The impact of salt consumption on cardiometabolic and cognitive health in aged female rats

doi:10.21203/rs.3.rs-4941682/v1

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The impact of salt consumption on cardiometabolic and cognitive health in aged female rats

https://doi.org/10.21203/rs.3.rs-4941682/v1

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published 25 Oct, 2024

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Health concerns about excess dietary salt have traditionally focused on its relationship with hypertension and the increased risk of cognitive impairment. However, research has often overlooked the unique health concerns and physiological differences between men and women, leading to gaps in knowledge, particularly regarding disease prevention and treatment strategies for women. The present study examined aged female rats over 12 weeks, using control, low, and high salt diets to mimic the post-menopausal phase in human females when cardiovascular risks typically increase. Cardiometabolic parameters and cognition were monitored. The findings revealed the impact of varying salt diets on blood lipids, blood pressure (BP) and heart rate (HR) levels and variability, anxiety, and cognition. Specifically, intake of a low-salt diet led to a significant reduction in BP levels but an increase in BP variability starting from the eighth week of the diet onset. Moreover, HR levels and variability were notably higher with the low-salt diet. Aged female rats exhibited increased anxiety on the low-salt diet at the fourth week, but the anxiety began to improve starting from the eighth week. Additionally, a trend suggested that the low salt intake worsened short-term memory while improving long-term memory. Furthermore, plasma lipids decreased significantly in aged female rats on a high-salt diet compared to those on a low-salt diet. The study provides valuable insights into the effects of salt intake on cardiometabolic parameters and cognitive function in aged female rats, highlighting the importance of considering sex-specific dietary guidelines for cardiometabolic and cognitive health.

Biological sciences/Neuroscience/Cognitive ageing

Biological sciences/Neuroscience/Cognitive neuroscience

Biological sciences/Neuroscience/Learning and memory

Biological sciences/Neuroscience/Neural ageing

Health sciences/Cardiology/Cardiovascular biology

Health sciences/Diseases/Cardiovascular diseases

Health sciences/Diseases/Metabolic disorders

Health sciences/Diseases/Neurological disorders

Health sciences/Health care/Disease prevention

Health sciences/Health care/Health policy

Health sciences/Health care/Nutrition

Health sciences/Health care/Public health

Health sciences/Medical research/Pre clinical studies

Health sciences/Neurology/Neurological disorders

Health sciences/Risk factors

dietary salt intake

aging

sex differences

cardiometabolic health

cognition

Salt is a common component of modern diets globally. The average global dietary salt intake is 12 g per day, approximately 2.5 times the recommended intake of 5 g per day. ^1,2 Excessive dietary salt intake has been associated with hypertension, and increased risk of cardiovascular disease and cognitive impairment.^3–5 However, the studies supporting this conclusion have notable limitations that cannot be overlooked. For instance, human studies lack a reliable method to accurately measure individual salt intake, and effective interventions to sustain low salt intake in free-living individuals, particularly with ethical concerns.^6,7 Animal studies have typically utilized exceptionally high-salt diets, containing 8 to 20 times more salt than the control, which may not be clinically relevant.^3,6 We previously reported that a clinically relevant high-salt diet did not significantly increase blood pressure (BP) levels nor its variability in both young and aged male rats.⁶ In contrast, a low-salt diet increased the survival ratio, decreased BP and its variability, and improved long-term memory in aged male rats.⁶

Moreover, the long-term impact of varying salt intakes on metabolism, BP, particularly BP variability (BPV), anxiety, and cognitive function remain inconclusive in aged female rats. Medical research has often overlooked the unique health concerns and physiological differences between men and women, leading to gaps in knowledge, especially concerning disease prevention and treatment strategies for women. This is particularly evident in cardiovascular and cerebrovascular diseases research, where it is increasingly recognized that women, especially post-menopausal women, have distinct cardiovascular and cerebrovascular risks compared to men.^8,9 Understanding these differences is critical for developing targeted prevention strategies and therapeutic interventions for women.

The aim of this study was to explore the comprehensive effects of dietary salt at clinically relevant dosages on cardiometabolic and cognitive health in aged female rats. Using aged female rat models in this study, which mimic post-menopausal women, helps to shed light on how dietary interventions may need to be tailored based on sex.

General parameters

During the dietary experiment, the body weights of all groups uniformly increased, as illustrated in Fig. 1. While rats on a low-salt diet had higher final body weights than those on control and high-salt diets, no significant differences were detected. Specifically, rats in the low-salt (0.1% NaCl) group weighed an average of 394 ± 15 g, those in the normal control salt (0.4% NaCl) group averaged 376 ± 16 g, and those in the high-salt (1% NaCl) group averaged 377 ± 22 g.

It is interesting to note that the consumption of dietary salt did not lead to any noticeable changes in blood sodium (Fig. 2A), blood potassium (Fig. 2B), sodium-to-potassium ratios (Fig. 2C), or blood glucose levels (Fig. 2D) across the groups. However, plasma lipid levels (Fig. 2E) were significantly lower in aged female rats that were on a high-salt diet compared to those on a low-salt diet. These findings suggest that a low-salt diet may affect the regulation of plasma lipid levels in aged female rats, while blood sodium, potassium, and glucose regulation remain unaffected.

BP and HR levels and variability

SBP (Fig. 3A), DBP (Fig. 3B), and MBP (Fig. 3C) all significantly declined starting from the eighth week in aged female rats on a low-salt diet. Furthermore, rats on a low-salt diet had significantly lower SBP (Fig. 3A), DBP (Fig. 3B), and MBP (Fig. 3C) levels compared to those on a high-salt diet or a control diet starting from the eighth week of the diet onset, but higher HR (Fig. 3D) levels at the eighth week.

In terms of BPV, low-salt diets increased the SD and CV of SBP (Figs. 3E, 3I), DBP (Figs. 3F, 3J), and MBP (Figs. 3G, 3K) compared to those on a high-salt diet or a control diet. They also increased the SD and CV of HR (Figs. 3H, 3L) compared to those on a control diet in aged female rats.

Anxiety and memory

The open-field test (Fig. 4) was used to assess anxiety behavior. Aged female rats on low-salt diets exhibited significantly less moving time (Fig. 4A) compared to the high-salt group at the fourth week. Additionally, moving distance (Fig. 4B), time spent in the center squares (Fig. 4C), and the number of grid crossings (Fig. 4D) were similar across the groups.

The novel object recognition test (Fig. 5A) was used to evaluate short-term memory, and a preference index—defined as the ratio of time spent with the novel object to total interaction time—was calculated.⁶ Rats on a low-salt diet had the lowest 24-hour (Fig. 5A) preference index at the twelfth week, although no significant differences were observed. For the assessment of long-term memory and learning capabilities, the spontaneous alternation ratio in a T-maze (Fig. 5B) was measured. Although the highest T-maze performance score was associated with a low-salt diet and the lowest score was associated with a high-salt diet, these differences were not statistically significant.

This investigation is the pioneering analysis of long-term dietary salt intake on metabolism, BP, BP variability, anxiety, and cognition in aged female rats. A high-salt diet, double the standard, was utilized to mirror clinically relevant excessive salt consumption and its effects were compared to a low-salt diet and a control diet. We observed the impact of varying salt diets on plasma lipids, levels and variability of BP and HR, anxiety, and cognition, but not body weights, blood glucose, blood sodium, and blood potassium. Specifically, intake of a low-salt diet led to a significant reduction in BP levels but an increase in BP variability starting from the eighth week of the diet onset. Moreover, HR levels and variability were notably higher with the low-salt diet. Furthermore, aged female rats were more anxiety with low-salt diets at the fourth week. However, the anxiety with low-salt diets was getting to improve starting from the eighth week, although no significant differences were detected. Moreover, there was a trend that low salt diets worsened the short-term memory while improved long-term memory. Furthermore, plasma lipids decreased significantly in aged female rats on high-salt diets compared to those on low-salt diets.

We previously found that high salt intake exerts broader systemic impacts on aged male rats, such as decreasing body weight and blood glucose levels.⁶ Contrarily, in this study, varying dietary salt did not influence body weights and blood glucose levels in aged female rats, suggesting that aged females may be less responsive to dietary salt compared to aged males regarding the abovementioned aspects. However, plasma lipid levels were significantly higher in aged female rats on a low-salt diet compared to those on a high-salt diet. Additionally, aged female rats had significantly higher plasma lipid levels than aged male rats,⁶ suggesting sex-specific lipids metabolic response to dietary salt. Moreover, blood sodium, potassium, and sodium-to-potassium ratio were similar across groups in aged female rats. Our previous study observed that a high-salt diet did not notably impact blood sodium levels in young adult male rats, but even a normal salt diet significantly elevated blood sodium levels in aged male rats.⁶ However, no discernible changes were identified in blood potassium levels or sodium-to-potassium ratios across the groups in male rats either.⁶ This implies that sodium regulation mechanisms may be compromised in aged male rats, but not in aged female rats. Furthermore, the absence of significant variations in blood potassium levels or sodium-to-potassium ratios across groups suggests that potassium regulation might be less sensitive to dietary salt in both sexes.

Numerous studies have demonstrated a strong correlation between high BP and excessive dietary salt intake.^6,10 Although elevated salt consumption can cause a temporary rise in BP, it appears to have minimal long-term effects.^6,11 This suggests potential compensatory mechanisms that might offset the short-term benefits of sodium reduction.^6,7 Furthermore, in our previous study, while young adult male rats showed an initial BP increase from a high-salt diet, this change was not significant and did not persist over time.⁶ Additionally, aged male rats did not experience significant BP increase with a high-salt diet, indicating that the impact of salt on hypertension may vary with age or other long-term factors.⁶

Clinical studies on sex differences in BP reveal that young women typically exhibit lower BP and muscle sympathetic nerve activity (MSNA) than young men.^12,13 In contrast, postmenopausal women often display higher BP and MSNA levels, alongside increased hypertension prevalence, compared to age-matched men.^12,13 This variance might be due to the reduced sensitivity to alpha-adrenergic receptors and an enhanced beta-adrenergic-mediated vasodilation in younger women, which declines post-menopause.^12,14,15 Consequently, older women exhibit higher peripheral resistance and hypertension rates. Research, such as the DASH-Sodium study, indicates that women experience more significant BP reductions with salt restriction than men.^12,16 Other studies show varied responses to salt intake, with some suggesting greater salt sensitivity in women, although findings are inconsistent.¹² In this research, it was observed that a high-salt diet did not elevate BP levels in aged female rats, paralleling results seen in aged male rats.⁶ Similarly, aged female rats on a low-salt diet demonstrated significantly reduced BP. These findings align with those in human females and in both young and aged male rats,⁶ indicating no sex-specific responses to salt-induced BP changes. However, our studies suggest that age may influence the effects of dietary salt on BP levels.

Furthermore, BPV refers to the fluctuations in BP over time and is emerging as a separate cardiovascular risk factor, independent of MBP levels.¹⁷ Higher variability has been linked to greater arterial stiffness and an increased risk of cardiovascular events and cognitive impairment.¹⁷ Research on the effects of dietary salt on BPV in women remains sparse, with most studies focusing on short-term rather than long-term BPV. Evidence indicate that men generally exhibit higher MBP, whereas women experience greater BPV.^18,19 For instance, a study involving 52,911 participants from Italian community pharmacies found that men had higher average 24-hour BP levels, while women showed greater variability.¹⁸ Another study revealed that while men displayed higher short-term BPV, it was not affected by dietary factors.²⁰ This difference in BPV may relate to age differences at the time of measurement, with one study beginning at age 14 and following up for 15 years, and another enrolling participant around 73.7 years old, well beyond the protective effects of estrogen in women.¹⁷

Our previous study showed that both high and low salt diets increased BPV in young adult male rats while a low-salt diet reduced BPV in aged male rats.⁶ In this study, we found that low-salt diets increased the BPV in aged female rats, which might be due to the greater BP reducing effect caused by low-salt diets. These findings suggest that salt restriction could potentially be beneficial for reducing BPV in aged male rats but not in aged female rats, indicating sex-dependent responses to salt restriction.

Moreover, the observed increase in HR among the aged female rats on low-salt diets may be due to the baroreflex. This rise in HR could be a compensatory mechanism to maintain cardiac output when blood volume is perceived to be lower. It may also reflect a shift in autonomic balance towards sympathetic predominance, as the body adjusts to a lower sodium state. Over time, as the body adapts to the low-salt diet, homeostatic mechanisms may recalibrate, leading to the normalization of HR.

The initial increase in anxiety levels associated with the low-salt diet could be linked to the stress response to a significant change in dietary intake. Sodium is known to play a role in the regulation of the stress response and behavior. Research has indicated that sodium restriction can be anxiogenic, leading to increased anxiety in both human and animal models.²¹ This reaction may be mediated by the renin-angiotensin-aldosterone system (RAAS), which is sensitive to changes in sodium balance. It is also possible that dietary sodium could affect brain neurotransmitter levels,²² which are involved in the regulation of mood and anxiety. Interestingly, the study suggests that by the eighth week, anxiety levels began to decrease in the low-salt diet group. This improvement could indicate a habituation effect, where the initial stress response diminishes as the body and brain become accustomed to the new dietary environment. It aligns with the concept of neuroplasticity, where the brain's structure and function can change in response to environmental factors, including diet.²³

The impact of dietary salt intake on cognitive functions in humans has been primarily studied through longitudinal investigations in aging populations, with varied results. For example, a three-year prospective study of 1,262 adults aged 67 to 84 found that reduced salt consumption at baseline was associated with enhanced cognitive function.^6,24 Notably, this relationship was only observed in participants with lower levels of physical activity at baseline, and there was no correlation between salt intake and cognitive function in more active individuals. Conversely, two prospective studies found no link between dietary salt intake and cognitive decline. The first study by Nowak et al.²⁵ included 1,194 adults with a mean age of 74 ± 3 years and a follow-up period of 6.9 years, while the second study by Haring et al. ²⁶ included 6,426 women aged 65 to 79 with a median follow-up of 9.1 years. The latter study particularly noted that salt intake did not affect the risk of cognitive impairment in hypertensive women, suggesting a possible indirect effect of salt on cognition through vascular function changes.⁶

While findings from human studies have varied, most animal studies have consistently demonstrated negative cognitive effects from a high-salt diet.⁶ However, these studies primarily focus on young-adult male animals subjected to extremely high-salt diets.^3,6 It is important to note that these animal studies implemented exceptionally high levels of salt intake, ranging from 8 to 20 times higher than a normal salt diet, limiting the applicability of these findings to clinical settings.⁶

In our previous findings, we observed that both high- and low-salt diets did not have any significant influence on short-term or long-term memory in young adult male rats.⁶ In contrast, aged male rats exhibited a decrease in short-term memory but showed an enhancement in long-term memory when subjected to either control or low-salt diets. The high-salt diet had no noticeable impact on short-term memory but resulted in impairment in long-term memory in aged male rats.⁶

In this study, we found that a low-salt diet may lead to decreased short-term memory but improved long-term memory in aged female rats, aligning with our previous research in aged male rats.⁶ This trend suggests that dietary salt could play an important role in the brain's ability to form and retain long-term memories, which has profound implications for human health, especially as it pertains to aging and the risk of cognitive decline. Cognitive decline is a major concern in aging populations, often leading to conditions such as dementia and Alzheimer's disease. Memory impairment is a hallmark of these conditions, deeply affecting the quality of life.

The implications of a low-salt diet on long-term memory enhancement observed in the study could suggest a protective or restorative effect of reduced sodium intake against cognitive decline. This finding adds to the narrative that modifiable lifestyle factors, such as diet, play a crucial role in the maintenance of cognitive health. It provides a promising avenue for non-pharmacological intervention strategies that could be implemented to mitigate the risks of age-related cognitive disorders. Furthermore, the study's implications extend beyond the sphere of individual health and into public health policy and dietary recommendations. With the growing evidence that diet can significantly impact cognitive functions, there is a clear need for guidelines that consider the neuroprotective potential of dietary choices.²⁷ Such guidelines could be particularly beneficial for populations already at risk of cognitive decline, such as the elderly or those with a family history of neurodegenerative diseases.

To the best of our knowledge, our research is among the first to investigate the long-term effects of varying levels of dietary salt on metabolism, cardiovascular, and cognitive health in aged female rats. Our study followed rigorous methodological standards, including randomized assignment, double-blind procedures, and video-recorded behavioral assessments. Nonetheless, the findings should be interpreted within the context of the study's limitations. A significant limitation is the lack of insights into the potential mechanisms that may explain the observed sex-specific effects of salt intake on the relationship between metabolism, cardiovascular, and cognitive function in aged female and male rats.

Sodium restriction has been shown to reduce sympathetic vascular transduction.²⁸ The autonomic profile of women is characterized by a reduced sympathetic influence on BP, which is partially mediated by estrogen.^20,29 Women's sympathetic nerves have a decreased ability to induce vasoconstriction, likely due to augmented beta-adrenergic vasodilator effects compared to men.^20,30 Estrogen attenuates the RAAS, shifting the pressure-natriuresis curve to the left and decreasing BP.²⁰ This sex difference may also be influenced by changes in neuronal nitric oxide synthase (NOS), as NOS inhibitors allow greater BP increase in response to angiotensin II in females, while having no effect in males.^31,32 Estrogen also reduces endothelin levels, which promotes renal vasoconstriction and sodium absorption.³²

Moreover, gut microbiota dysregulation was strongly associated with 24-hour ambulatory BP in women but not men, which may be mediated through propionic acid³³ and arachidonic acid.³⁴ The immune system also contributes to sex differences in hypertension. Regulatory T cells protect against the development of hypertension and are particularly important for BP control in females.³⁵ Testosterone affects BP differently in men and women. High testosterone levels have been associated with increased BP in post-menopausal women,³⁶ while the reverse trend is observed in men.^32,37 The mineralocorticoid receptor-renal epithelial Na⁺ channel axis is the primary determinant of excessive renal sodium reabsorption and an attractive antihypertensive target in female rats with angiotensin II-induced hypertension, but not in males.³⁸ Thus, future research should aim to examine the prospective mechanisms underlying these sex differences.

Overall, this study contributes to a better understanding of how dietary choices, particularly salt intake, can have multifaceted effects on metabolism, cardiovascular, and cognitive function in aged female rats. Our study emphasizes the need for a greater understanding of sex differences in cardiovascular disease and cognitive decline risk factors and the development of tailored strategies for prevention and treatment. It also highlights the value of using female animal models in research to better understand the unique cardiometabolic and cognitive health challenges faced by women, especially after menopause.

Animals and diets

Aged female Sprague-Dawley (SD) rats (22–24 months old) were purchased from Slac Laboratory Animal (Shanghai, China) and housed in standard cages in a temperature-controlled facility with 12 h light/dark cycle. As previously described,⁶ all animal experiments were approved by the Research Ethics Committee of Hangzhou Normal University (Approval reference# HSD20211205). All methods were performed in accordance with the relevant guidelines and regulations. The animal experimental procedures followed the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and the authors complied with the ARRIVE guidelines. Rats received tap water ad libitum and normal control (0.4% NaCl), low-salt (0.1% NaCl), or high-salt (1% NaCl) chow from Xietong Biotechnology Co. (Hangzhou, China) for 12 weeks. Animals were assigned randomly to the experimental groups. Animals were anesthetized with 2.5% isoflurane via a mask. Animals underwent euthanasia by CO2, followed by decapitation via a guillotine. Data was collected and processed randomly. The individuals conducting the experiment measurements were blinded to group allocation. The person assessing, measuring, or quantifying the experimental outcomes were blinded to the intervention.

Blood pressure and heart rate measurements

As previously described,⁶ systolic BP (SBP), diastolic BP (DBP), mean BP (MBP), and heart rate (HR) were measured repeatedly using a noninvasive pressure device, ALC-NIBP (Alcott Biotech, Shanghai, China), at baseline and then biweekly after the onset of the diet. Measurements were obtained in conscious rats restrained in a thermal plastic chamber. The standard deviation (SD) and coefficients of variation (CV) (SD*100/mean, %) were calculated to assess the variability of SBP, DBP, MBP, and HR.

Behavioral tests

Anxiety (open-field test), short-term memory (novel object recognition), and long-term memory (T-maze) were measured repeatedly at baseline, and then 4, 8, and 12 weeks after the onset of the diet.

Apparatus

As previously described,⁶ an open black box (100 x 100 x 40 cm, long x wide x high) was used for both the open-field test and the novel object recognition test. Two distinct objects were additionally added to the novel object recognition test. The spontaneous alternation task was conducted in a modifiable T-maze. The maze was made of black plastic, with floors 15 cm wide and walls 40 cm high. The stem was 75.5 cm long and the cross piece was 136 cm long. All behavioral tests were videotaped.

Procedure

Open-field test

Transport the animals to the testing room 1 h prior to the testing to allow them to acclimate to the environment. The experimental room should be isolated from sound and unintentional interruptions. Place the animal in the open field for 5 min. Total distance moved, time spent moving, time spent in the center squares, and number of squares crossed were measured.³⁹

Novel Object Recognition

As previously described,⁶ the animals were handled for 3 days during the acclimation period before the initial test. In the training trial, the animals explored two identical objects (A1 and A2) for 10 minutes. The animals were then returned to their home cages for 1 hour. In the testing trial, the animals explored a familiar sample object (A) and a novel object (B) for 5 minutes. Object exploration includes any direct contact with the mouth, nose, or paw, and should not include accidental contact, such as bumping into the object while passing. The training and testing trials were videotaped for subsequent measurement and analysis of object exploration by an individual blinded to the experimental condition. A discrimination ratio (novel object interaction/total interaction with both objects) was calculated.

T-maze

The spontaneous alternation task allows free choice of goal arm during both the sample and choice trials. As previously described,⁶ the animal was placed in the start area and allowed to choose a goal arm. Then, the animal was gently removed and replaced in the start area. The animal was then allowed to choose between two open goal arms. Five trials were performed, and a percentage per animal was calculated.

Physiology parameters

As previously described,⁶ physiological variables including sodium (Na⁺), potassium (K⁺), the sodium-to-potassium ratio, and glucose, were measured at the endpoint using an i-STAT portable clinical analyzer (Abott, IL, US) and EC8 + cartridge (Abott, IL, US).

Blood lipids determination by enzyme-linked immunosorbent assay (ELISA)

As previously described,⁶ blood lipids were measured using a lipids ELISA kit (Baiyi Bio, Shanghai, China). Plasma was collected using EDTA anticoagulant tubes and was centrifuged for 30 minutes at 3000xg at 4˚C. Briefly, standards and samples was added following by lipids HRP-conjugate reagent and were incubated for 60 minutes at 37 ˚C. Each well was aspirated and washed for five times. Chromogen solution A and B were added, then gently mixed and incubated for 15 minutes at 37 ˚C (protect from light). Stop solution was added and absorbance at 450 nm was measured with an automated microplate reader. Lipids concentrations were expressed as mmol/L. All samples were performed in triplicate.

Statistical Analysis

All statistical analyses were performed using Prism 9 (GraphPad). All values were expressed as mean ± SEM. Data was analyzed using one-way or two-way ANOVA with Tukey’s post-tests. The alpha level was set at 0.05 for all analyses.

Competing interests

The authors declare no competing interests.

Author Contribution

Conceptualization, Fen Sun and Jing-Hua Wang; Data curation, Fen Sun, Lu-Ping Zhao, Qi Jin, Qiu-Xiang Wang, Shi-Han Jin, Ji-Zhi Xie, Jun-Tao Xu, Meng-Jia Yin and Chao Jin; Formal analysis, Fen Sun, Lu-Ping Zhao, Qi Jin, and Jing-Hua Wang; Funding acquisition, Fen Sun and Jing-Hua Wang; Investigation, Fen Sun, Lu-Ping Zhao, Qi Jin, Qiu-Xiang Wang, Shi-Han Jin, Ji-Zhi Xie, Jun-Tao Xu, Meng-Jia Yin and Chao Jin; Methodology, Fen Sun, Lu-Ping Zhao, Qi Jin, Qiu-Xiang Wang, Shi-Han Jin, Ji-Zhi Xie, Jun-Tao Xu, Meng-Jia Yin, Chao Jin, and Jing-Hua Wang; Project administration, Fen Sun and Jing-Hua Wang; Resources, Fen Sun and Jing-Hua Wang; Supervision, Fen Sun and Jing-Hua Wang; Validation, Fen Sun, Lu-Ping Zhao, Qi Jin, Ji-Zhi Xie, Jun-Tao Xu, Meng-Jia Yin, Chao Jin, and Jing-Hua Wang; Visualization, Fen Sun and Jing-Hua Wang; Writing – original draft, Fen Sun; Writing – review & editing, Fen Sun and Jing-Hua Wang.

Acknowledgments

This work was supported by the Start-up Funding of Hangzhou Normal University (4255C50221204123), the Hangzhou Youth Innovation Team Project (TD2023020), Ministry of Education's China University Industry Research Innovation Fund (2022BC025), Hangzhou Biomedical and Health Industry Development Support Science and Technology Special Project (2021WJCY136, 2021WJCY285, 2022WJC199), and Zhejiang Medical Association Clinical Medical Research Special Fund Project (2022ZYC-Z29). We extend our sincere gratitude to the entire staff of the Laboratory Animal Facility at Hangzhou Normal University for their invaluable support and assistance.

Data Availability

The analyzed data is available from the corresponding author on reasonable request.

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No competing interests reported.

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The impact of salt consumption on cardiometabolic and cognitive health in aged female rats

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Journal Publication

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Abstract

Figures

Introduction

Results

General parameters

BP and HR levels and variability

Anxiety and memory

Discussion

Methods

Animals and diets

Blood pressure and heart rate measurements

Behavioral tests

Apparatus

Procedure

Open-field test

Novel Object Recognition

T-maze

Physiology parameters

Blood lipids determination by enzyme-linked immunosorbent assay (ELISA)

Statistical Analysis

Declarations

Competing interests

Author Contribution

Acknowledgments

Data Availability

References

Additional Declarations

Status:

Journal Publication

Version 1