High Salt Intake Research Articles

The brain and hypertension: how the brain regulates and suffers from blood pressure.

The brain plays several roles in the relationship between blood pressure (BP) and the brain: it acts as the control center for BP regulation, a target organ in hypertension, and a crucial component for cognitive function. This mini-review introduces recent findings on "brain and hypertension" from Hypertension Research and other journals. Activation of the angiotensin II type 1 receptor (AT1R) signaling pathway in the brain causes sympathoexcitation and hypertension. AT1R-associated protein and β-arrestin promote AT1R internalization and suppress AT1R signaling, with brain-specific roles in BP regulation. The brain receives various inputs from the peripheral system, including the heart and kidneys, and controls central sympathetic outflow. The brain mechanism involved in the enhanced cardiac sympathetic afferent reflex and the beneficial effects of renal denervation have been demonstrated. The brain's vulnerability in hypertension includes stroke, with cerebral small vessel disease (SVD) contributing to stroke risk and brain changes. Sex differences and the age of hypertension onset influence these outcomes. High salt intake exacerbates hypertension and stroke risk, with central mechanisms like sympathoexcitation implicated. Hypertension significantly impacts cognitive function, linking to cerebral SVD and cognitive decline. Orthostatic BP regulation abnormalities also emerge as early risk markers for dementia. Improved BP control in hypertensive individuals can significantly reduce the risk of stroke and cognitive decline, as well as cardiovascular disease, enhancing overall brain health and quality of life. Further understanding the brain's role in BP regulation and the pathogenesis of hypertension will facilitate the development of novel hypertension treatments and prevention strategies.

The influence of the daily salt-intake on the antihypertensive action and atrial natriuretic peptide level in patietns with angiotensin receptor neprilysin inhibition

Abstract Background The angiotensin receptor–neprilysin inhibitor (ARNI) is a drug which acts through angiotensin receptor blocking effect and the increase in atrail natriuretic peptide (ANP) through neprilysin inhibitor in hypertension (HT). These combined effects result in a reduced risk of hospitalization for heart failure or death from cardiovascular causes. ANP is also known for its various cardioprotective effects including vasodilator and natriuretic action. Acording to Guyton's pressure-natriuresis curve, the efficacy of angiotensin receptor blocker drugs is diminished in HT cases with high daily salt inatke. However, whether the effect of ARNI on HT is attenuated in patients with high daily salt intake remains unclear. Purpose The present study investigated the influence of a daily salt intake on the antihypertensive action and ANP level in patients with ARNI. Methods Fourty-four consecutive essential HT patients on ARNI were enrolled. Blood pressure and ANP level were measured at baseline (before taking ARNI) and 3 weeks later. ARNI (200mg) was prescribed and maintained during the study. In addtion, the daily salt intake was calculated using creatinine and natrium levels in urine, age, and body weight according to Japanese hypertensive guideline at baseline and 3 weeks later. Results The average age was 70±8 years old. About 50% (N=23) was male. The mean sytolic and diastolic blood pressure was 148±14mmHg and 89±10mmHg, respectively. The mean daily salt intake was 9.5±2.2 g/day at baseline. The mean ANP level was 529±300pg/ml. At follow up (3 weeks later), the mean systolic and diastolic blood pressure significanly went down to 132± 18 mmHg and 70± 9 mmHg, respectively (p=0.03). ANP level also increased from 529±300pg/ml to 793±580pg/ml. However, the mean daily salt intake was almost same as the baseline at 9.4±3.2 g/day. The patients were divided into 2 groups; high daily salt intake (N=20 with mean daily salt intake 10.5±1.7g/day)) and low daily salt intake (N=24 with 8.4±3.1g/day) groups compared to the baseline. The absolute and percentage changes in systolic blood pressure were almost same in the high and low daily salt intake groups (-12.7±15.8mmHg vs -13.7±14.2mmHg, p=0.75; -5.8±6.5% vs.-7.0±9.6%, p=0.58, respectively). However, the change rate in ANP level was significantly higer in the high daily salt intake group than in the low daily salt intake group (155±63 vs. 12±16%, p=0.01). Conclusion ARNI demonstrates effectiveness in lowering the blood pressure even in patients with higher salt intake, unlike angiotensin receptor blocker. In cases with high salt intake, the notable increase in ANP levels may contribute to decreasing blood pressure through vasodilator and natriuretic action.

The association between the dietary salt intake and glucose intolerance in the non-diabetic populations: from the Korean National Health and Nutritional Examination Survey (KNHANES)

Abstract Background Diabetes is known to be a strong risk factor for cardiovascular disease (CVD), and controlling salt intake in patients with type 2 diabetes may be a strategy to reduce the risk of CVD. However, the clear interaction between salt intake and glucose homeostasis has yet to be investigated. Our study evaluated the frequency and risk of glucose intolerance (pre-diabetes) according to dietary salt intake in the non-diabetic population in Korea. Methods The Korean National Health and Nutritional Examination Survey (KNHANES) database was utilized for this study (https://knhanes.cdc.go.kr). A total of 72,751 subjects were enrolled in the KNHANES database from 2010 to 2018. The subjects were categorized into the following: normal fasting glucose (i.e., no pre-diabetes; FPG < 100 mg/dL), stage 1 pre-diabetes (FPG 100–109 mg/dL), stage 2 pre-diabetes (FPG 110–125 mg/dL). All subjects were divided into 8-equal groups according to their sodium intake: Group 1: ≤ 3.5 g, Group 2: 3.5 to 5.0 g, Group 3: 5.0 to 6.3 g, Group 4: 6.3 to 7.8 g, Group 5: 7.8 to 9.5 g, Group 6: 9.5 to 11.8 g, Group 7: 11.8 to 15.5 g, Group 8: > 15.5 g. This study is a retrospective cross-sectional study, so future risks cannot be assessed, but only the disease status assessment at the same time. Results Of the total 57,165 subjects without diabetes, 29.5% (16,874 subjects) were pre-diabetic, of which 22.0% (12,577 patients) were stage I pre-diabetic, and 7.5% (4,297 subjects) were stage II pre-diabetic. From the lowest salt intake group (group 1, salt intake <3.5g) to the highest salt intake group (group 8, salt intake>.5g), the pre-diabetes prevalence continuously increased from 22.9% to 33.3%. The range of stage 1 pre-diabetes was 16.4% to 26.4%, and the range of stage 2 diabetes was 6.5% to 8.7%. The odds ratio (OR) of pre-diabetic risk according to salt intake in the non-diabetic population, compared with group 1, group 2 was 1.16 (95% confidence interval [CI]: 1.07-1.25), group 3 was 1.32 (95% CI: 1.23 -1.43), group 4 was 1.46 (95% CI: 1.35-1.57), group 5 was 1.51 (95% CI: 1.40-1.63), group 6 was 1.57 (95% CI: 1.46-1.69), group 7 was 1.65 (95% CI: 1.53-1.78), group 8 was 1.68 (95% CI: 1.56-1.81). Conclusions High salt intake is significantly associated with pre-diabetes prevalence in the non-diabetic Korean population.

The association between the dietary salt intake and glucose intolerance in healthy populations: from the Korean National Health and Nutritional Examination Survey (KNHANES)

Abstract Background Diabetes is known to be a strong risk factor for cardiovascular disease (CVD), and controlling salt intake in patients with type 2 diabetes may be a strategy to reduce the risk of CVD. However, the clear interaction between salt intake and glucose homeostasis has yet to be investigated. Our study evaluated the frequency and risk of glucose intolerance (pre-diabetes) according to dietary salt intake in a healthy population in Korea. Methods The Korean National Health and Nutritional Examination Survey (KNHANES) database was utilized for this study (https://knhanes.cdc.go.kr). A total of 72,751 subjects were enrolled in the KNHANES database from 2010 to 2018. The subjects were categorized into the following: normal fasting glucose (i.e., no pre-diabetes; FPG < 100 mg/dL), stage 1 pre-diabetes (FPG 100–109 mg/dL), stage 2 pre-diabetes (FPG 110–125 mg/dL). All subjects were divided into 8-equal groups according to their sodium intake: Group 1: ≤ 3.5 g, Group 2: 3.5 to 5.0 g, Group 3: 5.0 to 6.3 g, Group 4: 6.3 to 7.8 g, Group 5: 7.8 to 9.5 g, Group 6: 9.5 to 11.8 g, Group 7: 11.8 to 15.5 g, Group 8: > 15.5 g. This study is a retrospective cross-sectional study, so future risks cannot be assessed, but only the disease status assessment at the same time. Results Of the total 36,782 healthy adults, 17.6% (6,481 subjects) were pre-diabetic, of which 14.7% (5,397 subjects) were stage I pre-diabetic, and 2.9% (1,084 patients) were stage II pre-diabetic. From the lowest salt intake group (group 1, salt intake <3.5g) to the highest salt intake group (group 8, salt intake>.5g), the pre-diabetes prevalence continuously increased from 9.2% to 22.8%. The range of stage 1 pre-diabetes was 7.3% to 18.3%, and stage 2 diabetes was 1.9% to 4.5%. The odds ratio (OR) of pre-diabetic risk according to salt intake in the non-diabetic population, compared with group 1, group 2 was 1.46 (95% confidence interval [CI]: 1.30-1.68), group 3 was 1.84 (95% CI: 1.62 -2.08), group 4 was 2.24 (95% CI: 1.99-2.54), group 5 was 2.43 (95% CI: 2.15-2.75), group 6 was 2.49 (95% CI: 2.20-2.81), group 7 was 2.83 (95% CI: 2.51-3.19), group 8 was 2.90 (95% CI: 2.57-3.27). Conclusions High salt intake is significantly associated with pre-diabetes prevalence in healthy Korean population.

High chloride induces aldosterone resistance in the distal nephron.

Increasing the dietary intake of K+ in the setting of a high salt intake promotes renal Na+ excretion even though K+ concurrently enhances the secretion of aldosterone, the most effective stimulus for renal Na+ reabsorption. Here, we questioned whether in the high salt state a mechanism exists, which attenuates the aldosterone response to prevent renal Na+ reabsorption after high K+ intake. Mice were fed diets containing varying amounts of Na+ combined with KCl or KCitrate. Murine cortical connecting duct (mCCDcl1) cells were cultured in media containing normal or high [Cl-]. The response to aldosterone was analyzed by high-resolution imaging and by biochemical approaches. The canonical cellular response to aldosterone, encompassing translocation of the mineralocorticoid receptor (MR) and activation of the epithelial Na+ channel ENaC was repressed in Na+-replete mice fed a high KCl diet, even though plasma aldosterone concentrations were increased. The response to aldosterone was restored in Na+-replete mice when the extracellular [Cl-] increase was prevented by feeding a high KCitrate diet. In mCCDcl1 cells, an elevated extracellular [Cl-] was sufficient to disrupt the aldosterone-induced MR translocation. These findings indicate a pivotal role for extracellular [Cl-] in modulating renal aldosterone signaling to adapt MR activation by a high K+ intake to the NaCl balance. An impairment of [Cl-]-mediated aldosterone resistance may contribute to excessive MR activation by aldosterone in the presence of a high salt intake characteristic of the Western diet, resulting in an inappropriate salt reabsorption and its downstream detrimental effects.

Transient High Salt Intake Promotes T-Cell-Mediated Hypertensive Vascular Injury.

Dietary high salt (HS) intake has a strong impact on cardiovascular diseases. Here, we investigated the link between HS-aggravated immune responses and the development of hypertensive vascular disease. ApolipoproteinE-deficient mice were transiently treated with HS (1% NaCl) via drinking water for 2 weeks, followed by a washout period, and subsequent Ang II (angiotensin II) infusion (1000 ng/kg per min for 10 days) to induce abdominal aortic aneurysms/dissections and inflammation. While transient HS intake alone triggered nonpathologic infiltration of activated T cells into the aorta, subsequent Ang II infusion increased mortality and the incidence of abdominal aortic aneurysms/dissections and atherosclerosis compared with hypertensive control mice. There were no differences in blood pressure between both groups. In transient HS-treated hypertensive mice, the aortic injury was associated with increased inflammation, accumulation of neutrophils, monocytes, CD69+CD4+ T cells, as well as CD4+ and CD8+ memory T cells. Mechanistically, transient HS intake increased expression levels of aortic RORγt as well as splenic CD4+TH17 and CD8+TC1 T cells in Ang II-treated mice. Isolated aortas of untreated mice were incubated with supernatants of TH17, TH1, or TC1 cells polarized in vitro under HS or normal conditions which revealed that secreted factors of HS-differentiated TH17 and TC1 cells, but not TH1 cells accelerated endothelial dysfunction. Our data suggest that transient HS intake induces a subclinical T-cell-mediated aortic immune response, which is enhanced by Ang II. We propose a 2-hit model, in which HS acts as a predisposing factor to enhance hypertension-induced TH17 and TC1 polarization and aortic disease.

Barriers and enablers to salt intake reduction in Australian adults with high blood pressure.

High dietary salt intake is a known risk factor for hypertension. However, Australians continue to consume excessive amounts of salt. The purpose of this study was to identify barriers, enablers and strategies to reduce salt in a sample of Australian adults with hypertension. This was a qualitative study. Participants were asked a set of open-ended questions during focus groups conducted between October 2020 and April 2021. Sessions were recorded and transcribed. Using an inductive approach, the transcript data from the focus groups were thematically analysed. This involved checking accuracy, becoming familiar with the data, coding responses based on questions, identifying themes through common patterns and validating themes by grouping similar questions that represented the data and study aim effectively. Thirty-one adults (55 % females) with high blood pressure participated in the focus group discussions. Participants demonstrated good knowledge of high blood pressure risk factors but lacked an understanding of recommended salt intake levels and sources of hidden salt. Challenges in reducing salt intake included the limited availability of low-salt commercial foods. Participants suggested improved food labelling and the use of technology-based interventions to promote healthier choices. Findings highlight the need for behavioural interventions, policy reforms and collaborations between the government, food industries and health organisations to address high salt intake in the population.

Exploring Dietary Salt Knowledge, Attitude, and Practices among People of African Descent in the United Kingdom: A Qualitative Study.

Background/Objectives: People of African Descent (PoAD) in the United Kingdom (UK) are at an increased risk of hypertension and cardiovascular disease (CVD), partly due to dietary habits such as high salt intake. This study sought to understand the dietary salt-related knowledge, attitudes, and practises (KAP) of PoAD in the UK, to inform the development of culturally tailored interventions to reduce dietary salt intake in this population. Methods: We collected data on KAP from 21 PoAD across various regions in the UK through online semi-structured interviews and analysed them using reflexive thematic analysis (TA). Results: The age of the participants ranged from 20 to 70 years (43 ± 11). Six overarching themes were identified: (i) the multifaceted roles of salt in culinary practises, (ii) the increased awareness of health risks associated with high salt intake, (iii) the existence of knowledge gaps regarding recommended daily salt intake, (iv) the cultural influences on salt consumption levels, (v) the lack of engagement with food labels, and (vi) a limited awareness of salt reduction initiatives. Conclusions: Our findings highlight the significance of salt in the culture and culinary practises of PoAD. Despite general awareness of the health risks of excessive salt consumption, there was a notable deficiency in knowledge about the recommended salt intake levels as well as minimal engagement with nutritional labelling. These findings underline a need for culturally sensitive health interventions that integrate culinary practises, beliefs, and preferences of PoAD, aiming to effectively reduce salt intake and mitigate associated health risks.

Excess dietary salt is associated with an altered bone strain index, degraded bone microarchitecture, vertebral fractures, and increased prevalence of osteoporosis in postmenopausal women-A study from a teaching hospital in southern India.

Excess dietary salt causes increased urinary calcium and this may lead to bone loss. We proposed to study the association between dietary salt intake and bone health in postmenopausal women from southern India. An observational study in which community-dwelling postmenopausal women were recruited. Daily salt intake and urine calcium/creatinine ratio were assessed. Bone biochemistry and densitometric parameters such as bone mineral density (BMD), trabecular bone score (TBS) vertebral fractures, and bone strain index (BSI) were assessed using Dual Energy X-Ray Absorptiometry (DXA). A total of 383 postmenopausal women with a mean ± SD age of 59.8 ± 7.2 years and BMI of 25.2 ± 4.6 kg/m2 were recruited. Among the participants, 165/383(43.1%) had osteoporosis at any site and 21% had moderate-severe vertebral fractures. The BMD at lumbar spine and femoral neck, TBS and BSI were significantly (p < 0.001) lower and the CTx was significantly (p = 0.008) higher among women with high salt intake (7.2 g/day) as compared to those with salt intake of <7.2 g/day. The prevalence of osteoporosis, low TBS, high BSI, and moderate-severe vertebral fractures significantly increased across low to high salt-intake categories. An ROC analysis showed that excess dietary salt was significantly associated with osteoporosis at any site with an AUC of 0.870 (95% CI: 0.832-0.907). On a multivariate analysis, excess salt intake conferred the highest odds of osteoporosis (OR: 2.296; 95% CI: 1.909-2.761). Excess dietary salt is associated with high urinary calcium and compromised bone health among postmenopausal women from southern India. This may be a modifiable risk factor in osteoporosis and warrants further research.

Microbiome-metabolome analysis insight into the effects of high-salt diet on hemorheological functions in SD rats.

The present study examined the effect of two dietary regimens with elevated salt concentrations (4% and 8% salt) on hemorheological functions of SD rats, and explored the underlying mechanisms mainly through microbiome-metabolome analysis. An 8% HSD substantially altered the hemorheological parameters, and compromised intestinal barrier integrity and reduced the short-chain fatty acid levels. The microbiome-metabolome analysis revealed that 49 genus-specific microorganisms and 156 metabolites showed a consistent trend after exposure to both 4% and 8% HSDs. Pathway analysis identified significant alterations in key metabolites within bile acid and arachidonic acid metabolism pathways. A two-sample Mendelian randomization (MR) analysis verified the link between high dietary salt intake and hemorheology. It also suggested that some key microbes and metabolites (such as Ruminococcaceae_UCG-005, Lachnospiraceae_NK4A136, Ruminiclostridium_6, and Ruminococcaceae_UCG-010, TXB-2, 11,12-diHETrE, glycochenodeoxycholate) may involve in abnormalities in blood rheology caused by high salt intake. Collectively, our findings underscored the adverse effects of high dietary salt on hemorheological functions and provide new insight into the underlying mechanism based on microbiome-metabolome analysis.

Soy lysolecithin prevents hypertension and cognitive impairment induced in mice by high salt intake by inhibiting intestinal inflammation

High salt (HS) intake induces hypertension and cognitive impairment. Preventive strategies include against dietary supplements. Soybean lecithin is a widely used phospholipid supplement. Lysolecithin is important in cell signaling, digestion, and absorption. This study aimed to investigate the effects of lysophosphatidylcholine containing >70% of the total phospholipids (LPC70), on hypertension and cognitive impairment induced in mice by HS intake. Mice were provided with HS solution (2% NaCl in drinking water) with or without LPC70 for 12 weeks. Blood pressure, cognitive function, and inflammatory response of intestine were determined. Hypertension and impaired object recognition memory induced by HS intake were implicated with increased inducible nitric oxide synthase in the small intestine and tau hyperphosphorylation in the prefrontal cortex. LPC70 treatment prevented cognitive impairment by suppressing inducible nitric oxide synthase and tau hyperphosphorylation. LPC70 may be valuable as a functional food component in preventing HS-induced cognitive impairment.

Predictors of sleepiness in a large-scale epidemiology study ESSE-RF.

To identify predictors of excessive daytime sleepiness we analyzed data from the 'Epidemiology of cardiovascular diseases in regions of Russia (ESSE-RF)' study. Data from participants of the cohort study ESSE-RF (2012-2013), aged 25-64 years, from 13 regions of Russia were analyzed (2012-2013). The participants were interviewed regarding their sleep complaints, including difficulties with initiating and maintaining sleep, sleepiness, and use of sleeping pills. Sleepiness was considered significant if it occurred at least three times a week. The examination encompassed social, demographic, and anthropometric measures, lifestyle factors, self-reported diseases, and laboratory parameters. The final analysis included 13,255 respondents. Frequent (≥3 times/week) sleepiness was reported by 5,8%, and occasional sleepiness (1-2 times/week) by 10.8% of respondents. Multivariate regression analysis identified significant predictors of frequent sleepiness. Sleep complaints (insomnia, sleep apnea, snoring) and frequent use of sleep medication were prominent factors. Additionally, age, female gender, higher education, and retirement status were associated with sleepiness. Beyond demographics and sleep, the analysis revealed predictors: abnormal anxiety levels, low high-density lipoprotein, high salt intake and following medical conditions: arrhythmia, hypertension, myocardial infarction, other heart diseases, and renal disease. This study identified a significant prevalence of EDS in Russians, aligning with global trends. However, findings suggest potential regional variations. Analysis revealed a complex interplay of factors contributing to EDS, highlighting the importance of individualized treatment approaches for improved sleep health.

Ethnic differences in knowledge, attitudes, and practices related to dietary salt intake and association with hypertension in Malaysia: a multi-centre cross-sectional study.

The association between high salt intake and elevated blood pressure levels has been well-documented. However, studies on how effectively this knowledge translates into actionable practices, particularly across different ethnic groups, remain limited. This study aimed to evaluate the knowledge, attitudes, and practices (KAP) towards dietary salt intake across ethnicities and determine its association with hypertension. 5128 Malaysian adults recruited from a national blood pressure screening study completed questionnaires on demographics, and KAP related to dietary salt intake. There were 57.4% Malay, 23.5% Chinese, 10.4% Indian, and 8.7% individuals of other ethnic groups. Overall, more than 90% of the participants knew that a high salt intake causes serious health problems, but only around one-third knew the relationship between high salt intake and strokes and heart failure. Participants of different ethnic groups displayed significant differences in the KAP domains, where Indians generally exhibited better knowledge, attitudes, and reported better practices such as reading salt labels and using spices. Those who were unaware of the difference between salt and sodium and who reported not reading salt labels had higher odds of having elevated blood pressure. These findings demonstrate that while there is a suboptimal translation of salt knowledge into practice in Malaysia, with significant differences in KAP observed between ethnic groups, the potential of improving health outcomes by improving the clarity and awareness of salt labels is substantial. Tailored education promoting salt-label reading, minimizing processed foods intake and discretionary salt use should be ethnic-specific to better curb this escalating hypertension epidemic.

Abstract P445: High Salt Intake Increases Arterial Stiffness Measured by Pulse Wave Velocity in Spontaneously Hypertension Rats

High salt intake represents an important risk factor for the development of hypertension. In this context, the present study aimed to evaluate the impacts of high salt intake on cardiovascular and arterial parameters in spontaneously hypertensive rats (SHR), through pulse wave velocity analysis. Male Wistar rats and SHR were divided into groups drinking water Control (Wistar/C and SHR/C), or Salt (1% NaCl Wistar/S and SHR/S). Rats underwent measurement of systolic blood pressure (SBP) at baseline, 30 and 60 days by plethysmography. After 60 days, rats were catheterized (carotid and femoral arteries) for haemodynamic measurements. The non-invasive SBP was enhanced in SHR after 30 days of salt treatment (SHR/C 200 ± 5.2 vs. SHR/S 218 ± 3.2 mmHg, P&lt;0.01) as at 60 days (SHR/C 206 ± 5.8 vs. SHR/S 225 ± 3.3 mmHg, P&lt;0.05). Arterial stiffness was augmented in SHR rats with 60 days of salt treatment, corresponding to 8% in the pulse wave velocity measurement (SHR/C 6.2 ± 0.2 vs. SHR/S 6.7 ± 0.3 m /s), and 11% in pulse pressure (SHR/C 54 ± 1.3 vs. SHR/S 60 ± 1.7 mmHg). These findings support the hypothesis that high salt intake is related to detrimental haemodynamic and arterial stiffness in SHR and highlights potential novel mechanism enrolled on the pathogenesis and progression of hypertension.

Abstract MP32: Megalin and lysosomal disruption in the kidney epithelial cells of high salt diet fed rats: protective role of angiotensin II type 2 receptor

Earlier we have reported that 2-days high salt diet (HSD) feeding caused proteinuria in obese rats and the AT 2 R agonist treatment prevented proteinuria. Since HSD feeding for 2 days and the AT 2 R activation did not affect blood pressure, GFR, glomerular structure, and inflammation, the mechanism responsible for proteinuria remains unknown. Megalin is a proximal tubule epithelial cells endocytic receptor responsible for filtered protein reabsorption. The absorbed proteins are directed to lysosomes for degradation. Lysosomes is a nutrient sensing subcellular compartment and a critical part of the endocytic machinery and cellular trafficking. We hypothesized that high salt intake caused lysosomal stress, which negatively impacted megalin-protein cellular trafficking and thus caused proteinuria. Therefore, we evaluated the markers of lysosomal stress and megalin expression in the proximal tubules of HSD fed obese Zucker rats. Urinary excretion of N-acetyl-glucosaminidase (NAG), which is a marker of lysosomal injury and oxidative stress, was significantly increased in HSD fed rats compared with normal salt diet (NSD: 16.6 vs HSD: 40.5 RFU/hr/µg Cr). This increase was associated with an increase in another oxidative stress marker H 2 O 2 in the urine (NSD: 0.37 vs HSD: 1.72 ΔRFU/min). Confocal analysis revealed that megalin was localized in the lysosomes in HSD fed rats, as megalin was co-localized with the lysosomal marker LAMP-1 in the proximal tubules. Moreover, in HSD fed rats there was a remarkable increase (2-fold) in the lysosomal size (fig) and number per tubule (NSD: 18 vs HSD: 48). The AT 2 R agonist C21 (0.3 mg/Kg/day, i.p.) treatment of HSD-fed rats restored surface megalin expression, reduced urinary NAG and H 2 O 2 and the lysosomal number and size. Our in vitro studies performed in OK cells (proximal tubule epithelial cells) treated with high NaCl (100 mM) without/with the AT 2 R agonist C21 (1µM) also revealed that compared to NSD, high NaCl reduced megalin surface expression and C21 treatment prevented it. We conclude that high salt intake causes lysosomal stress. Particularly, large lysosomal size potentially is affecting endocytic machinery, including impairing megalin-protein dissociation and megalin recycling, thus causing proteinuria.

O14 KIDNEY RESIDENT MEMORY T CELLS MEDIATE THE CHRONIC PROGRESSION OF HYPERTENSION

A significant challenge in treating hypertension is insufficient blood pressure (BP) control and its recurrence. Previously, we described the contribution of CD8 T cells (CD8Ts) to the pathogenesis of salt-sensitive hypertension. Notably, despite antihypertensive therapy temporarily lowering BP in hypertensive mice, the T cell residency was not disrupted within the kidneys, and hypertension recurred when treatment was ceased. We hypothesize that the CD8Ts established a long-living resident memory (Trm) population in the kidney that instigates the recurrence of hypertension. To examine this, we utilized both wild-type (WT) and T-cell-specific KO of TGFβRII (Tsp-TGFβRKO) mice, which prevents the formation of Trms. Blood pressure was recorded continuously with radiotelemetry. Hypertension was induced with the classic DOCA-salt model and an Angiotensin II (Ang II)-induced salt memory model to mimic the clinical recurrence of hypertension with high salt intake. In this salt-memory model, a one-week infusion of Ang II paired with high salt-induced hypertension before being allowed to return to normal blood pressure. A chronic high salt intake challenge then tested the recurrence of hypertension. Both splenic and renal T cell populations were characterized using flow cytometry. As expected, DOCA-salt treatment led to salt-sensitive hypertension in WT mice along with the development of a significant CD8Trm population within their kidneys. These CD8Trms were notably diminished in the kidneys of DOCA-treated Tsp-TGFβRKO mice who also had attenuated blood pressure elevation. While testing the recurrence of hypertension during the Ang II-induced salt-memory model both WT and Tsp-TGFβKO reached the same degree of hypertension during Ang II-salt and baseline blood pressure before and after Ang II-salt. However, only the WT developed Trm and had the recurrence of hypertension with high salt challenge whereas both were lost in the Tsp-TGFβKO mice. In summary, our study unveils the critical role of kidney CD8Trms in contributing to salt-sensitive hypertension and its recurrence. This leads to targeting key molecules that initiate the development of Trms to mitigate the persistency of hypertension.

Abstract P219: Risk factors for Accelerated Vascular Aging in Resistant Hypertension: Should we screen our patients earlier?

Background: There is an increase in Cardiovascular disease(CVD) mortality rates among young adults worldwide. Patients with resistant hypertension (RHTN) are at particularly high risk for CVD compared to those with more easily controlled hypertension (HTN). RHTN is defined as blood pressure above goal despite using ≥3 antihypertensive medications. The role of accelerated vascular aging (AVA) in this group has not been well investigated. Our study aims to evaluate risk factors for AVA and its role in RHTN. Methods: We conducted a cross-sectional analysis of a large cohort of 965 black and white patients with RHTN referred to the RHTN Clinic at the University of Alabama at Birmingham. Patients with HTN served as a control group. Results: The most compelling data was seen in young patients (age 41-55 yrs). Those with RHTN had significantly higher arterial stiffness than patients with HTN (pulse pressure: 63.3±17.9 vs 51.2 ±11.7 mm Hg, p=&lt;0.001) earlier onset of HTN (34.2 ±7.3 vs 39.4±10.3 yrs, p=0.001) and longer duration (15.5±9.6 vs 10.7±9.0 yrs, p=0.001), higher BMI (35.4±8.3 vs 31.9±6.6 kg/m2), higher Aldosterone Renin Ratio (12.4±13.2 vs 7.9±12.9, p=0.026), and 24-hour urinary sodium excretion (217.2±104.6 vs 182.8±77.2 mmol, p=0.036). Conclusion: Younger patients with RHTN, when compared with HTN, seem to have AVA as evidenced by higher prevalance of obesity, arterial stiffness, overactivation of the renin-angiotensin-aldosterone system, and higher salt intake. Earlier screening, starting at the age of 35 yrs, may help detect AVA quicker and prevent complications associated with RHTN in younger adults

68 - The Effects of High Salt Intake on Antidiabetic Medication

68 - The Effects of High Salt Intake on Antidiabetic Medication

Abstract P182: Antigen Presenting Cell-specific Keap1-Nrf2 pathway Mediates Salt-Sensitive Hypertension in Humans

Background: Hypertension remains the leading cause of mortality worldwide and is a primary risk factor for cardiovascular disease. Of the 1.3 billion people globally affected by hypertension, over 50% exhibit salt-sensitivity of blood pressure (SSBP), which leads to higher rates of mortality, morbidity, and kidney damage compared to those with salt-resistant hypertension. Previously our research has shown that high salt intake activates antigen-presenting cells (APCs), causing inflammation and hypertension. This pro-inflammatory response is partly driven by the epithelial sodium channel (ENaC), which facilitates sodium ion transport into APCs. While the Keap1-Nrf2 pathway is known for its role in antioxidant defense and inflammatory responses, its contribution to salt-sensitive hypertension remains unclear. We hypothesize that ENaC-dependent sodium entry triggers inflammation and activates the Sp1-MALAT1-Keap1-Nrf2 signaling axis in APCs, thereby contributing to SSBP. Method: We utilized a well-established inpatient protocol to phenotype participants for salt sensitivity of blood pressure. Additionally, we conducted RNA sequencing (RNAseq) on human monocytes exposed to elevated sodium levels in vitro and performed Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) analysis on peripheral blood mononuclear cells (PBMCs). Results: We found that whereas high salt did not significantly increases expression of Sp1 (5380.63 ± 359.77 vs 7414.54 ± 434.19, q=0.829), MALAT1 (86888.54 ±12200.12 vs 219429.90 ± 109994.16, q=0.717), Keap1 (1586.54 ± 132.94 vs 2203.72 ± 177.48, q=0.884), it significantly increased Nrf2 expression (5080.36 ± 416.64 vs 5443.54 ± 432.78, q=0.019) in RNAseq analysis of human high salt compared to normal salt treated monocyte. Furthermore, the results of the CITE-seq experiment indicated that changes in the expression of the Sp1 correlate with SSBP (r=0.5205, p=0.038). Conclusion: These preliminary findings reveal a physiological link between inflammation and salt-sensitive hypertension through the Sp1-MALAT1-Keap1-Nrf2 signaling axis in APCs. The activation of APCs mediated by Sp1 could potentially serve as a diagnostic marker for salt sensitivity in blood pressure.

Burden of noncommunicable diseases and COVID-19 pandemic prevention and control strategies

Noncommunicable diseases (NCDs) are the leading cause of death in 21st century. The risk factors for development and progression of NCDs include sedentary lifestyle, inadequate fruits and vegetables intake, tobacco use, high blood pressure, high total cholesterol levels, obesity, high salt intake, low physical activity, and air pollution. People with NCDs and comorbidities like hypertension, cardiovascular diseases, diabetes, chronic respiratory infection and cancer are more vulnerable to severe COVID-19 infection that ultimately results into mortality. To reduce the impact of NCDs on COVID-19 cases, prevention is the best measure. Primary and secondary level prevention of NCDs plays a main role to control bad outcome in COVID-19 cases. The strategies that are required to address this comorbidity includes integration and convergence of the existing communicable and NCD programs, strengthening health care systems by giving major focus on primary health care services, health and wellness centers, universal health coverage, updating guidelines, enhancing community participation, capacity building, appropriate policy making, multi-sectoral participation and coordination.