A High-Salt Diet Further Impairs Age-Associated Declines in Cognitive, Behavioral, and Cardiovascular Functions in Male Fischer Brown Norway Rats

Chugh, Gaurav; Asghar, Mohammad; Patki, Gaurav; Bohat, Ritu; Jafri, Faizan; Allam, Farida; Dao, An T.; Mowrey, Christopher; Alkadhi, Karim A.; Salim, Samina

doi:10.3945/jn.113.177980

Cited by 33 publications

(38 citation statements)

References 85 publications

(122 reference statements)

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“…In the same study, it was reported that the central administration of AT1 receptor blocker or tempol reduces the BP in sodium-sensitive rats more than in salt-resistant rats, which suggests that AngII-induced enhancement of central oxidative stress may be due to the sodium sensitivity. Also, salt loading caused an increase in hypothalamic mRNA expression subunits of NADPH oxidase p22, gp91, and p47 in Dahl sodium-sensitive rats [46] and unchanged MnSOD and Cu/ZnSOD levels in hippocampus and amygdale of FBN rats [47] and these findings support the suggestions mentioned above. Consistently, results of this study showed that HS diet in older rats significantly increased the hypothalamic gp91 protein, p22 mRNA levels compared with the young rats without altering the hypothalamic antioxidant levels and similarly, HS diet increased the NADPH oxidase activity more in the old rats.…”

Section: Discussionsupporting

confidence: 79%

Effect of High-Salt Diet on Age-Related High Blood Pressure and Hypothalamic Redox Signaling

Başgut

Whidden²,

Kirichenko³

et al. 2017

Pharmacology

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Aim: The aim of this study was to investigate the effect of a high salt (HS) diet on age-related changes in blood pressure (BP) and the possible role played by regulatory central mechanisms. Methods: Young (5 months) and old (27 months) male Fischer 344 × Brown Norway (F344/BN) rats were fed standard chow or 8% HS diet for 12 days. BP and heart rate (HR) were measured by telemetry. Results: Mean arterial BP (MAP) was significantly elevated in old rats during the day and night when compared with young animals. The HS diet further elevated MAP in both age groups, and the increase was more pronounced in the old animals, while HR was not altered by age or HS diet. In addition, cardiovascular responses to restraint stress were diminished in the old when compared with the young and were unchanged with HS diet in either age group. Both age and the HS diet elevated the adrenomedullary mRNA levels of tyrosine hydroxylase, an indicator for sympathoexcitation. HS diet enhanced intracerebroventricular angiotensin II (AngII)-induced BP and HR elevations in both age groups. AngII type 1 receptor mRNA increased significantly in the hypothalamus with age and HS diet. Furthermore, hypothalamic p22^phox mRNA and gp91^phox protein, subunits of NADPH oxidase, as well as NADPH oxidase activity increased with the HS diet in the old animals, whereas antioxidant enzymes that decreased with age yet remained unaltered with the HS diet. Conclusion: Our findings indicate that sensitivity of BP to HS diet increases with age, and that central AngII-induced pressor responses are diminished in old rats compared with the young both under control conditions and during HS diet treatment. These changes are paralleled by increases in the expression and NADPH oxidase activity in the hypothalamus, possibly leading to central oxidative stress-mediated sympathoexcitation and high BP.

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Section: Discussionsupporting

confidence: 79%

Effect of High-Salt Diet on Age-Related High Blood Pressure and Hypothalamic Redox Signaling

Başgut

Whidden²,

Kirichenko³

et al. 2017

Pharmacology

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“…As the population ages, identifying modifiable lifestyle factors that promote healthy cognitive aging is an increasingly pressing public health concern (2). Dietary sodium intake is one lifestyle factor that may affect cognitive function (3, 4), but its role in cognitive aging has not been thoroughly studied (5, 6). …”

Section: Introductionmentioning

confidence: 99%

“…Dietary sodium intake may also impair cognitive function independently of its effect on blood pressure. For example, studies in rodents (3, 4) suggest that high sodium diets impair spatial memory through an increase in oxidative stress in the hippocampus.…”

Section: Introductionmentioning

confidence: 99%

Association between dietary sodium intake and cognitive function in older adults

Rush

Kritz‐Silverstein

Laughlin

et al. 2017

The Journal of nutrition, health and aging

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OBJECTIVES To examine the association of dietary sodium intake with cognitive function in community-dwelling older adults. DESIGN Cross-sectional study SETTING Southern California community PARTICIPANTS White men (n=373) and women (n=552), aged 50–96 years from the Rancho Bernardo Study, a longitudinal study of cardiovascular disease risk factors and healthy aging. MEASUREMENTS During the 1992–1996 research clinic visit, a food frequency questionnaire was used to determine daily sodium intake; cognitive function was assessed with Trails Making Test, part B (Trails B), Mini-Mental State Exam (MMSE), and Verbal Fluency Test (VFT); and medical, clinical and demographic information was obtained. Linear regression was used to assess the association between calorie-adjusted sodium intake and cognitive test scores with adjustment for demographic, behavioral and health measures. Logistic regression examined the odds of having cognitive impairment by sodium intake. RESULTS Lower sodium intake was associated with poorer performance on Trails B (p=0.008) and MMSE (p=0.003) after controlling for age, sex, and education. Associations did not differ by sex, but there was a significant interaction by age for the Trails B: older (≥80 years), but not younger, adults showed worse performance with lower sodium intake (p=0.03). Associations remained significant after additional adjustment for smoking, alcohol intake, exercise, body weight, cardiovascular risk factors, kidney function, diuretic medication use, and diet quality. Lower daily sodium intake was associated with increased odds of cognitive impairment on the MMSE (score < 26; OR per SD decrease = 1.12, 95% CI 1.08, 1.16). CONCLUSION Lower sodium intake was associated with worse cognitive function in older community-dwelling adults. For the maintenance of cognitive health, older adults may be advised to avoid very low sodium diets.

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“…Chugh et al (16) showed in young (2 mo) and old (20 mo) male Fischer 344/BN rats that a HS (8% NaCl) diet for 4 wk increased systolic blood pressure by Ͻ5 mmHg. Therefore, it is unlikely that the age-associated effects were due to hypertension.…”

Section: Discussionmentioning

confidence: 98%

“…To maximize the sodium load, we maintained the rats on a LS diet for 2 wk before transferring them to a HS diet. We chose the Fischer 344/BN rat to avoid the confounds of age-and sodium-induced hypertension since these animals remain normotensive throughout their lifespan (7) and their blood pressure increases only marginally on a HS diet (16).…”

mentioning

confidence: 99%

Aging-related impairment of urine-concentrating mechanisms correlates with dysregulation of adrenocortical angiotensin type 1 receptors in male Fischer rats

Zheng

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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To investigate age-associated impairments in fluid homeostasis, 4-mo (young) and 32-mo (old) Fischer 344/BN male rats were studied before and after a dietary sodium load. Transferring young rats from a low-sodium (LS) to a high-sodium (HS) diet increased water intake and urine volume by 1.9- and 3.0-fold, respectively, while urine osmolality and plasma aldosterone decreased by 33 and 98%. Concomitantly, adrenocortical angiotensin type 1 receptor (AT1R) density decreased by 35%, and AT1bR mRNA decreased by 39%; no changes were observed in AT1aR mRNA. In contrast, the increase in water intake (1.4-fold) was lower in the old rats, and there was no effect of the HS diet on urine volume or urine osmolality. AT1R densities were 29% less in the old rats before transferring to the HS diet, and AT1R densities were not reduced as rapidly in response to a HS diet compared with the young animals. After 6 days on the HS diet, plasma potassium was lowered by 26% in the old rats, whereas no change was detected in the young rats. Furthermore, while plasma aldosterone was substantially decreased after 2 days on the HS diet in both young and old rats, plasma aldosterone was significantly lower in the old compared with the young animals after 2 wk on the LS diet. These findings suggest that aging attenuates the responsiveness of the adrenocortical AT1R to a sodium load through impaired regulation of AT1bR mRNA, and that this dysregulation contributes to the defects in water and electrolyte homeostasis observed in aging.

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A High-Salt Diet Further Impairs Age-Associated Declines in Cognitive, Behavioral, and Cardiovascular Functions in Male Fischer Brown Norway Rats

Cited by 33 publications

References 85 publications

Effect of High-Salt Diet on Age-Related High Blood Pressure and Hypothalamic Redox Signaling

Effect of High-Salt Diet on Age-Related High Blood Pressure and Hypothalamic Redox Signaling

Association between dietary sodium intake and cognitive function in older adults

Aging-related impairment of urine-concentrating mechanisms correlates with dysregulation of adrenocortical angiotensin type 1 receptors in male Fischer rats

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