between traditional Chi?nese medicine low group and model group (P < 0.05). Conclusion Modified Zexie Decoction can lower blood pres?sure by inhibiting the expression of AQP-2.