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Background Substantial evidence suggests that hypertension is a significant risk factor for cognitive decline. However, it is unclear whether the genetic predisposition to hypertension is also associated with cellular dysfunction that promotes neurodegeneration. Methods Changes in blood pressure were evaluated following dietary salt-loading or administration of a regular diet in Sabra Normotensive (SBN/y) and Sabra Hypertension-prone rats (SBH/y). We performed quantitative RT-PCR and immunofluorescence staining in brain cortical tissues before salt loading and 6 and 9 months after salt loading. To examine the expression of brain cortical proteins involved in the gene regulation (Histone Deacetylase-HDAC2; Histone Acetyltransferase 1-HAT1), stress response (Activating Transcription Factor 4-ATF4; Eukaryotic Initiation Factor 2- eIF2α), autophagy (Autophagy related 4A cysteine peptidase- Atg4a; light-chain 3-LC3A/B; mammalian target of rapamycin complex 1- mTORC1) and apoptosis (caspase-3). Results Prior to salt loading, SBH/y compared to SBN/y expressed a significantly higher level of cortical HAT1 (protein), Caspase-3 (mRNA/protein), LC3A, and ATF4 (mRNA), lower levels of ATG4A (mRNA/protein), LC3A/B, HDAC2 (protein), as well as a lower density of cortical neurons. Following dietary salt loading, SBH/y but not SBN/y developed high blood pressure. In hypertensive SBH/y, there was significant upregulation of cortical HAT1 (protein), Caspase-3 (protein), and eIF2α ~ P (protein) and downregulation of HDAC2 (protein) and mTORC1 (mRNA), and cortical neuronal loss. Conclusions The present findings suggest that genetic predisposition to hypertension is associated in the brain cortex with disruption in autophagy, gene regulation, an abnormal response to cellular stress, and a high level of cortical apoptosis, and could therefore exacerbate cellular dysfunction and thereby promote neurodegeneration.

Abstract Background In primary aldosteronism (PA), excessive, autonomous secretion of aldosterone is not suppressed by salt loading or fludrocortisone. For seated saline suppression testing (SSST), the recommended diagnostic cutoff 4-hour plasma aldosterone concentration (PAC) measured by high-performance liquid chromatography–mass spectrometry (HPLC-MS/MS is 162 pmol/L. Most diagnostic laboratories, however, use immunoassays to measure PAC. The cutoff for SSST using immunoassay is not known. We hypothesized that the cutoff is different between the assays. Methods We analyzed 80 of the 87 SSST tests that were performed during our recent study defining the HPLC-MS/MS cutoff. PA was confirmed in 65 by positive fludrocortisone suppression testing (FST) and/or lateralization on adrenal venous sampling and excluded in 15 by negative FST. PAC was measured by a chemiluminescence immunoassay (PACIA) in the SSST samples using the DiaSorin Liaison XL analyzer, and receiver operating characteristics (ROC) analysis was performed to identify the PACIA cutoff. Results ROC revealed good performance (area under the curve = 0.893; P < .001) of 4-hour postsaline PACIA for diagnosis of PA and an optimal diagnostic cutoff of 171 pmol/L, with sensitivity and specificity of 95.4% and 80.0%, respectively. A higher cutoff of 217 pmol/L improved specificity (86.7%) with lower sensitivity (86.2%). PACIA measurements strongly correlated with PAC measured by HPLC-MS (r = 0.94, P < .001). Conclusions A higher diagnostic cutoff for SSST should be employed when PAC is measured by immunoassay rather than HPLC-MS/MS. The results suggest that (i) PA can be excluded if 4-hour PACIA is less than 171 pmol/L, and (ii) PA is highly likely if the PACIA is greater than 217 pmol/L by chemiluminescence immunoassay. A gray zone exists between the cutoffs of 171 and 217 pmol/L, likely reflecting a lower specificity of immunoassay.

Salt sensitivity refers to the physiological trait present in mammals, including humans, by which the blood pressure (BP) of some members of the population exhibits changes parallel to changes in salt intake. It is commoner in elderly, females, Afro-Americans, patients with chronic kidney disease (CKD) and insulin resistance. Increased salt intake promotes an expansion of extracellular fluid volume and increases cardiac output. Salt-sensitive individuals present an abnormal kidney reaction to salt intake; the kidneys retain most of the salt due to an abnormal over-reactivity of sympathetic nervous system and a blunted suppression of renin–angiotensin axis. Moreover, instead of peripheral vascular resistance falling, salt-sensitive subjects present increased vascular resistance due mainly to impaired nitric oxide synthesis in endothelium. Recent studies have shown that part of the dietary salt loading accumulates in skin. Hypertensive and patients with CKD seem to have more sodium in skin comparing to healthy ones. However, we still have not fully explained the link between skin sodium, BP and salt sensitivity. Finally, although salt sensitivity plays a meaningful role in BP pathophysiology, it cannot be used by the physician in everyday patient’s care, mainly due to lack of a simple and practical diagnostic test.

Agricultural fields in drylands are challenged globally by limited freshwater resources for irrigation and also by elevated soil salinity and sodicity. It is well known that pedogenic carbonate is less soluble than evaporate salts and commonly forms in natural drylands. However, few studies have evaluated how irrigation loads dissolved calcium and bicarbonate to agricultural fields, accelerating formation rates of secondary calcite and simultaneously releasing abiotic CO 2 to the atmosphere. This study reports one of the first geochemical and isotopic studies of such “anthropogenic” pedogenic carbonates and CO 2 from irrigated drylands of southwestern United States. A pecan orchard and an alfalfa field, where flood-irrigation using the Rio Grande river is a common practice, were compared to a nearby natural dryland site. Strontium and carbon isotope ratios show that bulk pedogenic carbonates in irrigated soils at the pecan orchard primarily formed due to flood-irrigation, and that approximately 20–50% of soil CO 2 in these irrigated soils is calcite-derived abiotic CO 2 instead of soil-respired or atmospheric origins. Multiple variables that control the salt buildup in this region are identified and impact the crop production and soil sustainability regionally and globally. Irrigation intensity and water chemistry (irrigation water quantity and quality) dictate salt loading, and soil texture governs water infiltration and salt leaching. In the study area, agricultural soils have accumulated up to 10 wt% of calcite after just about 100 years of cultivation. These rates will likely increase in the future due to the combined effects of climate variability (reduced rainfall and more intense evaporation), use of more brackish groundwater for irrigation, and reduced porosity in soils. The enhanced accumulation rates of pedogenic carbonate are accompanied by release of large amounts of abiotic CO 2 from irrigated drylands to atmosphere. Extensive field studies and modelling approaches are needed to further quantify these effluxes at local, regional and global scales.

Excessive salt intake has been associated with the development of non-communicable diseases, including hypertension with several cardiovascular consequences. Although the detrimental effects of high salt on the skeleton have been reported, longitudinal assessment of calcium balance together with changes in bone microarchitecture and strength under salt loading has not been fully demonstrated. To address these unanswered issues, male Sprague–Dawley rats were fed normal salt diet (NSD; 0.8% NaCl) or high salt diet (HSD; 8% NaCl) for 5 months. Elevation of blood pressure, cardiac hypertrophy and glomerular deterioration were observed in HSD, thus validating the model. The balance studies were performed to monitor calcium input and output upon HSD challenge. The HSD-induced increase in calcium losses in urine and feces together with reduced fractional calcium absorption led to a decrease in calcium retention. With these calcium imbalances, we therefore examined microstructural changes of long bones of the hind limbs. Using the synchrotron radiation x-ray tomographic microscopy, we showed that trabecular structure of tibia and femur of HSD displayed a marked increase in porosity. Consistently, the volumetric micro-computed tomography also demonstrated a significant decrease in trabecular bone mineral density with expansion of endosteal perimeter in the tibia. Interestingly, bone histomorphometric analyses indicated that salt loading caused an increase in osteoclast number together with decreases in osteoblast number and osteoid volume. This uncoupling process of bone remodeling in HSD might underlie an accelerated bone loss and bone structural changes. In conclusion, long-term excessive salt consumption leads to impairment of skeletal mass and integrity possibly through negative calcium balance.

Hydrogels, possessing high biocompatibility and adaptability to biological tissue, show great usability in medical applications. In this research, a series of novel cross-linked chitosan quaternary ammonium salt loading with gentamicin sulfate (CTMCSG) hydrogel films with different cross-linking degrees were successfully obtained by the reaction of chitosan quaternary ammonium salt (TMCS) and epichlorohydrin. Fourier transform infrared spectroscopy (FTIR), thermal analysis, and scanning electron microscope (SEM) were used to characterize the chemical structure and surface morphology of CTMCSG hydrogel films. The physicochemical property, gentamicin sulphate release behavior, cytotoxicity, and antibacterial activity of the CTMCSG against Escherichia coli and Staphylococcus aureus were determined. Experimental results demonstrated that CTMCSG hydrogel films exhibited good water stability, thermal stability, drug release capacity, as well as antibacterial property. The inhibition zone of CTMCSG hydrogel films against Escherichia coli and Staphylococcus aureus could be up to about 30 mm. Specifically, the increases in maximum decomposition temperature, mechanical property, water content, swelling degree, and a reduction in water vapor permeability of the hydrogel films were observed as the amount of the cross-linking agent increased. The results indicated that the CTMCSG-4 hydrogel film with an interesting physicochemical property, admirable antibacterial activity, and slight cytotoxicity showed the potential value as excellent antibacterial wound dressing.

The 15 January 2022 submarine eruption at Hunga volcano was the most explosive volcanic eruption in 140 years. It involved exceptional magma and seawater interaction throughout the entire submarine caldera collapse. The submarine volcanic jet breached the sea surface and formed a subaerial eruptive plume that transported volcanic ash, gas, sea salts and seawater up to ~ 57 km, reaching into the mesosphere. We document high concentrations of sea salts in tephra (volcanic ash) collected shortly after deposition. We also discuss the potential climatic consequences of large-scale injection of salts into the upper atmosphere during submarine eruptions. Sodium chloride in these volcanic plumes can reach extreme concentrations, and dehalogenation of chlorides and bromides poses the risk of long-term atmospheric and weather impact. Salt content in rapidly collected tephra samples may also be used as a proxy to estimate the water:magma ratio during eruption, with implications for quantification of fragmentation efficiency in submarine breaching events. The balance between salt loading into the atmosphere versus deposition in ash aggregates is a key factor in understanding the atmospheric and climatic consequences of submarine eruptions.

Until the beginning of this century, neurons of the supraoptic nucleus (SON) were repeatedly shown to express tyrosine hydroxylase (TH) in salt loaded rats. However, its role remains unsolved due to methodological problems. Given that these issues can now be solved using transgenic mice and more advanced methods, the aim of this study was to reproduce the salt loading models used in rats, in C57BL/6 mice and transgenic mice expressing the green fluorescent protein gene under the TH promoter. Our study also attempted to identify a model that would most significantly increase TH synthesis in vasopressinergic neurons. This was assessed with immunocytochemistry by measuring the number of TH-immunoreactive neurons in the SON and the intraneuronal content of TH-immunoreactive material in individual neurons. In the first model, when using 3% NaCl as drinking water, the highest number of TH-immnopositive neurons was detected on the 3rd day, while the intraneuronal TH content did not change. In the second model, 10 hours after the intraperitoneal administration of 8.5% NaCl (experiment) or 0.9% NaCl (control), the number of TH-immunopositive neurons was significantly higher than in the first model. Moreover, the intraneuronal content of TH increased. Additional PCR analysis showed in the second model an increase in the expression of the TH gene and genes of some transcription factors (Sp1, Atf4, c-Fos, c-Jun) that initiate the TH gene expression in SON. Thus, we developed and characterized a salt loading model in mice with the highest level of TH synthesis, which will be used in the future to assess the functional significance of this protein.

Primary aldosteronism (PA) is the most common form of endocrine hypertension. The available animal models of PA rely on gene manipulation, thus fail to duplicate the general pathological process of PA in humans. Meriones unguiculatus (MU) has been reported to possess a large size of adrenal gland and an elevated ability to save water. In this study, we aimed to confirm whether MU can serve as an ideal animal model of PA. Sprague Dawley rats of the same body weight (SD1) or age (SD2) as MU were used as control groups. Blood pressure and serum aldosterone, renin and electrolyte levels were measured, and the oral salt loading test was used as confirmatory test to compare the inhibition level of the renin angiotensin aldosterone system (RAAS) among the three groups. The expression and distribution of CYP11B2 (aldosterone synthase) were evaluated in the adrenal gland of each group. MU exhibited typical clinical manifestations of PA, including hypertension, hyperaldosteronism, low renin levels and strong sodium retention and potassium excretion abilities. Compared with control groups, the inhibitory effect of a high-sodium diet on the RAAS was milder in MU, accompanied by significant cardiac dysfunction. The protein expression level and distribution area of CYP11B2 were significantly increased in the adrenal gland of MU. The current study reveals that MU could serve as an ideal spontaneous PA model. The increased expression and distribution of CYP11B2 stimulate the excessive aldosterone production in a renin-independent manner, leading to a significant increase in blood pressure in MU.

New Findings What is the central question of this study? Is the cardiovascular phenotype of high blood pressure observed in rats salt loaded with 2% NaCl in drinking solution a blood volume‐dependent hypertension? What is the main finding and its importance? Animals exposed to 2% NaCl drinking solution develop hypertension, with dominance of sympathetic outflow and high [Na+] in the cerebrospinal fluid, but without changes in the blood volume. The phenotype of salt‐dependent hypertension might be related to accumulation of [Na+] in the cerebrospinal fluid, which makes it an interesting animal model in which to study the neuronal pathways involved in control of the circulation in osmotic challenge conditions. Evidence suggests that hypertension induced by high salt intake is correlated with an autonomic imbalance that favours sympathetic hyperactivity and an increase in vascular resistance, indicating a neurogenic component to this pathology. Although there are several animal models in which to study salt‐induced hypertension with prolonged exposure to a high‐sodium diet, here we sought to investigate whether the increase in arterial blood pressure of rats subjected to a short exposure to high salt, with 2% NaCl drinking solution instead of water, relies on changes in the circulating blood volume. Male Wistar rats were divided randomly into three groups: euhydrated (EU, n = 10), salt loaded (SL, n = 13) and water deprived (WD, n = 6). The SL rats exhibited a significant increase in mean arterial blood pressure, with a large low‐frequency component of systolic arterial blood pressure variability, when compared with the EU group. Circulating blood volume did not differ between SL and EU rats, but it was lower in WD rats. Compared with EU rats, the [Na+] in cerebrospinal fluid was higher in SL rats and similar in magnitude to the WD rats. Plasma [Na+] did not differ between SL and EU rats, but it was higher in WD rats. Collectively, our data suggest that the hypertension induced by a short exposure to high salt intake closely resembles a neurogenic mechanism, but not a blood volume‐dependent mechanism, with cumulative [Na+] in the cerebrospinal fluid that could be associated with changes in the neurochemistry of autonomic nuclei, which are highly susceptible to osmotic stress related to high salt consumption.